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1.
AIM: To investigate the role of hydrogen sulfide (H2S) in the protection against oxidative stress in rats with chronic obstructive pulmonary disease (COPD).METHODS: The rat model of COPD was established by cigarette smoking (CS) combined with lipopolysaccharide (LPS) instillation. Thirty-two healthy male Sprague-Dawley rats were randomly divided into 4 groups: control group, CS+LPS group, CS+LPS+NaHS (H2S donor) group and CS+LPS+PPG (DL-propargylglycine, an inhibitor of cystathionine-γ-lyase) group. After 30 days, the lung functions of the rats were measured, the histological changes of lungs were observed under light microscope and the pathological scores were calculated. The H2S level in plasma and the protein expression of cystathionine-γ-lyase (CSE) in the lung tissues were measured. The content of malondialdehyde (MDA), the activity of superoxide dismutase (SOD) and catalase (CAT) were detected to reflect oxidative stress.RESULTS: Compared with control group, the peak expiratory flow (PEF) decreased by 24% and intra-pressure (IP) increased by 66% in CS+LPS group. The pathological scores of the lung tissues also increased. Compared with CS+LPS group, no change in the lung function was observed after given NaHS or PPG, but the pathological scores decreased in CS+ LPS+ NaHS group. Compared with control group, the content of H2S in plasma was increased by 26% on day 16. Compared with CS+LPS group, the content of H2S in plasma of CS+LPS+PPG group was decreased by 22% after 30 days. Compared with control group, the protein expression of CSE increased, and no statistical difference among CS+LPS group, CS+ LPS+ NaHS group and CS+LPS+PPG group was observed. Compared with control group, MDA content in the lung tissues was increased by 24% in CS+LPS group, the activity of SOD was increased by 47% and the activity of CAT was increased by 52%. Compared with CS+LPS group, the MDA content in CS+LPS+NaHS group was decreased by 21%, and no statistical difference in the activity of SOD and CAT was observed. The activity of SOD decreased by 33% after given PPG.CONCLUSION: H2S plays a role as anti-oxidant in the rats with COPD. The CSE/ H2S pathway may be involved in the development of COPD.  相似文献   

2.
AIM: To explore the effects of hydroxylamine on the pulmonary arterial pressure in chronic hypoxic hypercapnic rats. METHODS: Twenty-four male Sprague-Dawley rats were randomly divided into 3 groups (8 rats in each group): the normal control group (NC), hypoxic hypercapnia+normal saline group (NS), hypoxic hypercapnia+hydroxylamine group (HA). The animals in NS and HA groups were kept in the O2 (9%-11%) and CO2 (5%-6%) cabin, 8 h a day and 6 days a week for 4 weeks. Before entering the cabin, the rats in HA group were administered with 1 mL hydroxylamine (12.5 mg/kg) by intraperitoneal injection, while the rats in NS group were given intraperitoneal injection of 1 mL saline solution. The mean pulmonary arterial pressure (mPAP) was measured by external jugular vein cannulation. The heart was removed, and the right ventricle (RV) and the left ventricle plus the septum (LV+S) were dissected. The ratio of the wet weight of the RV to that of the LV+S was calculated. The changes of the pulmonary vascular construction were observed under optical microscope. The concentration of H2S in the plasma was measured with a spectrometer. The expression of cystathionine-γ-lyase (CSE) in the pulmonary arterioles and bronchi was measured by immunohistochemistry and RT-PCR. RESULTS: The values of mPAP, RV/(LV+S),vessel wall area/total area (WA/TA) and media thickness of pulmonary arterioles (PAMT) in NS group and HA group were significantly higher than those in NC group (P<0.05). The level of H2S in the plasma, the content of CSE protein and the expression of CSE mRNA in NC group were significantly lower than those in NS group (P<0.05). The values of mPAP, RV/(LV+S), WA/TA and PAMT in HA group were significantly lower than those in NS group (P<0.05). The level of H2S in the plasma, the content of CSE protein and the expression of CSE mRNA in HA group were significantly higher than those in NS group (P<0.05). CONCLUSION: Hydroxylamine may decrease the pulmonary arterial hypertension induced by chronic hypoxic hypercapnia in rats by increasing the level of H2S in the plasma, the content of CSE protein and the mRNA expression of CSE, thus improving the pulmonary vascular structural remodeling.  相似文献   

