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1.
AIM:To observe the alteration of urotensin II (UII) receptors and contractile response to UII in rat aorta after balloon angioplasty injury. METHODS: The plasma membrane isolated from balloon injured aorta was used to study the binding of 125-UII to the membrane and the contractile potency of UII on rat aorta was assayed. RESULTS: In contrast to the normal aorta, the contractile potency to UII enhanced in balloon injury artery and the calculated maximal number of specific binding sites (Bmax) was increased about 44% and 36% respectively in rat artery after balloon injury 3 and 21 days (P＜0.01). CONCLUSION: The density of UII receptors and the contractile response to UII had changed after balloon angioplasty injury. It was proposed that UII might play an important role in the intervention of restenosis after angioplasty.  相似文献   

2.
AIM: To study the effects of angiotensin Ⅱ type 2 receptor (AT2R) gene transfer on neointimal hyperplasia in rat carotid arteries after balloon angioplasty. METHODS:AT2R gene was transfected into rat carotid arteries with pAdCMV/AT2R after the establishment of rat carotid balloon injury restenosis model. The arteries were harvested at 7 days, 14 days and 21 days after gene transfer. The expression of AT2R, AT1R, PCNA in arteries and morphology analysis were evaluated by RT-PCR, immunohistochemistry and HE staining. The expressions of AT2R and PCNA were measured by double immunofluorescence staining and confocal microscope. RESULTS:pAdCMV/AT2R delivered into injured rat carotid arteries significantly up-regulated the levels of AT2R mRNA and protein in neointima from day 7 to day 21, but the levels of AT1R was not significantly different (P>0.05). pAdCMV/AT2R transfection significantly decreased the expression of PCNA in neointima at day 14 ［(27.29±5.81)% vs ( 72.25±4.47)%, (68.43±9.12)%，P<0.01］. At day 21, compared with no transfection group and pAd-GFP transfection group, pAdCMV/AT2R transfection reduced I/M (intimal/medial area) ratio significantly (0.78±0.06 vs 1.44±0.22, 1.36±0.21， respectively, P<0.01). No significant difference between pAd-GFP group and no transfection group was observed. CONCLUSION: Gene transfer of AT2R from lumen may effectively inhibit VSMC proliferation and neointimal hyperplasia in the rat carotid arteries after balloon angioplasty. The cross-talk between AT1R and AT2R may operate via signaling pathway, but not via counteraction of receptor expression.  相似文献   

3.
AIM:To investigate the effect of L-arginine (L-Arg) on intimal proliferation and expression of related cell cycle regulatory factors after vascular injury in rats. METHODS:Rats were divided into three groups :sham operation group, balloon injury group(this group included balloon 48 h,7 d and 14 d subgroup) and balloon+L-Arg group. Neointima area were calculated morphologiocally. The expression of cyclin dependent kinase-2(CDK2),cyclin E and proliferation cell nuclear antigen (PCNA) were measured by means of immunohistochemical technique and computer image analyzer. RESULTS:After vascular balloon injury, the level of plasma NO decreased, CDK2、cyclin E and PCNA expressed in the media at 48 h and in the neointima at 7 d and 14 d but with low and undetected expression in the media, the expression of CDK2, cyclin E and PCNA increased with the intima thickening. Compared with balloon 14 d group, the plasma NO level increased (P＜0.01), the neointima area reduced by 59.1%(P＜0.01) and the positive expression indexes of CDK2, cyclin E and PCNA decreased by 36.1%, 46.3% and 76.2% respectively in balloon+L-Arg group (P all＜0.01). CONCLUSION:L-Arg can effectively repress intima proliferation after vascular injury, which may be associated with its inhibiting the proliferation of vascular smooth muscle cell through downregulating the excessive expression of CDK2, cyclin E and PCNA.  相似文献   

