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Objective To evaluate the effect of propofol on high-mobility group box 1 protein (HMGB1)/Toll-like receptor 4 (TLR4) signaling pathway during hepatic ischemia-reperfusion (I/R) injury in rats.Methods Thirty-six clean-grade healthy male Sprague-Dawley rats,aged 3 months,weighing 250 -300 g,were divided into 3 groups (n=12 each) using a random number table method:sham operation group (group S),hepatic I/R group (group I/R) and propofol group (group P).Hepatic I/R injury was induced by occluding the portal vein and hepatic artery supplying the left and middle lobes of the liver for 1 h followed by 6-h reperfusion in anesthetized rats.Propofol was infused via the tail vein at a rate of 12 mg ·kg-1 · h-1 starting from 20 min before ischemia until 6 h of reperfusion in group P.The rats were sacrificed at 6 h of reperfusion,and the left lobe of the liver was removed for microscopic examination of the pathological changes which were scored and for determination of the expression of HMGB1,TLR4,tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-6) in liver tissues (by Western blot).Results Compared with group S,pathological scores of liver tissues were significantly increased,and the expression of HMGB1,TLR4,TNF-α and IL-6 was up-regulated in I/R and P groups (P＜0.05).Compared with group I/R,pathological scores of liver tissues were significantly decreased,and the expression of HMGB1,TLR4,TNF-α and IL-6 was down-regulated in group P (P＜ 0.05).Conclusion The mechanism by which propofol reduces liver I/R injury is associated with blocking HMGB-1/TLR4 signaling pathway and inhibiting inflammatory responses in rats.
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Objective To evaluate the effect of sevoflurane postconditioning on autophagy during focal cerebral ischemia-reperfusion (I/R) in rats.Methods Forty-five clean-grade healthy male SpragueDawley rats,weighing 280-350 g,were divided into 3 groups (n=15 each) using a random number table method:sham operation group (S group),cerebral I/R group (I/R group) and sevoflurane postconditioning group (SP group).Focal cerebral I/R injury model was established by Zea-Longa method in chloral hydrate-anesthetized rats.The animals in SP group inhaled 2.4％ sevoflurane for 30 min starting from onset of reperfusion.The expression of autophagy-related proteins LC3 and beclin-1 was detected by Western blot at 2 h of reperfusion.The cerebral cortex was removed for examination of the morphology and number of autophagosomes with an electron microscope.Neurological deficit was assessed and scored at 24 h of reperfusion.Rats were sacrificed at 72 h of reperfusion for determination of the cerebral infarct size.Results Compared with S group,the neurological deficit score was significantly increased,the percentage of cerebral infarct size was increased,LC3Ⅱ/LC3Ⅰ ratio in cerebral cortex was increased,the expression of beclin-1 was up-regulated,and the number of autophagosomes was increased in I/R and SP groups (P＜0.05).Compared with I/R group,the neurological deficit score was significantly decreased,the percentage of cerebral infarct size was decreased,LC3Ⅱ/LC3Ⅰ ratio in cerebral cortex was decreased,the expression of beclin-1 was down-regulated,and the number of autophagosomes was reduced in SP group (P＜0.05).Conclusion Sevoflurane postconditioning mitigates focal cerebral I/R injury through inhibiting autophagy in rats.
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BACKGROUND:Cdh1 has been shown to express in rat hippocampus and cortex in a large number. Moreover, in vitro test demonstrated that Cdh1 expression was higher in neurons than in neural stem cel s, which possibly associated with the differentiation of neural stem cel s into neurons. However, the effects of anaphase promoting complex Cdh1 on ischemic neuronal damage remain unclear. OBJECTIVE:To investigate the expression of Cdh1 and its downstream substrate in primary cultured neurons with oxygen-glucose deprivation. METHODS:Primary neurons from cortex of postnatal 24-hour rat pups were cultured in vitro, and identified by immunofluorescence staining. The oxygen-and glucose-deprived models were established by three gas incubator fil ed with nitrogen in sugar-free Earle’s solution. After 1 hour of hypoxia, reoxygenation was conducted. Real-time fluorescent quantitative PCR was used to detect the mRNA expression of Cdh1 and its downstream substrates Skp2, Cyclin B1 before hypoxia, 6 hours, 1, 3, 7 days after oxygen glucose deprivation. RESULTS AND CONCLUSION:After oxygen glucose deprivation, the expression of Cdh1 and Cyclin B1 in primary neurons was increased (P<0.05), while Skp2 expression was decreased (P<0.05). Above data indicated that Cdh1 expression in neurons increased after oxygen-glucose deprivation. It may degrade Skp2 and participate in hypoxic neuronal apoptosis by ubiquitination.
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@#ObjectiveTo investigate the expression of APC-Cdh1 protein after cerebral ischemia-reperfusion injury.Methods60 male Sprague-Dawley rats were randomly divided into Sham-operated group(SH) and ischemia-reperfusion group(IR). The rats of ischemia-reperfusion groups were induced by four-vessel occlusion (4-VO). At different times after injury, the expression of APC-Cdh1 of rat hippocampus was observed by Western blotting and immunohistochemistry.ResultsCompared with sham-operated group, the expression of Cdh1 protein significantly decreased 1 day and increased obviously 3 days, but decreased again 7 days after injury in ischemia-reperfusion group. The immuno-staining showed that APC-Cdh1 was highly cerebral cortex and hippocampus in ischemia-reperfusion group. ConclusionAPC-Cdh1 may be involved in the central nervous system injury.