3.
AIM: To investigate the role of hydrogen sulfide (H2S) in the cholecystokinin octapeptide (CCK-8) attenuating lipopolysaccharide (LPS)-induced lung injury. METHODS: A rat model of lung injury induced by intravenous injection of LPS was developed. Male Wistar rats were divided into normal control group, LPS group, LPS+CCK-8 group and CCK-8 group. Six hours after LPS injection, partial pressure of oxygen in the arterial blood (PaO2), H2S content and cystathionine-γ-lyase (CSE) activity in lung tissue were detected. The mRNA expression of CSE in lung tissue was determined by RT-PCR; the structure of lung tissues was observed under optical microscope. RESULTS: Compared to normal control rats, the LPS-treated rats had significantly decreased PaO2 level, increased index of quantitative assessment (IQA) score, while H2S content, CSE activity and the mRNA expression of CSE in lung tissue were significantly increased (all P<0.05). Administration of CCK-8 into LPS-treated rats increased the PaO2 level and alleviated the degree of lung injury (measured by IQA score). In addition, CCK-8 decreased H2S content, CSE activity, and the mRNA expression of CSE (all P<0.05). No significant difference of the above-mentioned parameters between CCK-8 group and normal control group was observed. CONCLUSION: CCK-8 reduces LPS-induced lung injury through inhibiting the generation of endogenous H2S.  相似文献   

4.
AIM:To investigate the mechanisms by which bilirubin inhibits acute lung injury (ALI). METHODS:30 female Wistar rats were divided into normal group, ALI group and bilirubin treatment group. ALI was induced by intravenous injection of LPS. The contents of OH-, H2O2 and O2· in the lung as well as the expression of caspase-3 in the lungs were investigated. RESULTS:(1) The contents of OH-, H2O2 and O2· in the lung homogenate and the expression of caspase-3 in the lungs in ALI group increased compared with those in normal group (P<0.05). (2) The contents of OH-, H2O2 and O2· in the lung homogenate and the expression of caspase-3 in the lungs in bilirubin treatment group increased compared with those in normal group, but decreased compared with those in ALI models (P<0.05). CONCLUSION:(1) Bilirubin was shown to be able to ameliorate apoptosis in ALI rats. (2) The increase in the contents of OH-, H2O2, O2· in ALI group indicated the development of oxidative lung injury, which was ameliorated by bilirubin. (3) Expression of caspase-3 confirmed that the model made by LPS was associated with apoptosis, which was reduced by bilirubin.  相似文献   

5.
AIM: To explore the role of endogenous and exogenous hydrogen sulfide (H2S) in acute lung injury (ALI) induced by ischmia-reperfusion (IR) of hind limbs in rats.METHODS: A Sprague-Dawley rat model of acute lung injury was induced by ischemia of the hind limbs for 4 h and reperfusion for another 4 h. The rats (n=120) were randomly divided into 4 groups: control, IR, NaHS (H2S donor)+IR, and propargylglycine +IR. The animals were sacrificed after reperfusion. Lung weight/body weight ratio (LW/BW) was measured and calculated. Morphological changes of the lung tissues were observed. The concentrations of H2S, nitric oxide (NO) and carbon monoxide (CO) in plasma were tested. The content of malondialdehyde (MDA), the activity of CSE, inducible nitric oxide synthase (iNOS) and hemeoxygenase (HO) in the lungs were determined. The polymorpho-nuclear neutrophils(PMN) and protein content in bronchoalveolar lavage fluid(BALF) were also measured. The correlation of H2S content with the above indices was analyzed.RESULTS: Compared with control group, severe injuries of the lung tissues, raised LW/BW, MDA concentration, PMN and protein contents in BALF were observed in IR group. Limb IR also made a drop in the concentration of plasma H2S and the activity of lung CSE, while the activity of iNOS and HO in the lung tissues and the levels of plasma NO and CO increased. Administration of NaHS before IR attenuated the changes induced by IR, while pre-administration of PPG exacerbated the IR injuries and increased the plasma NO level and lung iNOS activity. The H2S content was positively correlated with CSE activity, CO content and HO-1 activity (P<0.01), and negatively correlated with the other indices (P<0.01).CONCLUSION: Down-regulation of H2S/CSE is involved in the pathogenesis of acute lung injury induced by IR. Endogenous and exogenous H2S protects against lung injuries. The anti-injury effects of H2S are related with its anti-oxidative activity to attenuate the inflammatory over-reactions in the lung induced by PMN. Down-regulation of NO/iNOS system and up-regulation of CO/HO-1 system by H2S are also involved in the process of anti-injury to ALI.  相似文献   

