大麻二酚对小鼠肝缺血再灌注损伤的保护作用研究

Research on the protection effects of Cannabidol in rats with Doxorubicin-induced hepatic ischemia reperfusion injury

目的研究大麻二酚(Cannabidiol,CBD)对肝脏缺血再灌注损伤的保护作用及其机制。方法利用小鼠肝脏缺血再灌注损伤动物模型,通过蛋白印迹法、Realtime PCR、ELISA等多种方法研究肝脏缺血再灌注损伤过程中血清谷丙转氨酶(ALT)、谷草转氨酶(AST)变化;肝脏组织损伤;肝脏组织中iNOS、TNF-α、MIP-1α、MIP-2的表达;DNA片段化、PARP活性测定;肝脏组织中MPO、硝基酪氨酸含量改变,以及CBD处理对上述指标的改变。结果在小鼠肝脏缺血再灌注损伤过程中,小鼠肝功能指标升高(ALT、AST),肝脏组织中炎症相关因子指标上升(MPO水平,TNF-α,MIP-1α、MIP-2表达),氧化应激损伤(iNOS表达、MDA水平、硝基酪氨酸含量),细胞死亡指标上升(DNA片段化,caspase3,8,9表达测定)等,导致肝脏组织损伤。而CBD能下调缺血再灌注导致肝脏组织内炎症相关因子表达,减轻了氧化应激损伤及细胞凋亡,并减轻肝脏组织损伤。结论CBD能减轻小鼠肝脏缺血再灌注损伤,其保护作用与上述机制相关。

Objective To explore the protection effects of Cannabidol in rats with Doxorubicin-induced hepatic ischemia reperfusion injury and its mechanism.Methods In this study,we used various molecular biology and biochemistry methods(Western blot,Realtime PCR,ELISA)in mice model of Doxorubicin-induced hepatic ischemia reperfusion injury.Results Doxorubicin-induced hepatic ischemia reperfusion injury was evident by elevation of serum CK,LDH levels.The damage was also marked by the increase in oxidative/nitrodative stress,as well as cell death markers such as caspase 3,8,9 and inflammatory cytokines(TNF-α,IL-1β)expression.Doxorubicin-induced hepatic ischemia reperfusion injury was attenuated by Cannabidol administration by decreased ROS production(Declined NAPDH oxidase,iNOS expression),caspase and inflammatory cytokines expressions.Conclusion Cannabidol may represent a novel hepatic protective strategy against doxorubicin-induced hepatic ischemia reperfusion injury.