pifithrin-α抑制大鼠肝缺血再灌注早期PUMA蛋白的表达

pifithrin-alpha reduces the expression of PUMA protein in the early stage of liver ischemia-reperfusion in rats

背景:pifithrin-α是一种可逆性p53抑制剂,应用pifithrin-α抑制p53通路对肝脏缺血再灌注损伤的影响尚不清楚。目的:探讨核转录因子p53抑制剂对大鼠肝缺血再灌注后PUMA蛋白表达的影响。方法:96只雄性Wistar大鼠随机分为对照组,缺血再灌注组,缺血再灌注+二甲亚砜溶媒对照组(二甲亚砜组),缺血再灌注+p53抑制剂pifithrin组(PFT组)。建立70%肝缺血模型,PFT组于60min的肝血流阻断结束时立即给予pifithrin-α,二甲亚砜组给予等量二甲亚砜溶液,对照组和缺血再灌注组给予等量生理盐水。结果与结论:大鼠肝缺血再灌注后1,3,6h肝组织PUMA蛋白表达明显,PFT组可以明显抑制PUMA蛋白的表达,但缺血再灌注24hPFT组PUMA蛋白的表达高于其他3组。结果可见pifithrin-α对肝脏缺血再灌注损伤有一定保护作用,其通过抑制p53从而诱导PUMA蛋白表达下调主要是在缺血再灌注早期。

BACKGROUND：pifithrin-α is a reversible inhibitor of p53,the effect of pifithrin-α inhibited p53 pathway on hepatic ischemia-reperfusion injury is unclear.OBJECTIVE：To explore the effect of nuclear transcription factor p53 inhibitor on the expression of PUMA protein after liver ischemia-reperfusion in rats.METHODS：Ninety-six male Wistar rats were divided into four groups randomly：control group,ischemia-reperfusion group,ischemia-reperfusion＋solvent dimethyl sulfoxide（DMSO） group（DMSO group） and ischemia-reperfusion＋pifithrin-α group（pifithrin-α group）.The 70% liver ischemia model was established.The rats in PFT group were injected with pifithrin-α after 60 minutes,the DMSO group was injected with dimethyl sulfoxide solution and the control group and ischemia-reperfusion group were injected with normal saline in the same dose.RESULTS AND CONCLUSION：At 1,3 and 6 hours after ischemia-reperfusion in rat liver,the expression of PUMA protein in liver tissue was obviously,the expression of PUMA protein in pifithrin-α group was inhibited significantly.However,at 24 hours after ischemia-reperfusion,the expression of PUMA protein in pifithrin-α group was higher than that in the other three groups.pifithrin-α can protect liver from ischemia-reperfusion injury through suppressing p53 in the order to decrease the expression of PUMA protein,but pifithrin-α can reduce the expression of PUMA protein only in the early stage after rschemia-reperfusion.