6.
AIM: To investigate the effect of H2S on pulmonary artery hypertension during acute lung injury induced by LPS and the interaction between the systems of hydrogen sulfide (H2S)/cystathionine-β-lyase (CSE) and nitric oxide (NO)/nitric oxide synthase (NOS) in this process. METHODS: Seventy-two adult male rats were randomly divided into four groups: control group, LPS group, LPS+L-NAME group and LPS+propargylglycine (PPG) group. Mean pulmonary artery pressure (mPAP) of each rat was examined at 2 h, 4 h, 6 h and 8 h after treatment. H2S and NO contents in plasma, NO content, iNOS, cNOS and CSE activity in lung were measured at 4 h or 8 h after treatment, respectively. Expression of iNOS in lung tissue was also detected by immunohistochemistry technique, and the injury of lung was evaluated with morphological changes under microscope. RESULTS: LPS could induce severe lung injury, and mPAP, NO content, iNOS activity and its protein expression in LPS group significantly increased, but cNOS activity, H2S content and CSE activity decreased compared with those of control group. Administration of L-NAME before LPS could attenuate the changes induced by LPS. Pre-administration of PPG, a CSE inhibitor, exacerbated the injury by LPS, but there was no prominent variation in cNOS activity. CONCLUSION: Reduced endogenous H2S could increase pulmonary artery hypertension during acute lung injury induced by LPS. There is a negative effect between H2S/CSE system and NO/NOS system in this process.  相似文献   

7.
AIM: To study the role of heme oxygenase (HO)-1 in the mechanism of cholecystokinin-octapeptide (CCK-8) for attenuation of acute lung injury (ALI) induced by lipopolysaccharide (LPS).METHODS: Adult male rats were randomly divided into five groups: control group,LPS group,CCK-8+LPS group,LPS+ Hm (hemin,HO-1 donor) group and LPS+ZnPP (zinc protoporphyrin,specific inhibitor of HO-1) group.PMN number in bronchoalveolar lavage fluid (BALF),the structure of the lung,MDA content,HO-1 activity,the expressions of HO-1 mRNA and protein in the lung were detected respectively.RESULTS: The lung injury in LPS group was observed,at the same time the numbers of PMN,the content of MDA,the activity and the expression of HO-1 were all higher than those in control group (all P<0.05).The degree of lung injury,PMN numbers and MDA content were lower,while the activity and the expression of HO-1 in CCK-8+LPS and LPS+Hm group were higher than those in LPS group (all P<0.05).However,the degree of lung injury,PMN numbers and MDA content were higher,the activity and the expression of HO-1 were lower in LPS+ZnPP than those in LPS group respectively (all P<0.05).CONCLUSION: CCK-8 attenuates the LPS-induced ALI by means of anti-oxidation and inhibits PMN aggregation,which are both mediated by HO-1 partly.  相似文献   

8.
AIM：To investigate the role of hydrogen sulfide (H2S) in alleviation of liver injury by mesenteric lymph drainage in hemorrhagic shock rats. METHODS：A hemorrhagic shock model was established in male Wistar rats. DL-propargylglycine (PPG), an inhibitor of cystathionine γ-lyase (CSE) which is a synthase of H2S, or sodium hydrosulfide (NaHS), a donor of H2S, was administered to the hemorrhagic shock rats with mesenteric lymph drainage. The rats were randomly divided into sham, shock, shock+drainage, shock+drainage+PPG (45 mg/kg, ip, 0.5 h before hemorrhage) and shock+drainage+NaHS (28 μmol/kg, ip, 0.5 h before hemorrhage) groups. Fluid resuscitation was performed 1 h after hypotension, and then mesenteric lymph was drained in the rats of shock+drainage, shock+drainage+PPG and shock+drainage+NaHS groups for 3 h. The hepatic histomorphology was observed. The biochemical indexes of hepatic function in plasma, and H2S, CSE, Toll-like receptor 4 (TLR4), interleukin (IL)-10, IL-12 and tumor necrosis factor α (TNF-α) in hepatic homogenate were also examined. RESULTS：The levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total bile acid (TBA) in plasma, and H2S, CSE, TLR4, IL-10, IL-12 and TNF-α in hepatic homogenate in shock group were significantly higher than those in sham group. Mesenteric lymph drainage obviously reduced these indexes in shock rats, except for TLR4. PPG further decreased these indexes except for CSE, while NaHS increased these indexes except for TBA and CSE. Morphological observation showed that liver injury appeared in the rats from shock and shock+drainage+NaHS groups, and there was nearly normal hepatic structure in the rats from sham, shock+drainage and shock+drainage+PPG groups. CONCLUSION：The mechanism of mesenteric lymph drainage alleviating liver injury in hemorrhagic shock rats is related to reducing the production of H2S and alleviating the H2S-mediated inflammation.  相似文献   

