贝那普利对肝纤维化大鼠ROS、GSH浓度及Nrf2表达的影响

Effects of benazepril on ROS and GSH concentrations and Nrf2 expression in hepatic fibrosis rats

目的研究贝那普利对肝纤维化大鼠活性氧簇(ROS)、还原性谷胱甘肽(GSH)及核因子E2相关因子2(Nrf2)的影响,探究其对肝脏的保护作用及可能机制。方法将22只健康雄性SD大鼠随机分为3组:对照组6只、模型组8只、治疗组8只。模型组及治疗组均给予皮下注射40%CCl 4油剂,对照组予以相同剂量的油剂皮下注射,2次/周;治疗组从实验开始给予贝那普利灌胃,直至实验结束,余两组均予以同剂量生理盐水。比色法测定血清GSH及ROS的浓度,real-time PCR检测肝组织Nrf2 mRNA的表达量。结果与对照组相比,模型组ROS的浓度及Nrf2 mRNA的表达量均升高,差异有统计学意义(P<0.05),GSH的浓度有升高趋势,差异无统计学意义(P>0.05)。与模型组相比,给予贝那普利治疗后,治疗组ROS的浓度降低(P<0.05),Nrf2 mRNA的表达量升高(P<0.05),GSH的浓度有升高趋势,差异无统计学意义(P>0.05)。结论贝那普利可能通过降低血清ROS的浓度、增加Nrf2的表达,减缓肝纤维化的进展以保护肝脏。

Objective To study the effects of benazepril on reactive oxygen species(ROS),reduced glutathione(GSH)and nuclear factor-related factor 2(Nrf2)in hepatic fibrotic rats,and to explore its protective effect on liver and its possible mechanism.Methods Twenty-two healthy male SD rats were randomly divided into three groups:control group(n=6),model group(n=8)and benazepril group(n=8).The rats in both model group and benazepril group were subcutaneously injected with 40%CCl 4 oil twice one week,while the rats in control group were subcutaneously injected with the same dose of oil.The rats were intragastrically administrated with benazepril from the begining to the end of the experiment in benazepril group,and the same dose of normal saline in the other two groups.The concentrations of serum GSH and ROS were determined by colorimetry,and the expression of Nrf2 mRNA in liver tissues was detected by real-time PCR.Results Compared with control group,ROS concentration and Nrf2 mRNA expression were statistically increased in model group(P<0.05),while GSH concentration tended to increase,but the difference was not statistically significant(P>0.05).Compared with model group,ROS concentration was significantly decreased in benazepril group(P<0.05),the expression level of Nrf2 mRNA was statistically increased(P<0.05),and the concentration of GSH showed no significant change(P>0.05).Conclusion Benazepril may slow down the progression of liver fibrosis to protect the liver by decreasing the concentration of ROS and increasing the expression of Nrf2.