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1.
LIU Si-hong  KONG Tian-han 《园艺学报》2006,22(12):2453-2457
AIM:In order to substitute antivenom from horse, the biologic activity and preparing methods were investigated in immunoglobulin yolk (IgY) of anti-cobra. METHODS:Leghorn hens were immunized with cobra venom. The methods of three stages，water dilution- ammonium sulfate salting out- anion exchange chromatogram, were used to purify IgY. SDS- PAGE was used to measure the purity of antibody. The titer variety of IgY was observed by indirect ELISA and double immunodiffusion. The method of pre-incubating the venom and IgY in vitro was used to test the protective effect of IgY. RESULTS:The total protein recovery rate of IgY fraction through water dilution method（IgY-WD）followed by 60% ammonium sulphate deposited (IgY-AS) was 40.36%. When applied to DEAE chromatogram further, the total protein recovery rate reduced to 14.86%, but the titer increased by 24 times. When venom at dose of 1.24 mg/kg (2×LD50) was injected into mice intraperitoneally, all the animals died within 24 h, but when pre-incubated with 2.28 mg/kg of IgY before venom treatment, all animals survived. CONCLUSION:Taking the original cobra venom as antigen, and using the water dilution-salting out- DEAE chromatogram method for purification, high purity IgY can be withdrew from the yolk.  相似文献   

2.
AIM：To explore the analgesic effect of active component from cobra venom in Wannan area. METHODS：The active component was purified from crude venom of cobra by cation-exchange chromatography and size-exclusion chromatography. The purity and molecular weight of the active component were determined by SDS-polyacrylamide gel electrophoresis and capillary zone electrophoresis. The analgesic activity was analyzed by hot-plate test and acetic acid writhing test. Normal saline and morphine were used as controls. RESULTS：A single active component was obtained from crude cobra venom. The molecular weight was about 6 500 D. The analgesic effect of the active component persisted from 0.5 h to 8 h after hot-plate test. With intraperitoneal injection of the active component at doses of 0.03 mg/kg, 0.1 mg/kg and 0.3 mg/kg in mice, the writhing inhibition rates were 27%, 50% and 70%, respectively. No statistical difference between 0.3 mg/kg group and morphine group was observed. CONCLUSION：The active component from crude cobra venom has a dose-dependent analgesic effect.  相似文献   

3.
AIM:To study the protective effect of grape seed proanthocyanidin (GSP) on nephrotoxicity induced by cisplatin (CP) in mice. METHODS:Male C57 mice were randomly divided into 4 groups: control group (N group, n=10), CP group (intraperitoneal injection of CP at dose of 20 mg/kg, n=20), GSP group (intragastric administration of GSP at dose of 500 mg/kg, n=15) and CP+GSP group (intragastric administration of GSP 30 min prior to intraperitoneal injection of CP and intragastric administration of the same dose of GSP 72 h later, n=20). On the 5th day after CP treatment, blood and kidney samples were collected. The renal pathological changes were examined by HE staining. The protein expression of glucose-regulated protein 78 (GRP78) and phosphorylated extracellular signal-regulated kinase (p-ERK) was examined by Western blotting and immunohistochemical staining. RESULTS:Renal index, blood urea nitrogen and serum creatinine were significantly higher in CP group than those in N group. The renal tissues were heavily damaged in CP group. The protein expression of GRP78 and p-ERK increased in CP group compared with N group. GSP treatment alleviated the increase in the renal index, blood urea nitrogen and serum creatinine. The damages of the renal tissues were attenuated. The protein expression of GRP78 and p-ERK was obviously reduced in CP+GSP group compared with CP group. CONCLUSION:GSP prevents kidney from CP-induced damage by suppression of endoplasmic reticulum stress.  相似文献   