9.
AIM: To study the role of carbon monoxide (CO) in the mechanism of cholecystokinin-octapeptide (CCK-8) for attenuation of acute lung injury (ALI) induced by lipopolysaccharide (LPS). METHODS: Fifty-six adult male rats were randomly divided into seven groups: control group, LPS group, LPS+ZnPP (a specific inhibitor of HO-1) group, LPS+Hemin (Hm， CO donor) group, CCK-8+LPS group, CCK-8+LPS+ZnPP group and CCK-8 group (n=8 for each). Bronchoalveolar lavage was performed 2 h, 6 h and 12 h respectively after treatments. The numbers of polymorphonuclear leukocytes (PMN) in bronchoalveolar lavage fluid (BALF) was detected. The mortality of rats and the structure of lung tissues were observed. MDA and CO contents in lung tissues were also measured. RESULTS: The mortalities of rats were both zero 2 h and 6 h after agent administration. The mortality of rats was higher than control group 12 h after LPS administration. The mortality of rats in LPS+Hm and CCK-8+LPS group were lower than that in LPS group, and its in LPS+ZnPP and CCK-8+LPS+ZnPP group were lower than that in LPS and CCK-8+LPS group, respectively. Lung injury was observed in LPS group. At the same time the number of PMN, MDA and CO content were higher than those in control group. The degree of lung injury, PMN numbers and MDA content were lower, while CO content in LPS+Hm and CCK-8+LPS group were higher than those in LPS group. However, the degree of lung injury, PMN number and MDA content were higher, CO content were lower in LPS+ZnPP and CCK-8+LPS+ZnPP group than those in LPS and CCK-8+LPS group, respectively. CONCLUSION: CCK-8 attenuates the LPS-induced acute lunginjury by means of anti-oxidation and inhibition of PMN aggregation, which are both mediated by CO.  相似文献   

10.
AIM: To investigate the effect of hydrogen sulfide (H2S) on high glucose （HG）-induced injury of the mouse podocyte cell line MPC5. METHODS: The cultured MPC5 cells were randomly divided into 4 groups: HG group, normal glucose (NG) group, NG+DL-propargylglycine (PPG) group, and HG+NaHS group. After treated for a certain time, the cells were collected for further detection. The expression of zonula occludens-2 (ZO-2), nephrin, β-catenin and cystathionine γ-lyase (CSE) was determined by Western blotting. RESULTS: High glucose significantly reduced the expression of nephrin, ZO-2 and CSE (P<0.05), while the level of β-catenin was elevated obviously (P<0.05), all in a time-dependent manner. NG+PPG inhibited the levels of ZO-2 and nephrin significantly (P<0.05), and increased the level of β-catenin (P<0.05), all in a PPG concentration-dependent manner. HG+NaHS induced a more significant increase in the levels of ZO-2 and nephrin as compared with HG group (P<0.01), whereas a severe reduction of β-catenin in HG+NaHS group was observed as compared with HG group. Compared with NG group, the expression of ZO-2 and nephrin was decreased obviously, and the level of β-catenin was increased in HG+NaHS group. CONCLUSION: Down-regulation of CSE contributes to hyperglycemia-induced podocyte injury. Exogenous H2S protects against hyperglycemia-induced podocyte injury, possibly through up-regulation of ZO-2 and subsequent suppression of Wnt/β-catenin pathway.  相似文献   