4.
AIM: To observe the level of metallothionein (MT) in liver, aorta and plasma of rabbit with atherosclerosis (AS) in order to recognize the alteration of oxidative defense system in body when AS occurred.METHODS:Preparation of AS model of rabbit induced by having high-fat diet for eight weeks; the levels of MT and malondialdehyde (MDA) were measured in the tissues of liver and aorta and plasma of rabbit.RESULTS:The MT levels in liver tissues and plasma in atherosclerotic group increased 318%(P＜0.01) and 62% (P＜0.01), compared with control group, but its level in aortic tissue in atherosclerotic group decreased 33% (P＜0.01). The MDA levels in liver, aortic and plasma in atherosclerotic group increased 95%(P＜0.01), 76%(P＜0.01) and 42%(P＜0.01), respectively, compared with control group. The changes of contents of MT in liver and plasma have relation with level of MDA in liver tissues and plasma.CONCLUSION:The alteration of MT in liver tissues and plasma in atherosclerotic rabbits may be related to lipid hyperoxidative injury.  相似文献   

5.
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6.
AIM:To investigate the effect of endothelin (ET), angiotensin II (AngII) and homocysteine (Hcy) on C-type natriuretic peptide (CNP) synthesis and release. METHODS: Human endothelial cell was cultured; CNP was measured by radioimmunoassay method. RESULTS: ET and AngII could augment CNP synthesis in human endothelial cells. Compared with control group, 10-9,10-8,10-7 mol/L ET and Ang II increased CNP content of endothelial cells by 1%(P＞0.05), 49%(P＜0.05),117%(P＜0.01) and 137% (P＜0.01),165%(P＜0.01),201%(P＜0.01),respectively. A great dose of ET and Ang II also stimulated CNP release from cultured human endothelial cells. Hcy had no effect on CNP synthesis, but 10-9,10-8,10-7 mol/L Hcy enhanced CNP release from cultured human endothelial cells by 17%(P＞0.05),84%(P＜0.01) and 555%(P＜0.01), respectively. CONCLUSION: ET, AngII and Hcy might be involved in the synthesis and release of human endothelial cell CNP.Fig 1 Time-course of CNP syntheis and release in cultured human endothelial cell ( ±s,n=6)  相似文献   

7.
AIM: To explore the possible effect of UII in the process of remodeling after vascular injury. METHODS: The rat model of balloon injury in thoracic aorta was established. Male rats were randomized to 4 groups (n=5), including sham injury group, injury group, UII group (UII pumped into the rats after thoracic aorta balloon injury at 1.0 nmol·kg-1·h-1) and urantide group (urantide pumped into the rats after thoracic aorta balloon injury at 10 nmol·kg-1·h-1). At 21 days, the thoracic aortas were taken out to measure the changes of pathology, the expression of UII, the proliferation of VSMC and the expression of collagen. RESULTS: (1) At the 21 days after operations, the systolic blood pressure was higher in UII group than that in injury group ［(140.0±10.0) mmHg vs (132.0±3.4) mmHg, P>0.05］. The systolic blood pressure was also obviously higher than that in urantide group ［(140±10.0) mmHg vs (128.0±2.4) mmHg, P<0.05］. (2) Urotensin Ⅱ was expressed strongly in the injured area after thoracic aorta injury. (3) In contrast to injury group, the intimal thicken in urotensin Ⅱ group enhanced, the decrease in lumen area was marked (0.13±0.05 vs 0.07±0.02, P<0.05), the cell proliferation index was markedly increased (0.74±0.16 vs 0.40±0.11, P<0.01), and the expression of collagen was also markedly increased (counted as IOD, 318±127 vs 78±26, P<0.01). (4) In contrast to injury group, the decrease in lumen area was not abolished (0.09±0.03 vs 0.07±0.02, P>0.05) after chronic infusion of urotensin Ⅱ receptor antagonist urantide, the cell proliferation index was markedly increased (0.73±0.15 vs 0.40±0.11, P<0.01) and the expression of collagen was not statistically increased (counted as IOD, 200±79 vs 78±26, P>0.05). CONCLUSION: Urotensin Ⅱ expresses strongly in the myointimal cells after thoracic aorta injury in rat. The extra UII enhances the proliferation of VSMC and expression of collagen in the myointimal, increases the stenosis of injured vasculature, indicating that UII might take part in the process of repairing after vessel injury.  相似文献   

