山茱萸提取物对大鼠肝脏缺血再灌注损伤的保护作用及对SIRT1-p53通路的影响

Protective effect of Fructus Corni extract on hepatic ischemia-reperfusion injury in rats and on SITR1-p53 pathway

目的探讨山茱萸提取物(FCE)对大鼠肝脏缺血再灌注损伤(HIRI)的保护作用及可能的分子机制。方法建立大鼠HIRI模型,并灌胃给予FCE预处理,使用试剂盒检测各组大鼠血清谷丙转氨酶(ALT)和谷草转氨酶(AST)水平,取肝脏组织做HE染色观察肝脏病理改变,采用Western blot检测肝脏组织中SIRT1、Ac-p53、Bax、Bcl-2和Cleaved-caspase-3等蛋白表达变化。结果与假手术组相比,模型组血清ALT和AST水平显著增加;病理切片显示肝脏组织表现出炎性细胞浸润、肝细胞坏死等现象;SIRT1表达水平减少,Ac-p53表达水平增高,导致Bax和Cleaved-caspase-3表达增加,Bcl-2表达减少(P<0.05)。与模型组相比,FCE组大鼠血清ALT和AST水平降低,肝组织炎性反应、肝细胞坏死等病理改变有明显改善,SIRT1的表达水平增加,Ac-p53的表达减少,引起Bax和Cleaved-caspase-3的表达减少,Bcl-2的表达增加。结论 FCE可能通过调控SIRT1-p53信号通路对大鼠HIRI起到保护作用。

Objective To determine the protective effect of Fructus Corni extract(FCE)on hepatic ischemiareperfusion injury(HIRI)and the relative molecular mechanism in rats.Methods After pretreatment with FCE,HIRI was induced in SD rats.The content of AST and ALT was assayed by commercial kits.The liver tissue pathology change was determined by HE staining.The protein expression of SIRT1,Ac-p53,Bax,Bcl-2,Cleaved-caspase-3 andβ-actin was assessed by Western blot.Results Compared with the Sham group,in the ischemia-reperfusion group(IR group),the levels of ALT and AST were increased,the expressions of Ac-p53,Bax and Cleaved-caspase-3 were upregulated,the expressions of SIRT1 and Bcl-2 were downregulated,and the pathological sections showed inflammatory infiltration and hepatic cell necrosis in the liver tissue.Compared with the IR group,the levels of ALT and AST were decreased,the expression of Ac-p53,Bax and Cleavedcaspase-3 were downregulated,the expression of SIRT1 and Bcl-2 were upregulated and the pathological changes such as inflammatory response of liver tissues and liver cell necrosis were significantly improved in the FCE groups.Conclusion FCE has protective effect on HIRI,which may be related to the regulation of SIRT1-p53 signaling pathway.