11.
AIM: To investigate the changes of endogenous cystathionine-γ-lyase/hydrogen sulfide pathway on hypoxia/reoxygenation injury in vivo and to explore the relationship between this pathway and hypoxia/reoxygenation injury. METHODS: Primary myocardial cell culture in vivo came from Wistar baby rats born less than 48 h. The cells were under the conditions of hypoxia (2% O2, 5% CO2) for 3 h and reoxygenation (21% O2, 5% CO2) for 2 h to induce hypoxia/reoxygenation injury. MTT was used to detect the cell survival in every group. The activities of lactate dehydrogenase (LDH) in culture medium, malondialdehyde (MDA) and superoxide dismutase (SOD) in myocardial cells were measured with colorimetry method. RT-PCR method was used to test CSE mRNA expression in myocardial cells. RESULTS: Compared to IR group, the cells in NaHS+IR and IR+NaHS groups had a higher survival rate, lower LDH concentration in culture medium, higher SOD activity and lower MDA in myocardial cells. At the same time, the results of RT-PCR displayed that CSE mRNA were down-regulated in myocardial cells after hypoxia/reoxygenation injury, and if CSE inhibitor PPG was added into the culture medium before hypoxia, no protective effects were detected. CONCLUSION: NaHS might protect the myocardial cells from hypoxia/reoxygenation injury through decreasing oxygen free radical production and stabilizing the cell membrane.  相似文献   

12.
AIM: To explore the effects of exogenously applied hydrogen sulfide (H2S)on expression of urotensin II (U-II)in rats with ovalbumin-induced acute asthma. METHODS: Twenty-four male SD rats were randomly divided into control group, asthma group and NaHS treatment group (all n=8). At the 28th day after ovalbumin sensitization, the pulmonary function was measured. The pathological changes in the lung tissues were observed. The contents of U-II in plasma, lung tissues and bronchoalveolar lavage fluid (BALF)was also detected.RESULTS: The peak expiratory flow (PEF) was(6.5±0.1)L/s,(2.9±0.7)L/s and(5.7±0.5)L/s in control group, asthma group and NaHS treatment group, respectively. No statistical difference of the plasma U-II levels was observed among the three groups. In asthma group, the content of U-II in lung tissues was(43.8±2.0)ng/L and that in BALF was(58.0±12.3)ng/L, both of which were significantly higher than those in control group . In NaHS treatment group, the content of U-II in lung tissues was(14.0±1.9)ng/L and that in BALF was(20.2±6.7)ng/L, both of which were significantly lower than those in asthma grou p (F=337.68 and F=38.433, respectiuely, both P<0.01). The pathological score of the lung tissues in asthma group was 3(2-4), significantly higher than that in control group and NaHS treatment group . The positive correlations between the contents of U-II in lung tissues or BALF and the pathological scores were observed (r=0.746,r=0.714, respectively, both P<0.01). Significantly negative correlations between the contents of U-II in lung tissues or BALF and PEF were also found (r=-0.911 and r=-0.767, respectively, both P<0.01).CONCLUSION: U-II, a mediator acting via the way of paracrine or autocrine, may play a role in the pathogenesis of asthma in this animal model. The exogenous application of H2S may play a regulatory role in asthma through inhibiting U-II to attenuate the inflammatory responses in asthma and exert protective effect on the pulmonary functions.  相似文献   

13.
AIM: To investigate the effect of hydrogen sulfide on neuron apoptosis through PI3-K/Akt/P70S6K cell-survival signal transduction pathways after neuron anoxia-reoxygenation.METHODS: Newborn (24-48 h) Wistar rats were decapitated.The hippocampus tissue was dissected and cells were suspended.Cells were plated at 1.0×108 cells/L on poly-dlysine-treated 96-well (100 μL/well) plates and 6-well (2 mL/well) plates.Cells were used after 7 days.For anoxia-reoxygenation (oxygen glucose deprivation,OGD) experiments,cells were washed three times in a glucose-free balanced salt solution (BSS).They were then placed in deoxygenated glucose-free medium and cultured under 95% N2,5% CO2 in an anaerobic chamber equilibrated to 37 ℃ and 100% humidity for 45 min.OGD was terminated by replacement of stored medium and by returning the cultures to a standard incubator maintained at 37 ℃ in 95% air,5% CO2.In experimental group,cells were respectively carried out OGD,OGD+150 μmol/L NaHS,OGD+150 μmol/L NaHS+10 μmol/L triciribin,OGD+150 μmol/L NaHS+10 nmol/L rapamycin and OGD+150 μmol/L NaHS+10 μmol/L triciribin+10 nmol/L rapamycin.Control cells were cultured normally.24 h later,neuron viability and apoptosis were measured.The level of cAMP and protein expression of PI3-K,Akt and P70S6K were detected.RESULTS: NaHS enhanced concentration of cAMP and expression of PI3-K,Akt and P70S6K.Meanwhile,increased neuron viability and decreased neuron apoptosis (P<0.01 vs group C or group I/R) were observed.Triciribin inhibited Akt and P70S6K,as well as increased neuron apoptosis and decreased neuron viability (P<0.05,P<0.01 vs group NaHS).Rapamycin inhibited P70S6K,as well as increased neuron apoptosis and decreased neuron viability (P<0.05,P<0.01 vs group NaHS).CONCLUSION: H2S inhibits hippocampus neuron apoptosis and protects neuron from anoxia-reoxygenation injury through cAMP-mediated PI3-K/Akt/P70S6K kinase cell-survival signaling pathways.  相似文献   