4.
AIM: To investigate the ability of Chinese cobra snake venom-metalloproteinase (MT) to induce the histamine release from human mast cells and its potential mechanisms. METHODS: MT was purified from the snake venom by using heparin agarose and Superdex75 chromatography. Mast cells were dispersed from human lung, colon and tonsil tissues after digestion with collagenase and hyaluronidase. The dispersed mast cells were then challenged with MT, stimulus and control in LP4 tubes for 15 min at 37 ℃. A glass fibre-based fluorometric assay was used to measure histamine in the supernatants of dispersed mast cells. RESULTS: MT induced a dose-dependent release of histamine from human colon, lung and tonsil mast cells. As low as 0.03 mg/L of MT was able to stimulate significant histamine release from human colon mast cells, but a minimum of 0.3 or 30 mg/L of MT was required to stimulate a similar level of histamine release from lung or tonsil mast cells, respectively. The release of histamine from colon and lung mast cells in response to MT was maximized at 12 min following the addition of the stimulus. This was quite different from the picture of the peak histamine release from tonsil mast cells, in which histamine release was maximized at 8 min following the addition of MT. Pretreatment of cells with metabolic inhibitors and pertussis toxin reduced dramatically histamine release from human colon, lung and tonsil mast cells by MT. In exogenous Ca2+ and Mg2+ free experiments, the release of histamine induced by MT was significantly decreased. CONCLUSION: Cobra snake venom MT induces human mast cells to release histamine through a G-protein-related mechanism, which may contribute to the pathogenesis of venomous snake bite.  相似文献   

5.
AIM: In order to optimize the clinical treatment strategy for Cobra snakebite, the changes of biochemical indexes and blood gas, pathological alteration and time-effect relationship of antivenin application were observed in a rat model with Naja atra Cantor snake envenoming.METHODS: SD rats were injected with 2-4 LD50 cobra venom, and the dynamic changes of biochemical indexes, blood gas and the pathological alteration of muscles were observed at the time points of 20 to 140 min after venom injection.The anti-Cobra venom serum (antivenom/venom=125 kU/g) were injected at the time points of 40 to 120 min after snakevenom administered and the indexes above were also measured.RESULTS: After injected with 4 LD50 venom, the cardiac enzymes, liver enzymes and bilirubins in blood were increased significantly at 20th min, but the TCO2, BE and pH were decreased.Two peaks of cardiac enzymes, liver enzymes and bilirubins were detected at 60th min and 120th min.The peak values of AST, CK and CK-MB were significantly higher than the values at 0 min (P<0.05).The markedly widespread cloudy swelling, coagulation necrosis and inflammatory cell infiltration were observed in the sections of myocardium and skeletal muscles at the time point of 40th min after injection of 4 LD50 venom.The peak values of some indexes in the animals injected with 2 LD50 venom were lower and delay onset than those in the animals injected with 4 LD50 venom.The protective rate in the rats injected with 4 LD50 venom was elevated to 60% or more when the antiserum treatment was conducted before the first peak of cardiac enzymes in blood. However, the therapeutic effect of antiserum was not effective as the rats received the treatment after the second peak of cardiac enzymes in blood.CONCLUSION: The bimodal variation of cardiac, liver enzymes and related indicators is observed in the rat model of snake envenomin.The animals can be effectively protected by the antivenom administered before observing the second peak of cardiac enzymes in blood.  相似文献   

6.
AIM: To observe the effect of captopril on the genesis and development of gastric cancer, and to explore its clinical treatment feasibility for gastric cancer. METHODS: The human gastric cancer cell line AGS was used to establish a tumor model in nude mice, and the model mice were randomly divided into 3 groups: positive control (5-fluorouracil) group, normal control (saline) group and experimental (captopril) group. After intraperitoneal injection or intragastric administration of the drugs, the tumor growth curve was determined, and the tumor tissues were also sampled to detect the expression of Ki-67, STAT3, Bax and Bcl-2 by real-time quantitative PCR and immunohistochemistry. The apoptosis was detected by TUNEL+DAPI staining. RESULTS: The tumor growth curve showed that the tumor model in the nude mice was successfully established. The tumor volumes among groups showed significantly different after 14 d growth. The increase in the tumor volume in normal control group was significantly faster than that in the other two groups, and that in positive control group was the slowest. The expression of Bax in captopril group increased, and the expression of STAT3, Ki-67 and Bcl-2 was reduced as compared with normal control group and positive control group. Compared with normal control group, the apoptotic rate increased significantly, and the protein expression of p-STAT3 and STAT3 decreased obviously in positive control group and captopril group. CONCLUSION: With better feasibility, angiotensin-converting enzyme inhibitor captopril has a significant effect on treating gastric cancer in the AGS nude mouse model by regulating the expression of STAT3, Bax, Bcl-2 and Ki-67 to accelerate the apoptosis of cancer cells, thus inhibiting tumor growth.  相似文献   