8.
AIM:To study the effect of mobilization of stem cells by exogenous recombinant human granulocyte-colony stimulating factor (rhG-CSF) on the repairing process of reendothelialization and neointima hyperplasy on ballon injured rat carotid arteries.METHODS:Male Wistar rats were randomly divided into rhG-CSF group and NS+injury group.The animals were injected daily with 30 μg/kg rhG-CSF or 0.9% NaCl for 7 days,then underwent balloon angioplasty of the common carotid arteries which were harvested and processed for scanning electron microscopy (SEM),Evans blue staining,morphometric analysis of endothelialization and neointimal formation at 1 h,3 d,5 d,7 d,14 d after injury.Immunohistochemistry for proliferation cell nuclear antigen (PCNA) and RT-PCR for eNOS mRNA were also conducted for evaluating the proliferation of cells of the vessel wall and the possible mechanism of the repairing.RESULTS:SEM and Evan’s blue staining showed increased reendothelialization of the denuded vessels in rhG-CSF-treated animals compared with that NS+injury animals ［(60.6±7.3)% vs (41.6±3.3)%，P<0.01］.Neointima thickness was reduced by 37.3% in rhG-CSF group compared with NS+injury group 2 weeks after injury.Immunohistochemical staining for PCNA positive cells was less in rhG-CSF group compared with that in NS+injury group (42.6% vs 72.8%,P<0.01).CONCLUSION:rhG-CSF has beneficial effects on the reendothelialization and neointima thickness of the ballon-injured arteries.Mobilization of EPCs by exogenous granulocyte colony stimulating factor may be a potential therapeutic strategy for prevention of restenosis after percutenous coronary artery intervention.  相似文献   

9.
AIM:To observe the changes in neuropeptide Y(NPY) and the effect of Fu-Sheng powder(FSP) on NPY in the rat brain in a steady cerebral ischemia and reperfusion(I/R) model. METHODS: The models of rat brain injury were established by repeated cerebral I/R in rats with hyperlipidemia. Radioimmunoassay was performed to determine the level of NPY, while NPY mRNA expression was observed by in situ hybridization. RESULTS: After 1 day of I/R, compared with control group, the content of NPY in the model animals were significantly increased by 51.86% (P＜0.01) and lasting 7 days after I/R, and the expression of NPY mRNA was greatly increased. FSP treatment decreased the contents of NPY (P＜0.05,P＜0.01) and its mRNA expression. CONCLUTION: There were obvious imbalances of NPY in the rat brain after cerebral I/R and the FSP might antagonize ischemia injury of brain through modulating NPY, which may be one of the mechanisms underlying FSP treatment for cerebral vascular diseases.  相似文献   

10.
AIM:To investigate alteration of functional receptors for urotensin II in pressure overload-induced cardiac hypertrophy of rats. METHODS: In the rat cardiac hypertrophy model produced by constriction of the abdominal aorta, urotensin II binding sites in myocardial sarcolemma were determined with radioligand assay first day (early group) and 30th day (late group) after operation. RESULTS:Compared with control and sham group, in the early group,the blood pressure increased 54% and 43% respectively(P＜0.01),and heart/body weight ratio unchanged(P＞0.05),UII receptors were up-regulated by 184% and 159%(P＜0.01)respectively, While the affinity to UII was decreased (Kd increased 224% and 206 respectively,P＜0.01).In the late group, the blood pressure increased 85% and 67% (P＜0.01), and heart/body weight ratio increased 18% and 22% (P＜0.05) respectively,than that of control and sham group. UII receptors were down-regulated by 35% and 41%(P＜0.05) respectively while the affinity to UII was increased (Kd decreased 30% and 33% respectively, P＜0.05). CONCLUSION: The biphasic changes of UII receptor in myocardial sarcolemma induced by pressure-overload were observed,increasing in early stage, while decreasing in late stage, and these changes were involved in the development of cardiac hypertrophy.  相似文献   

11.
AIM: To investigate the mechanism of vascular smooth muscle cells (VSMC) apoptosis after balloon injury. METHODS: VSMCs apoptosis, Bax protein and Bcl-2 protein was measured by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) and immunohistochemical technique after balloon injury. RESULTS:VSMCs apoptosis occurred in vascular media at 3 days after balloon injury and reached a peak in media and intima where apoptosis was mainly present at 7 days, then decreased. At 28 days after balloon injury, only a few apoptosis cells were in intima. Irbesartan significantly increased VSMCs apoptosis (P＜0.01). Expressions of Bax and Bcl-2 were significantly higher in vascular media at 3 days after balloon injury than sham(P＜0.01). At 7 days, Bax expression reached a peak which was three times as that of sham, and then decreased. After balloon injury, Bcl-2 expression was generally increased and reached its peak at 28 days. The ratio of Bax to Bcl-2 (Bax/Bcl-2) also reached its peak at 7 days and was decreased under basal level at 28 days. Irbesartan increased Bax and the ratio of Bax to Bcl-2, while decreased Bcl-2. CONCLUSION: Bcl-2 and Bax contribute to the regulation of VSMC apoptosis after balloon injury.  相似文献   

