Résumé
@#Objective To observe the effects of different dosages of ginsenoside Rb1 preconditioning on spinal cord ischemia-reperfusion injury in rats, and the possible mechanism. Methods Sprague-Dawley rats were randomly divided into sham group (n=12), model group (n=12), and 10 mg/kg (D10, n=12), 20 mg/kg (D20, n=12), 40 mg/kg (D40, n=12) and 80 mg/kg (D80, n=12) drug groups. Spinal cord ischemia for ten minutes and reperfusion model was established, and the drug groups were injected ginsenoside Rb1 intraperitoneally in their dosages 30 minutes before modeling. They were assessed with BBB score 48 hours after reperfusion, and then were sacrificed for HE staining, TUNEL staining and immunohistochemistry staining of survivin.Results The BBB score was more in the drug groups than in the model group (P<0.05), and was the most in D40 and D80 groups. The expression of survivin was more in the drug groups than in the model group (P<0.05), and was the most in D40 and D80 groups. The apoptosis of neurons was less in the drug groups than in the model group (P<0.05), and was the least in D40 and D80 groups.Conclusion The ginsenoside Rb1 could promote the expression of survivin, inhibit apoptosis of neurons, to protect the neural function, in dose-dependent manner somehow.
Résumé
Objective To observe the evolution of astrocytes,GDNF,BDNF and Jak-STAT signal pathway after spinal cord ischemia-reperfusion injury in rabbits.Methods Spinal cord ischemia was induced by means of balloon occlusion of the infrarenal aorta for 22 minutes in 54 male New Zealand white rabbits.We assigned rabbits to 9 groups (n =6),one sham group,eight operation groups.The operation process in the sham group was the same as the operation group except the ischemia reperfusion of the spinal cord.At 0 h,1 h,2 h,3 h,8 h,24 h,48 h and 72 h after reperfusion,animals were sarcrificed and the spinal cord was removed for histologic,immunohistochemical study and western blotting.Results Normal neurons were decreased with the extension of reperfusion time.Levels of GFAP increased at 3 h and reached a peak at 48 h after reperfusion.GDNF was increased reaching two peaks after injury,the first peak was at 3 h,the second was at 72 h.BDNF level was increased and peaked at 24 h after reperfusion.The expression of p-STAT3 showed a biphasic pattern which peaked at 1h and 48 h.GFAP,GDNF,BDNF were rare and the level of p-STAT3 could be neglected in sham group.Conclusion Spinal cord ischemia-reperfusion injury could induce the activation of astrocytes,the expression of GDNF,BDNF and the activation of JakSTAT signal pathway.They showed different expression rules in this study.
Résumé
Objective To observe the curative effect of clinically equivalent doses of Xuesaitong and ginaton injections on cerebral ischemia reperfusion (I/R) injury of rats.Methods Male rats were randomly divided into five groups:normal control group,sham-operation group,model control group,Xuesaitong group and ginaton group.The cerebral ischemia rat model was established by middle cerebral artery occlusion (MCAO).Rats in the Xuesaitong group were given 20 mg·kg-1 of Xuesaitong injection,and rats in the ginaton group were intravenously injected with 7.5 mg· kg-1of ginaton immediately after I/R injury and once daily for 7 days.Rats in the sham-operation group and model control group were given the same volume of 0.9％ sodium chloride solution.The score of ethology,volume of cerebral infarction,mortality,superoxide dismutase (SOD),malondialdehyde (MDA),xanthine oxidase (XOD),nitrogen oxide (NO) and NO synthase (NOS) in seruu were examined.Results Compared with model control group,Xuesaitong and ginaton effectively reduced behavioral score 96 h (P ＜ 0.05),120 h (P＜0.01),144 h (P＜0.01) and 168 h (P＜0.01) after I/R injury,the volume of cerebral infarction 168 h after I/R injury and NO content (P ＜ 0.05).But they had no effects on NOS,SOD,MDA,and XOD contents.Conclusion Curatively injecting Xuesaitong and ginaton can effectively reduce cerebral I/R injury,but no significant difference in curative efficacy is observed between Xuesaitong and ginaton at clinically equivalent doses.
Résumé
Objective To investigate protective effects of thrombopoietin ( TPO) on cerebral model control in rats and associated signal transduction pathway. Methods Thread embolism was performed to generate cerebral ischemia-reperfusion rat model. Eighty male SD rats were randomly divided into sham operation group, model control group, TPO group, TPO and Janus kinase 2 ( JAK2 ) kinase inhibitor ( AG490 ) group. Before 30 min of ischemia-reperfusion, TPO group was given TPO (5 μg·kg-1) by intraperitoneal injection, TPO + AG490 group was given TPO (5 μg·kg-1) before 30 min of ischemia reperfusion, then given AG490 (8 μg·kg-1), and model control group were given the same dose of 0. 9% sodium chloride solution. The observation time points were 6, 12, 24, and 48 h after ischemia reperfusion. Immunohistochemical staining and Western blotting were used to measure the protein levels of Bcl-2, JAK2 and signal transducer & activator of transcription (STAT3). TdT-mediated dUTP nick end labeling (TUNEL) was used to detect apoptosis. Results Compared with model control group, the number of apoptotic cells were significantly reduced [(67. 50±9. 37) vs. (40. 20±7. 47)], the expression levels of Bcl-2, JAK2 and STAT3 protein were significantly increased [(35. 40±7. 39) vs. (78. 70±9. 75);(35. 68±6. 75) vs. (62.35±7.53); (25.40±9.45) vs.(55.36±9.69), respectively] 24 h after ischeia reperfusion in the TPO group (all P<0. 05). Compared with the TPO group, the Bcl-2, JAK2 and STAT3 protein levels were significantly decreased in TPO and AG490 group [(78. 70±9. 75) vs. (55. 40±9. 35);(62. 35±7. 53) vs. (40. 68±5. 89); (55. 36±9. 69) vs. (30. 40±9. 39), respetively], and the number of apoptotic cells was significantly increased [(40. 20±7. 47) vs. (55. 23±7. 65)] (all P<0. 05). Conclusion TPO can inhibit cell apoptosis after ischemia-reperfusion injury, the mechanism might be related to the activation of JAK2/STAT3 signal transduction pathway through raising the expression of Bcl-2 gene.