7.
AIM：To study the effects of betaine on glial fibrillary acidic protein (GFAP), glycine (Gly) and glycine receptor (GlyR) expression in the hippocampus of rats with epilepsy induced by pentylenetetrazole (PTZ). METHODS：Forty-eight healthy male Wistar rats were randomly divided into control group, PTZ (35 mg·kg-1·d-1, intraperitoneal injection) group, PTZ+betaine (450 mg·kg-1·d-1, intragastric administration) group, PTZ+betaine (225 mg·kg-1·d-1, intragastric administration) group, PTZ+betaine (112.5 mg·kg-1·d-1, intragastric administration) group and PTZ+sodium valproate (200 mg·kg-1·d-1, intragastric administration) group. The rats in control group were intraperitoneally injected with saline at the same volume as PTZ injection, and those in control group and PTZ group received intragastric administration of saline at 1.0 mL·d-1. Rat behavior was recorded. Serum homocysteine (Hcy) level was measured. The expression of GFAP in the hippocampus was measured by immunofluorescence. Hippocampal Gly content was measured by an amino acid analysis system. The expression of GlyR was detected by immunofluorescence and Western blotting. RESULTS：There was no difference in the latency of grand mal seizures among groups (P>0.05). However, betaine treatment significantly decreased the duration of the first grand mal seizure compared with PTZ group (P<0.01). Serum Hcy level in PTZ group was significantly lowered compared with control group (P<0.01), and further decreased after betaine treatment (P<0.05). GFAP in PTZ group was significantly higher than that in control group (P<0.01), and decreased after betaine treatment (P<0.05). Gly in PTZ group was significantly lowered compared with control group (P<0.01), and increased after betaine treatment (P<0.05). The content of GlyR among groups showed the same trend as Gly. CONCLUSION：Betaine treatment shows antiepileptic effect, which may be related to its effects on the metabolites of Hcy and Gly.  相似文献   

8.
AIM:To determine which species of snake venoms contained protein c activator among 9 species of Chinese snake venoms. METHODS: Anticoagulant activity was examined by activated partial thromboplastin time (APTT) assay,and amidolytic activity was measured with activated protein c (APC) specific chromogenic peptide substrate-chromozy APC. RESULTS: Among 9 species of Chinese snake venoms,Trimeresurus mucrosquamatus venom and Agkistrodon halys venom were not only able to generate amidolytic activity from purified human PC, but also prolonged APTT strongly even at such a concentration as 1.5 mg/L. CONCLUSION:Trimeresurus mucrosquamatus venom and Agkistrodon halys venom contain protein c activator which activating human plasma PC into APC.  相似文献   

9.
AIM:To explore the effects of bone marrow-derived mesenchymal stem cells-conditioned medium (MSCs CdM) on lipopolysaccharide (LPS)-induced acute lung injury. METHODS:Lung injury was induced in mice by intraperitoneal injection of LPS. The mice were given a tail vein injection of MSCs CdM or normal saline 1 h after LPS administration. The mice were killed by an intraperitoneal injection of pentobarbital 6 h after LPS injection for either bronchoalveolar lavage fluid (BALF) and serum collection or lung histological analysis. RESULTS:Compared with control group, the BALF levels of protein, interleukin-10 (IL-10) and keratinocyte growth factor (KGF), the serum levels of tumor necrosis factor α (TNF-α) and IL-6, and the myeloperoxidase (MOP) activity in the lung tissues were significantly higher in LPS group, and severe pathological damages in the lung tissues were also observed. Treatment with MSCs CdM significantly reduced the BALF prtein level, the seum TNF-α and IL-6　levels and the lung MPO activity, and attenuated the lung pathological damages, but further increased the levels of IL-10 and KGF in the BALF. CONCLUSION:Treatment with MSCs CdM attenuates the lung injuries induced by LPS, which may be via regulating the expression of TNF-α, IL-6, IL-10 and KGF.  相似文献   