12.
AIM: To investigate the effect of basic fibroblast growth factor (bFGF) on C-type natriuretic peptide (CNP) production, release and mRNA expression. METHODS: Human endothelial cell cultured;CNP was mea sured by radioimmunoassay method;CNP mRNA expression was determined by RT-PCR technique.RESULTS: bFGF could augment CNP synthesis in human endothelial cells. Compared with control group,25 ng, 50 ng, 100 ng bFGF increased CNP contents in endothelial cells by 88% (P＜0.05), 95% (P＜0.05), 187% (P＜0.01), respectively.100 ng bFGF also stimulated CNP release from cultured human endothelial cell. In addition, 25 ng, 50 ng and 100 ng bFGF stimulated CNP mRNA expression of cultured human endothelial cells in a dose-dependent manner. CONCLUSION: bFGF might regulate CNP synthesis,release and mRNA expression in cultured umbilical human endothelial cells.  相似文献   

13.
AIM: To determine the effects of recombinant human interleukin-10(rhIL-10) on proliferation of vascular smooth muscle cells(VSMC) by TNF-α and PDGF-BB and neointimal hyperplasia after rat carotid arterial injury.METHODS: Rat aortic VSMC was cultured and treated with rhIL-10 with or without tumor necrosis factor-α(TNF-α) and platelet-derived growth factor-BB (PDGF-BB), respectively.Proliferation of VSMC was quantified by colormetric assay.Cell cycle analysis was performed by flow cytomertry.SD rats were treated with recombinant human IL-10(rhIL-10) for 3 days after carotid arteries injury.Neointima to media area ratio at the site of arterial injury was measured at 28 days after balloon injury.RESULTS: Compared to control,both TNF-α and PDGF-BB stimulated VSMC proliferation. rhIL-10 alone had no effect on VSMC growth.With TNF-α or PDGF-BB stimulation,rhIL-10,at dose as low as 10 μg/L,inhibited VSMC growth( P <0.05) for both cases.Cell number in G 0/G 1 phase of PDGF-BB and rhIL-10 co-treatment group was higher than those of PDGF-BB treatment alone( P <0.01) by flow cytometry analysis.The same results were observed in TNF-α and rhIL-10 co-treatment group( P <0.01).Compared with the arterial injury group,neotima/media area ratio of recombinant human IL-10 group was reduced at 45%( P <0.01).CONCLUSIONS: The anti-inflammatory cytokine rhIL-10 inhibits TNF-α and PDGF-BB-induced VSMC proliferation,respectively.These results suggest the possibility that recombinant human IL-10 as a potential therapeutic approach prevents neointimal hyperplasia.  相似文献   

14.
AIM: To observe the effect of cyclosporine A on intima hyperplasia of rat abdominal aortas injured by balloon.METHODS: Thirty-six healthy adult male SD rats were randomly divided into 3 groups: sham group (n=12), balloon-injured group (n=12) and cyclosporine A treatment group (n=12).From the 3rd day before injury to the 30th day after injury, the rats in cyclosporine A treatment group were treated with cyclosporine A at a dose of 12.5 mg/kg everyday, while the rats in sham group and balloon-injured group were fed with the same volume of water.On the 30th day after injury, the specimens were obtained from the rats.HE staining and immunohistochemistry were used to measure the expression level of calcineurin (CaN) in arterial wall.Pathological changes of the arterial wall were observed under light microscope.The expression of CaN and nuclear factor 3 of activated T-cells(NFATc3) in the abdominal aortas was detected by the technique of real-time PCR.RESULTS: Intimal hyperplasia was observed in balloon-injured rats.The neointima was not uniform in thickness on the 30th day.The thickness of the intimal layers and the ratio of the intimal to the medial layers in cyclosporine A group were obviously lower than those in balloon group(P<0.05).Immunohistochemistry revealed that calcineurin expression increased after balloon injury, but the expression of calcineurin in cyclosporine A group was obviously decreased as compared with balloon group (P<0.05).The results of real-time PCR showed that the mRNA expression of calcineurin and NFATc3 in cyclosporine A group was significantly lower than that in balloon-injured group (P<0.05).CONCLUSION: Cyclosporine A attenuates restenosis by suppressing the CaN-NFATc signaling pathway.  相似文献   