14.
AIM: To study the protective effect of heat shock factor1 (HSF1) on the mice with lipopolysaccharide (LPS)-induced acute lung injury (ALI), and to screen the relevant differentially-expressed genes. METHODS: ALI mouse model was established by LPS intracheal instillation. The macroscopic and pathological changes of the lung tissue were observed, and the concentrations of total protein, TNF-α, IL-β, IL-6 and VEGF in the bronchoalveolar lavage fluid (BALF) were analyzed. Differentially-expressed genes in the lung tissues of HSF1+/+ mice and HSF1-/- mice with ALI induced by LPS were screened by gene chips. The key gene was verified by real-time qPCR. RESULTS: The macroscopic and pathological changes of the lung injury in HSF1-/-+LPS mice were more serious than those in HSF1+/++LPS mice. The concentrations of total protein, VEGF, TNF-α, IL-1β and IL-6 in the BALF of HSF1-/-+LPS mice were significantly higher than those of HSF1+/++LPS mice (P<0.05). Compared with the HSF1+/+ mice, a total of 918 differentially-expressed genes were indentified in the HSF1-/- mice, among which the expression levels of 65 genes had obvious diffe-rence, with 28 genes up-regulated, including Atg7, ccr1, cxcr2, Tbl1xr1, Mmp9, Pparg, Plcb2, Arrb2, Cntn1, Col4a6, etc, and 37 genes down-regulated, including Fgfr1, Fgfr2, Map4k4, Ddx58, Tfg, Stat3, Smad4, Lamc1, Sdc3, etc. The results of real-time qPCR showed that the mRNA level of CXCR2 in HSF1-/-+ LPS mice was significantly higher than that in HSF1+/++ LPS mice, which was consistent with the results of gene chips. CONCLUSION: HSF1 has protective effect on the mice with LPS-induced ALI. CXCR2 may be involved in the protective effect of HSF1 on this process.  相似文献   

15.
AIM: To observe the changes of endogenous hydrogen sulfide/cystathionine-γ-lyase (H2S/CSE) system while acute lung injury induced by LPS in rats. METHODS: Eighty rats were randomly divided into six groups (n=8): Ⅰ, control group;Ⅱ, LPS 1 h group; Ⅲ, LPS 3 h group; Ⅳ, LPS 6 h group; Ⅴ, LPS 9 h group; Ⅵ, LPS 12 h group. The ALI model of rats was prepared with LPS. The rats were respectively killed at 1, 3, 6, 9 or 12 h after administration of LPS. The morphological changes of lung tissues were observed by light and electron microscope. The lung coefficient and the wet-to-dry weight ratio were measured. The contents of IL-1β and IL-10 in serum, the H2S level in plasma and the CSE activity in lung tissue were respectively detected. RESULTS: ⑴ In LPS 1 h group, the morphology, the lung coefficient, the wet-to-dry weight ratio, the H2S level and the CSE activity showed no changes compared with the control group. The contents of IL-1β and IL-10 were increased compared with the control group (IL-1β, P<0.05;IL-10, P<0.01). ⑵ In LPS 3 h, 6 h, 9 h and 12 h groups, compared with the control group, the lung tissues were significantly damaged, the lung coefficient and the wet-to-dry weight ratio were significantly increased respectively (LPS 3 h, P<0.05; LPS 6 h, 9 h, 12 h, P<0.01). The contents of IL-1β and IL-10 in serum were markedly increased (P<0.01). The H2S level in plasma and the CSE activity in lung tissue were significantly decreased (P<0.01).CONCLUSION: The changes of inflammatory cytokines may be the pathological foundation of the ALI induced by LPS and the endogenous hydrogen sulfide/cystathionine-γ-lyase system is possibly involved in the formation of the ALI.  相似文献   