10.
AIM: To investigate the effect of purifried L-amino acid oxidase (LAO) from bungarus fasciatus snake venom on apoptosis and growth of HUVCE cell line. METHODS: The L-amino acid oxidase was purified by SP-sepharose HP column followed by Heperin-Sepharose (FF) column. The homogeneity of the preparation was examined by SDS-PAGE and the molecular weight of LAO was determined by SDS-PAGE and high performance liquid chromatography (HPLC) gel-filtration. The MTT assay was used to detect the viability of cells. Flow cytometry and laser confocal microscopy were used to identiyfy the cell cycle and apoptotic morphology after cells treated with LAO. RESULTS: An L-amino acid oxidase (BF-LAO) was successfully purified from the venom of bungarus fasciatus. It showed a single band in SDS-PAGE under both reduced and non-reduced conditions. The apparent molecular weight was determined to be 60 kD by SDS-PAGE and 70 kD by HPLC gel filtration. LAO inhibited growth and induced apoptosis of HUVCE cell line in a dose-dependent manner after 12 h incubation, with the 50% inhibitory concentration (IC50) being of 2.8 mg/L. Flow cytometry and laser confocal microscope showed a typical apoptotic peak and morphological changes of these cells. CONCLUSION: The L-amino acid oxidase from bungarus fasciatus snake venom could inhibit the HUEVC cell growth and induce the cell apoptosis.  相似文献   

11.
AIM：To investigate whether the panaxadiol saponins (PDS) and dexamethasone (DEX) have similar effects on lipopolysaccharide (LPS)-induced acute kidney injury (AKI). METHODS：C57BL/6 mice were randomly divided into 4 groups: the control mice received intraperitoneal injection of normal saline; in LPS group, the mice were subjected to intraperitoneal injection of LPS (10 mg/kg); in PDS + LPS group and DEX + LPS group, the mice were injected intraperitoneally with PDS (25.0 mg/kg) and DEX(2.5 mg/kg) 1 h before LPS injection, respectively. The blood was collected from the hearts, and the kidneys were collected for the biochemical and Western blotting analysis 12 h after LPS injection. RESULTS：LPS induced AKI, evidenced by markedly increased blood urea nitrogen (BUN) and creatinine (CREA) contents compared with control group (P<0.01). However, serum contents of CREA and BUN obviously reduced in PDS + LPS group and DEX + LPS groups compared with LPS group (P<0.05). Both PDS and DEX decreased the production of TNF-α and IL-6 by inhibiting renal NF-κB signaling activation. PDS and DEX also down-regulated the expression of inducible nitric oxide synthase, up-regulated the expression of manganese superoxide dismutase and reduced oxidative stress in the kidneys of LPS-challenged mice. In addition, treatment with PDS and DEX significantly increased the nuclear glucocorticoid receptor in the kidneys of LPS-treated mice. CONCLUSION：PDS and DEX have inhibitory effects on LPS-induced AKI mice. However, it is unclear whether PDS reduces LPS-induced AKI via direct action on glucocorticoid receptor.  相似文献   

12.
AIM: To observe the effects of normal mesenteric lymph (NML) on the lung, heart and liver injuries and the phosphorylation levels of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK) in the mice with endotoxic shock (ES). METHODS: The NML was drained form health male BALB/c mice for the intervention of ES after the removal of cellular constituent. Lipopolysaccharide (LPS, 35 mg/kg) was intraperitoneally injected into the mice for the establishment of ES model. After 60 min of LPS injection, the administration of NML (1/15 of whole blood volume) was performed through the femoral artery in NML+ES group. Meanwhile, the mean arterial pressure (MAP) was monitored during the experiment. At 6 h after intraperitoneal injection of LPS or the corresponding time point, blood samples were harvested from the heart through apical centesis for determination of the biochemical indexes to reflect myocardial and hepatocyte injuries. Simultaneously, the lung, heart and liver tissue specimens from a fixed location were harvested for the observation of histomorphology and the measurement of phosphorylation levels of p38 MAPK, ERK1/2 and JNK. RESULTS: Compared with sham shock (SS) group, MAP in ES group and NML+ES group remarkably decreased at multiple time points after intraperitoneal injection of LPS. However, MAP in NML+ES group at 80 min, 90 min, 190 min, 210 min, 240 min, 250 min, 340 min, 350 min, and 360 min were significantly increased compared with ES group. There were normal structures in the lung, liver and myocardium of the mice in SS group, while the morphological damages of these tissues appeared in ES group. Meanwhile, the damages were attenuated in the mice of NML+ES group. The activities of AST, ALT and CK-MB in the plasma in ES group were remarkably higher than those in SS group. The CK-MB activity in NML+ES group was also increased compared with SS group, and the activities of AST and LDH-1 were lower than those in ES group. At 6 h after LPS injection, the phosphorylation levels of p38 MAPK, ERK1/2 and JNK in the lung tissues were remarkably increased. Meanwhile, no statistical difference of these indexes between the myocardial and hepatic tissues was observed. NML intervention decreased the phosphorylation levels of p38 MAPK in the lung tissues, and p38 MAPK, ERK1/2 and JNK in the myocardial tissues. CONCLUSION: The NML administration alleviates multi-organ injuries and reduces the phosphorylation level of p38 MAPK in the lung tissues in the mice subjected to ES.  相似文献   