15.
AIM:To observe the change of nitric oxide (NO) generation system in the vascular adventitia, media and intima in septic shock rats.METHODS:The septic shock model was made in rats by caecal ligation and puncture. The intima, media and adventitia of the rat aorta were separated. NO production (NO2-), nitric oxide synthase(NOS) activity and L-arginine (L-Arg) transport were measured, separately. Inducible NOS (iNOS) distribution was detected by immunohistochemistry.RESULTS:Both in early and late stage of septic shock, NO2- from the intima was decreased by 66.1% and 78.9%(P<0.01), while NO2- from the media was increased by 1.1 and 2.2 folds(P＜0.01), and the adventitia 9.6 and 18.6-fold (P＜0.01), as compared with the sham group, respectively. The changes of NOS activity and the L-arginine transport in the intima, the media layer and the adventitia of the aorta in the septic shock rat paralleled with that of NO2- in these tissues. The results of iNOS immunohistochemistry showed that there were obviously positive staining in the media layer and adventitia, especially the adventitia of the rat aortas in septic shock, as compared with that in the sham control.CONCLUSIONS:During septic shock, NO production in the aortic intima was progressively suppressed. However, it was progressively increased in the aortic medial layer and adventitia, especially the adventitia with shock processes. These changes result from different changes of L-arginine transport, NOS activity and its expression in three layers of the aorta from the septic shock rat.  相似文献   

16.
AIM: To investigate the effects of testosterone on endothelial function and intimal proliferation after balloon injury in male rabbit abdominal aorta. METHODS: 24 male New Zealand white rabbits were divided randomly into three groups: control group (n=8, sham castration), hypotestosteronemia group (n=8,castration) and testosterone replacement group (n=8,castration +testosterone undecanoate intramuscular injection,14mg/kg). Abdominal aorta was injured with 3 mm PTCA balloon after testosterone undecanoate had been injected for three days. Two weeks later, blood samples were obtained for detection of plasma testosterone, lipids, metabolic product of nitric oxide (NO2-／NO3-), superoxide dismutase(SOD) and malondialdehyde (MDA),and all the abdominal aorta were excised to be analyzed by computer. RESULTS: The intimal area of hypotestosteronemia group were significantly larger than that of other two groups(P＜0.01). plasma NO2-／NO3- and SOD levels were significantly decreased, while the total cholesterol(TC),triglycerides(TG), low density lipoprotein(LDL) and plasma MDA were significantly increased. No difference was observed between control group and testosterone replacement group in all parameters. CONCLUSION: Testosterone, at physiological level,had the effects of inhibiting the intimal proliferation and of protecting the endothelial function after balloon injury in male rabbit abdominal aorta.  相似文献   

17.
AIM: To investigate the effect of endogenous and exogenous carbon monoxide on the proliferation of pulmonary artery smooth muscle cells under anoxic condition. METHODS: Primary culture of rat PASMCs were passed every 3 days, the 3-5 passages were used. PASMCs were divided into 5 groups, cultured under normoxia and hypoxia and treated with HO inducer hemin, CO scavenger bovine hemoglobin (Hb) and exogenous carbon monoxide (CO), respectively. After 48 hours incubation under the conditions mentioned above, the following assay were carried out: 1) the MTT colorimetric assay and immunocytochemical staining were used to study the energy metabolism and the expression of proliferating cell nuclear antigen (PCNA) in PASMCs. 2) flow cytometry was used to analyze the cell cycle of PASMCs. RESULTS: In comparison with the control group, the value of MTT colorimetric assay was higher, the immunocytochemical staining of PCNA was stronger and the percentages of PASMCs in S and G2M phases in the anoxia group were higher (P＜0.01). After treatment with hemin and CO, the above indexes were decreased (P＜0.01 or P＜0.05). But treatment with Hb made the above indexes increased (P＜0.01 or P＜0.05). CONCLUSION: The endogenous CO suppress the proliferation of PASMC in an autocrine way. Both the induction of endogenous CO by hemin and the treatment with exogenous CO could suppress the rat PASMCs' proliferation under anoxic condition.  相似文献   