Résumé
Objective To investigate the effect of clotrimazole on apoptosis of hepatic cells after ischemia-reperfusion injury and its mechanism. Methods Hepatic ischemia-reperfusion rat model was established. Thirty-two male Sprague-Dawley rats were randomly allocated into sham-operated group, model control group, low dose clotrimazole group and high dose clotrimazole group. Apoptosis in hepatic tissue was assessed by TUNEL method. Protein expression levels of CYP3A1,Bcl-2,Bax and PARP were measured by Western blotting. Results As compared with model control group, the apoptosis rate, tissue injury,activity of plasma enzymes and the Bax/Bcl-2 expression ratio were reduced in low and high dose clotrimazole groups. The apoptotic index in both clotrimazole-treated groups was lower than that of model control group with statistically significant difference. CYP3A1 expression was significantly induced by clotrimazole compared to the sham-operated group. Conclusion Clotrimazole may inhibit apoptosis of hepatic cells by up-regulating Bcl-2 and down-regulating Bax, thus produce a protective effect on hepatic ischemia-reperfusion injury and it is also related to the inhibition of PARP shear.
Résumé
Objective To investigate potential effect and mechanism of dexamethasone ( DEX) on intestinal ischemia reperfusion injury. Methods A total of 18 male C57BL/6 mice were randomly divided into three groups( n=6 each): sham operation group, model control group , and DEX group. Mice in the model control and sham operation groups received intraperitoneal normal saline 0. 5 hour before ischemia, and mice in DEX group received intraperitoneal injection of DEX 10 mg·kg-1 , 0. 5 hour before ischemia. Mice in the model control and DEX groups were placed in the 32 degree infant incubator for 30 minutes after clamping superior mesenteric artery, followed by clamps removal and reperfusion for 24 hours. Mice were then sacrificed to obtain the intestinal tissues. The pathology of intestinal tissues was observed after hematoxylin-eosinstaining ( HE) staining. The mRNA expression level of pro-inflammatory cytokines IL-6, TNF-α and IFN-γ were measured by PCR. The expression of AKT and p-AKT were measured by Western blotting. Results The level of mesenteric injuries in the sham operation group, model control group and DEX group was (4±2),(13±3),(7±2) points, respectively. The mRNA level of IL-6, TNF-α and IFN-γ and the expression of p-AKT were all higher in the model control group. Compared to the model control group, the level of mesenteric injuries, the mRNA level of IL-6, TNF-αand IFN-γin DEX group were significantly attenuated, but the expression of p-AKT were further increased. Conclusion Pretreatment with DEX can reduce intestinal ischemia-reperfusion injury by activating AKT signaling pathway and suppressing inflammation.
Résumé
@#ObjectiveTo observe effects of intravenous magnesium sulfate (MgSO 4) administration on ischemia reperfusion injury of the spinal cord in rabbits.MethodsNew Zealand White rabbits (n=27) were randomly divided into the group A (treated with MgSO4), group B (treated with saline) and group C (sham group) with 9 animals in each group. Ischemic model was established with midline laparotomy and clamping the aorta just distal to left renal artery and proximal to aortic bifurcation for 30 min followed by a reperfusion period of 48 h. Animals were treated with 0.25 ml/kg/h MgSO4 intravenous infusion in group A, treated with similar volume of saline as control in group B, and were anesthetized and subjected laparotomy without aortic occlusion in group C. Somatosensory evoked potentials (SEP) were monitored before ischemia, during ischemia and in the first 60 min of reperfusion. The neurological outcome was clinically evaluated up to 48 h post ischemia, and motor function was scored. The animals were sacrificed two days post ischemia, and spinal cords were processed for histopathological examination.ResultsSEP amplitudes and latencies in group C did not change during the procedures and all animals recovered without neurological deficits. The waves disappeared in group B and reduced to 29% of the initial amplitude at the end of the ischemia in group A. After 60 min reperfusion, SEP amplitudes returned gradually to 74% and 49% of the initial amplitude respectively (P<0.01) in groups A and B. The N1, P1 latencies returned gradually to (28.9±1.9) ms, (57.3±3.2) ms in group A and (30.7±0.9) ms, (61.2±2.9) ms in group B (P<0.05). The average motor function score in group A was significantly higher than that in group B at 24 h and 48 h after reperfusion (P<0.01).ConclusionMgSO4 intravenous infusion may relieve spinal cord injury and preserve neurological function in transient spinal cord ischemia in rabbits.