16.
AIM:To approach the relationship between the expression of intercellular adhesion (ICAM-1 mRNA) and acute lung injury (ALI) as well as the mechanisms of rhubarb in the prevention and treatment of the lung injury. METHODS:ALI animal model was performed by Lipopolysaccharide (LPS). The rats were divided into 4 groups: LPS group, control group, rhubarb+LPS group and dexamethasone+LPS group. Histopathological examination and biological markers were measured for the lung specimens. Molecular hybridization method was used to determine the expression of ICAM-1 mRNA. RESULTS:The ICAM-1 mRNA expression in the lung tissues of LPS group significantly increased compared with control group (P＜0.01), rhubarb and dexamethasone had the action of decreasing the ICAM-1 mRNA expression (P＜0.05, P＜0.01); pathologic changes and the biological markers of ALI significantly decreased or ameliorated. CONCLUSION:The increase in the expression of ICAM-1 mRNA in the lung tissues of ALI is involved in the formation of ALI. Rhubarb and dexamethasone can ameliorate the lung damage, mechanism of which may be related to the inhibition of ICAM-1 mRNA expression.  相似文献   

17.
AIM: To study the production of intercellular adhesion molecule-1(ICAM-1), E-selectin and P-selectin in serum, lung tissues and bronchoalveolar lavage fluid(BALF)of acute lung injury(ALI) model and to observe the effects of ambroxol combined with low-dose heparin on the changes of the 3 factors above.METHODS: Twenty-four healthy rabbits were randomly divided into 3 groups: normal saline control group (NC), oleic acid injury group (OA), ambroxol+ heparin treatment group (AH). The rabbit ALI model was induced by oleic acid injection through auricular vein. Partial pressure of O2 in artery(PaO2) was analyzed.The concentrations of ICAM-1 and E-selectin were detected by ELISA.The apoptosis index(AI) was measured by TUNEL method.The expression of P-selectin was determined by immunohistochemical method.The ultrastructural changes of the lung tissues were observed under electron microscope, and the lung wet/dry ratio(W/D) was calculated.RESULTS: PaO2 in AH group and OA group was significantly lower (P<0.01) than that in NC group, and PaO2 in AH group was significantly higher than that in OA group (P<0.01). The concentrations of ICAM-1 and E-selectin in serum, lung tissues and BALF, and AI and W/D in lung tissues in AH group were higher (P<0.05 or P<0.01) than those in NC group, and was lower than those in OA group (P<0.05 or P<0.01). In NC group, no significant change of the above parameters at all time points was observed (P>0.05). In OA group, PaO2 was significantly decreased (P<0.01) with the pathological process developed, and the concentrations of ICAM-1 and E-selectin were significantly increased. In AH group, PaO2 was decreased (P<0.05),and the concentrations of ICAM-1 and E-selectin were increased with the process of ALI developed. The P-selectin expression in lung tissues of OA group was distributed mainly in inflammatory cells, capillary endothelial cells and plasma. From low to high levels, the order was NC group < AH group < OA group in the expression of P-selectin. The most obvious apoptosis was observed in OA group. No apoptosis or occasional positive cells were found in NC group. The apoptotic rate in AH group was significantly reduced compared with that in OA group.CONCLUSION: In ALI induced by OA, ICAM-1, E-selectin and P-selectin are significantly increased and are involved in the occurrence and development of ALI. Ambroxol combined with low-dose heparin reduces the levels of ICAM-1, E-selectin and P-selectin, the pulmonary edema and the lung injury, improves pulmonary functions, and plays an important role in the prevention and treatment of acute lung injury.  相似文献   