18.
AIM: To observe the kinetic alteration of nitric oxide formation in the lungs in the development of pulmonary fibrosis in the rat. METHODS: The contents of hydroxyproline in the lungs, NO2-/NO3- (nitrite/nitrate) in out-flowing and in-flowing pulmonary blood (OPB, IPB) were assayed on the day 7, 14, 21, 30 and 70 after intratracheal administration of bleomycin A5 . The content of NO2-/NO3- in supernatants of culture of the alveolar macrophages (AMs) and the amount of iNOS positive stain cells in lung tissue section were also observed in the rat on 14th day after-bleomycin A5 administration. RESULTS: The content of lung hydroxyproline had no change on the 7th day, increased on the 14th day (P＜0.05), increased significantly on the 21th day, 30th day and 70th day post-bleomycin A5 compared with control rats. On the 7th day and 14th day, the content of NO- 2 /NO3- increased in OPB and decreased in IPB (P＜0.01). On the 21th day, the content of NO2-/NO3- abated in OPB (P＞0.05) but still decreased in IPB (P＜0.01). On the 30th day and the 70th day, the NO2-/NO3- level recovered both in OPB and IPB. AMs from rats on the 14th day post-bleomycin A5 showed significant elevation (P＜0.01) in NO2-/NO3- level. The amount of iNOS positive stain cells increased in rats on the 14th day post-bleomycin A5. CONCLUSION: The amount of NO in the lungs was high in the initial phase of fibroproliferative reaction induced by bleomycin A5 ,and these might be associated with the enhanced ability of AMs to release NO and the increased amount of iNOS.  相似文献   

19.
AIM:To observe the effect of adrenomedullin(ADM)on proliferation of vascular smooth muscle cells(VSMC) induced by urotensin Ⅱ(UⅡ). METHODS:DNA synthesis of cultured rat aortic VSMC was measured by [3H]-TdR incorporation. The activities of mitogen activated protein kinase(MAPK) were determined by isotope tagged with [γ-32P]-ATP. RESULTS:UⅡ(10-8mol/L) significantly increased [3H]-TdR incorporation of VSMC and MAPK activities by 38%(P＜0.05) and 260%(P＜0.01) respectively compared with control group. Compared with UⅡ group, 10-10,10-9,10-8mol/L ADM decreased [3H]-TdR incorporation of VSMC by 7%(P＞0.05), 32%(P＜0.05)and 41%(P＜0.01),respectively, and diminished MAPK activities by 24%(P＞0.05), 32%(P＜0.05)and 36%(P＜0.05),respectively. CONCLUSION:ADM inhibits proliferation of VSMC induced by urotensin Ⅱ through inhibiting MAPK activation.  相似文献   

20.
AIM: To observe the changes of metallothionein (MT) in various tissues of mice during hyperhomocysteinemia. METHODS: Intraperitoneal injection of homocysteine into mice induced hyperhomocysteinemia. The contents of tissue MT and malondialdehyde (MDA) in liver, heart and kidney were determined. RESULTS: Compared with control group, tissue MT levels in Hcy-group animals were increased by 210% (P＜0.01) for liver, by 133% (P＜0.05) for heart and by 60% (P＜0.01) for kidney. Tissue MDA contents were increased by 6%, 52%(P＜0.05) and 69% (P＜0.05), respectively. However, in treated animals with Hcy plus superoxide dismutase (SOD), the tissue MT contents in liver, heart and kidney were decreased by 22% (P＜0.05), 33% (P＜0.05) and 13% (P＞0.05), respectively, compared with Hcy alone group. Tissue MDA contents were decreased by 24% (P＜0.05), 21% (P＜0.05) and 48% (P＜0.01). There was a positive correlation between tissue MT content and MDA level. CONCLUSION: Hcy could induce tissue MT formation through oxidative stress.  相似文献   

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