13.
AIM：To establish the animal model of insulinoma and to analyze the properties of insulinoma for further study. METHODS：The hormone-releasing ability of rat insulinoma cell line INS-1 was detected in vitro. INS-1 cells were transplanted into the left kidney capsule of nude mice. The islets of the animals were destroyed by intraperitoneal injection of streptozocin (STZ) 3 d before transplantation or 2 weeks after transplantation. The venous blood was sampled, and the level of blood glucose less than 2.8 mmol/L was defined as successful establishment of insulinoma model. Different irritants were given to the model animals, and the changes of blood glucose and insulin content in serum were observed. The pancreatic tissues and the renal tissues in the injecting sites were taken from all mice for detecting insulin and glucagon by immunohistochemical staining. RESULTS：Insulinoma cells expressed insulin and glucagon at the same time. The blood glucose was less than 2.8 mmol/L 3 to 4 weeks after inoculation of INS-1 cells. Apparent tumor formed in the left kidneys where INS-1 cells were transplanted and the tumor diameters were more than 1 cm. The level of blood glucose transiently increased to higher than the normal level in the mice with tumor cell transplantation after intraperitoneal injection of STZ, and then decreased gradually and returned to less than 2.8 mmol/L after 2 weeks. The level of blood glucose in the normal nude mice after administration of STZ increased significantly. After transplantation of INS-1 cells, the level of blood glucose decreased gradually, and returned to less than 2.8 mmol/L after 4 weeks. After stimulated with high glucose, the blood glucose levels in the mice with 3 methods to establish the insulinoma models showed lower glucose peaks than that in the normal control mice. After stimulated with high glucose plus arginine or acetylcholine in the normal animals, the blood glucose peak was lower than that in the normal animals only stimulated with high glucose, and rapidly recovered to the normal level. However, the levels of blood glucose in the mice with 3 methods to establish the insulinoma models under the same stimulations were significantly higher than that in the mice only stimulated with high glucose. After stimulated with high glucose plus norepinephrine, the blood glucose peak time in the normal animals delayed, and the blood glucose level declined slowly. After stimulated with high glucose plus norepinephrine, the levels of blood glucose in the mice with 3 methods to establish the insulinoma models increased as compared with that in the mice only stimulated with high glucose. Compared with normal control group, serum insulin in insulinoma mice increased significantly. CONCLUSION：The insulinoma animal model is successfully established by transplantation of INS-1 cells into the renal capsule of nude mice. The insulinoma cells express both insulin and glucagon, and are not easily damaged by STZ.  相似文献   