18.
AIM: To observe the chronological changes of pulmonary apoptosis and the expression of iNOS mRNA,nNOS mRNA and eNOS mRNA in lipopolysaccharide (LPS)-induced acute lung injury (ALI) and to investigate the mechanisms of ALI.METHODS: Rats were randomly divided into 2 groups: control group and LPS treated group.The rats were injected with either saline or LPS and killed at 1,3,6,9 and 12 h after LPS injection.The expressions of iNOS mRNA,nNOS mRNA and eNOS mRNA in the lung tissue were respectively measured with RT-PCR methods.Apoptosis and expressions of Bcl-2 and Bax were respectively determined by flow cytometry (FCM) and immunohistochemistry (IHC).The pathological changes of lung tissue were observed under light and electron microscope.RESULTS: Compared with that in control group,the expression of iNOS mRNA was significantly increased at 3,6,9 and 12 h after administration of LPS (P<0.05).The eNOS mRNA was significantly decreased at 3,6,9 and 12 h after administration of LPS (P<0.05).The nNOS mRNA had no significant change during the 12 h in LPS group.Degree of ALI was gradually worsened after administration of LPS.Apoptosis of pulmonary cells was significantly increased,and reached the top level at 9 h after administration of LPS (P<0.01).The expression of Bcl-2 was markedly decreased and the expression of Bax was significantly enhanced in alveolar and airway epithelial cells in LPS treated group.CONCLUSION: The expressions of iNOS mRNA,eNOS mRNA and nNOS mRNA are not identical in LPS-induced acute lung injury.NOS regulates the apoptosis of pulmonary cells through affecting the balance of Bcl-2 and Bax.  相似文献   

19.
AIM: To study the signal pathway involved in up-regulation of LPS-induced HO-1 expression by CCK-8. METHODS: Forty-two SD rats were divided into 7 groups (six rats each) randomly as follows: control group, LPS group, LPS+SP600125 (JNK-specific inhibitor) group, CCK-8+LPS group, CCK-8+LPS+SP600125 group, CCK-8 group and CCK-8 +SP600125 group. Lungs from the rats in these 7 groups were excised 6 h after the agents were administered. HO-1 mRNA expression was examined by RT-PCR. The protein expression of HO-1 was detected by Western blotting and immunofluorescence flow cytometry (FCM). RESULTS: There were significant positive expression of HO-1 mRNA in LPS group compared to control group. CCK-8 enhanced LPS-induced HO-1 mRNA expression and CCK-8 alone induced HO-1 mRNA expression as well. The mRNA expressions of HO-1 in LPS group, CCK-8+LPS group and CCK-8 group were 3.01 (P<0.01), 5.88 (P<0.01) and 3.45 (P<0.01) times as many as that in control group, respectively. SP600125 inhibited the mRNA expression of HO-1 induced by CCK-8 and (or) LPS. The change of HO-1 protein expression was in accordance with that of HO-1 mRNA expression by Western blotting and immunofluorescence FCM. CONCLUSION: These results suggest that JNK/c-Jun signal pathway plays an important role in the up-regulation of LPS-induced HO-1 expression by CCK-8.  相似文献   

20.
AIM: To determine the differences in phosphoproteome between LPS stimulated THP-1 cells with and without previous oxidative stress for screening of more potential regulators.METHODS: Differentiation of THP-1 cells into macrophages was induced by treatment with 100 μg/L PMA for 36 h. Differentiated cells were rested for additional 36 h without PMA treatment, then treated with 100 μmol/L H2O2 or medium for 1 h followed by LPS or medium treatment for 30 min. After desalted, phosphoproteins were enriched by phosphoprotein metal affinity column, and were run on 2-D electrophoresis, then the spots were analyzed to show the difference between LPS group (cells treated with LPS alone) and H2O2+LPS group (LPS stimulated cells also pretreated with H2O2). Finally, some of these spots were identified by MS and subsequent bioinformatic analysis was also conducted. RESULTS: Compared to LPS group, 29 reproducibly changed spots on the 2-D map in H2O2+LPS group were visualized and selected for MS analysis. Among these, 12 down-regulated spots (include those disappeared), 17 up-regulated spots (include those newly emerged) were selected. Up to now, 5 of these were identified, which were shown to be involved in various cellular processes such as proteolysis, signal transduction and protein folding. Among these, proteasome beta-4 subunit, which was dramatically down-regulated in H2O2+LPS group, was a major component of the proteasome complex and might participate in LPS signalling through various ways.CONCLUSION: With comparative phosphoprotein-affinity profiling, the interference brought by highly abundant house-keeping proteins is minimized, rendering us to detect less abundant signalling molecules. Aforementioned 5 proteins, especially proteasome beta-4 subunit, might be involved in LPS pathway reprogrammed by oxidative stress.  相似文献   

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