苦参碱通过TRAIL/BAX途径抑制大鼠肝缺血-再灌注损伤后肝细胞凋亡

摘要

目的:探讨苦参碱抑制肝脏缺血-再灌注损伤后肝细胞凋亡的分子机制.方法:选用健康成年SD大鼠50只,通过夹闭门静脉和肝动脉血流,缺血70 min后进行再灌注的方法建立HIRI模型(缺血-再灌注损伤模型).模型动物随机分为两组,实验组(MT组)大鼠在夹闭门静脉和肝动脉前经门静脉主干注入苦参碱30 mg/kg,对照组(NS组)注入生理盐水3 mL/kg.阻断血流1h后恢复再灌注,在恢复再灌注2h后采集血、肝组织标本行免疫组织化学及Western blot检测.结果:HE染色结果显示,MT组肝组织损伤程度较对照组轻,免疫组织化学、Western blot结果均显示,MT组TRAIL蛋白表达水平、BAX表达水平显著低于NS组.结论:TRAIL/BAX信号通路是缺血再灌注损伤引起细胞凋亡中的重要环节,苦参碱可通过抑制TRAIL/BAX信号通路,调节大鼠缺血再灌注损伤后肝细胞凋亡.%To investigate the molecular mechanism of Matrine on hepatocyte apoptosis after hepatic ischemia-reperfusion injury in rats.Methods:50 SD rats were randomly divided into the control group (n =25) and the Matrine group (n =25),HIRI(hepatic ischemia reperfusion injury) models were established by the method of clip-closed portal vein and hepatic artery for 70min then followed by reperfusion.The Matrine group was injected with Matrine(30 mg/kg) through main portal vein before modeling,whereas the control group was injected with normal saline (3 ml/kg).The blood reperfusion was carried out one hour after blocking blood supply.Blood sample and liver tissues were collected for relative tests two hours after the reperfusion.Results:HE results showed that the degree of liver damage was less in the Matrine group than that in the control group.Both immunohistochemistry test and Western blot results showed that the expression levels of TRAIL protein and BAX were significantly lower in the Matrine group than those in the control group.Conclusion:TRAIL/BAX signaling pathway is an important link of cell apoptosis in ischemia-reperfusion injury,Matrine can regulate the hypatocyte apoptosis after ischemia-reperfusion injury in rats,by inhibiting the TRAIL/BAX signaling pathway.