14.
AIM: To investigate the anti-tumor efficacy of angiogenic inhibitor three hrombospondin-1 type repeats (3TSR) on gastric cancer. METHODS: Human gastric carcinoma cell line SGC-7901 was inoculated subcutaneously to BALB/c mice, and then the mice were divided into two groups (8 mice each): control group and 3TSR group. After administration of 3TSR by intraperitoneal injection for 3 weeks, mice were sacrificed. The tumor volume and percentage of necrotic area were detected. The micro-vessel index and cell proliferation index were detected by immunohistochemistry method. The apoptosis rate of gastric carcinoma cells was measured by TUNEL method. The vascular endothelial cell apoptosis rates were detected by CD31/TUNEL/DAPI staining. RESULTS: The tumor volume in 3TSR group was (648.34±126.91)mm3, significantly lower than that in control group (P<0.05). The percentage of tumor necrosis area in 3TSR group was (39.6±7.8)%, almost increased by 69.2% than that in the control. Average micro-vessel numbers and micro-vessel area in 3TSR were 12.8±4.1 and (689.3±118.6) μm2, respectively, significantly lower than those in the control. The proliferation index and apoptosis rate in 3TSR group were (40.0±7.1)% and (3.4±1.2)%, respectively. No difference between 3TSR group and the control was observed. The endothelial cell apoptosis rate in 3TSR group was (11.6±2.8)%, significantly higher than that in control group (2.9±1.5)%. CONCLUSION: 3TSR inhibits tumor angiogenesis, remarkably reduces tumor volume, average micro-vessel and increased tumor necrosis. 3TSR shows no direct inhibitory effects on gastric cancer cells. The antiangiogenesis effects of 3TSR on gastric carcinoma may be due to the induction of apoptosis of vascular endothelia cells.  相似文献   

15.
AIM：To investigate the changes of light response and visual behavior after transfecting intrinsic photosensitive protein melanopsin (opsin 4, Opn4) into ON-bipolar cells in a mouse retinal degeneration model. METHODS：N-methyl-N-nitrosourea (MNU)-induced CD1 mice served as the retinal degeneration model. CD1 mice on postnatal day 0 (P0) and postnatal day 1 (P1) were subretinally injected with Grm6-Opn4-GFP plasmid, and those injected with Grm6-GFP plasmid served as negative control group. Electroporation was applied to transfect the plasmids into cells. Five weeks later, the transfected mice received intraperitoneal injection of MNU to induce the apoptosis of photosensory cells in 7 days. The mice were divided into 5 groups：normal control group, normal saline (NS) intraperitoneal injection with Grm6-Opn4-GFP transfection (NS+melanopsin) group, MNU intraperitoneal injection with Grm6-Opn4-GFP transfection (MNU+melanopsin) group, MNU intraperitoneal injection with Grm6-GFP transfection (MNU+GFP) group and MNU intraperitoneal injection (MNU) group. Visual behavior was tested by Dark/Light Box test for 7 days after MNU injection, in which the time spending in each area of the box was measured every day for each animal. Electroretinagram was applied to measure the peak amplitude and the latency time of b-wave, and photopic negative response (PhNR), which stand for the functions of ON-bipolar cells and retinal ganglion cells, respectively. Immunohistochemistry was performed to check the expression of melanopsin in the ON-bipolar cells in the transfected retina. RESULTS：Melanopsin was specifically transfected into ON-bipolar cells and was expressed in the transfected cells. The dark/light box test showed that the mice in MNU+melanopsin group stayed significantly longer in the dark zone than those in negative control group (P<0.05). Their b-waves tended to recover as well (P<0.05 vs negative control group). CONCLUSION：Specific transfection of melanopsin into ON-bipolar cells can partially restore the visual function of mice.  相似文献   

16.
AIM: To investigate the protective effect of the bone marrow cells transfected with human multidrug resistance gene (MDR1) on the reconstruction of murine hematopoietic function.METHODS: The mononuclear cells of the bone marrow from donors, BALB/C mice, treated with 5-Fu previously, were isolated and transfected with human multidrug resistance gene in vitro , then transplanted to the tertiary recipients. After lethal irradiation(8.5 Gy) and bone marrow transplantation, the recipients were selected with Taxol 7 mg/kg intraperitoneal injection, VCR 5 mg/kg or DNA 5 mg/kg intravenous injection. The survival rate and blood pictures of mice as well as the integration and expression of target gene MDR1 were studied. RESULTS: The lethal irradiated murine hematopoietic function could be reconstructed and protected from toxicity of high doses Taxol, VCR and DNR selection after reinfusing the hematopoietic progenitor cells containing human multidrug resistance gene (MDR1). The survival rate and survival time of experimental mice were higher than that in the control group. The integration and expression of MDR1 gene in recipients were confirmed by PCR, RT-PCR and FCM. CONCLUSION: The integration and expression of human multidrug resistance gene in recipients may play an important role in the reconstruction and protection of murine hematopoietic function.  相似文献   

17.
AIM: To explore whether angiotensin Ⅱ type 2 receptor antagonist EMA401 decreases neuropathic pain and the expression of growth-associated protein-43 (GAP-43), protein kinase C (PKC) and calmodulin (CaM) in dorsal root ganglia (DRG) during chronic constriction injury (CCI) in rats. METHODS: SD rats were used to establish CCI model and randomly divided into 4 groups. The rats in model group were given equal volume of normal saline by intragastric administration. The rats in low dose (LD) group were given 5 mg/kg EMA401 by intragastric administration. The rats in middle dose (MD) group were given 10 mg/kg EMA401 by intragastric administration. The rats high dose (HD) group were given 20 mg/kg EMA401 by intragastric administration. The rats in sham operation group received equal volume of normal saline by intragastric administration. Thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) were measured before operation and 7 d, 14 d and 28 d after CCI. After behavioral test, DRG of lumbar spinal was obtained from each group, and was used to determine Ca2+ concentration by o-cresolphthalein complexone microplating method, and the expression of GAP-43, PKC and CaM at mRNA and protein levels by Western blotting and RT-PCR. RESULTS: Compared with model group, EMA401 significantly increased the TWL and MWT (P<0.05). Meanwhile, EMA401 significantly reduced Ca2+ concentration and the expression of GAP-43, PKC and CaM at mRNA and protein levels in the DRG (P<0.05). CONCLUSION: EMA401 may attenuate neuropathic pain of CCI by inhibiting Ca2+ concentration and the expression of GAP-43, PKC and CaM.  相似文献   

18.
AIM: To investigate the distribution in mice and pharmacokinetics in rabbits of fraction Ⅲ isolated from Naja naja atra venom. METHODS: Fraction Ⅲ was labelled with [125Ⅰ] by chloramine-T method. The drug concentration in blood was determined by a radionuclide tracing kinetic methods. The distribution of [125Ⅰ]-fraction Ⅲ in mice was determined based on the ratio of the relative incorporation of radioactivity in tissues to that in blood. RESULTS: In two and four hours after intravenous injection of fraction Ⅲ in mice, the organs in which the ratio of the radioactivity incorporation was bigger than 1 were liver, kidney, lung, heart and muscle, whth the maximun in kidney. After intravenous injection of fraction Ⅲ, with dosages of 75, 150 and 300 μg/kg, respectively, the T1/2α, T1/2β and T1/2γ were 39.6-42.5 min, 16.8-17.3 h and 21.7-22.1 h, respectively. There was no significant difference between the different dosages. CONCLUSION: Fraction Ⅲ was mostly found in kidney, followed by liver and lung after intravenous administration in mice. The pharmacokinetics is in accordance with the feature of three atrioventricular modle. The AUC is in direct proportion to the dosage. It suggests that the distribution and clearance of the drug is a grade 1 linear kinetic process.  相似文献   

19.
AIM: To evaluate the effect of betaine on lipid metabolism disorder in inherited db/db mice with long-term nonalcoholic fatty liver disease (NAFLD).METHODS: Experimental NAFLD models were established by feeding the db/db mice with high-fat diet. Fifty 7-month-old db/db mice were randomly divided into 5 groups: the mice in low, medium and high dose groups were given betaine by intragastric administration at doses of 200 mg/kg, 400 mg/kg and 800 mg/kg for 6 weeks, respectively,while the mice in saline control group and positive drug group were given normal saline and positive control drug,respctively. All the animals were killed, and serum alanine aminotransferase (ALT), triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL) and glucose tolerance were detected. The pathological changes of the liver tissues were also observed.RESULTS: Betaine significantly decreased the levels of ALT, TC and LDL (P<0.05 or P<0.01). The pathological changes of the liver tissues indicated that the content of lipid in the hepatocytes of betaine treatment groups was less than that in saline control group.CONCLUSION: Betaine significantly improves the lipid metabolism and the liver function in the aging db/db mice, and reduces the accumulation of lipid in the hepatocytes.  相似文献   

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