贝那普利对肝纤维化大鼠NOX4和Nrf2的影响

Effect of benazepril on NOX4 and Nrf2 in rats with hepatic fibrosis

目的探讨贝那普利对肝纤维化大鼠NOX4和Nrf2的影响及其抗纤维化的机制。方法22只清洁级健康雄性SD大鼠随机分为3组:对照组6只,模型组和治疗组各8只。模型组和治疗组皮下注射40%四氯化碳油剂,建立大鼠肝纤维化模型,对照组予等剂量的油剂皮下注射,均为2次/周,共8周;在造模同时,治疗组予贝那普利10 mg/(kg·d)灌胃,其余两组予等剂量生理盐水灌胃,共8周。免疫组织化学法测定肝组织中NOX4和Nrf2的水平。结果与对照组相比,模型组肝组织中NOX4和Nrf2阳性蛋白的平均光密度值升高(NOX4:0.095±0.008 vs 0.212±0.007;Nrf2:0.073±0.005 vs 0.154±0.008),差异有统计学意义(P<0.05);与模型组相比,治疗组肝组织NOX4阳性蛋白平均光密度值降低(0.212±0.007 vs 0.150±0.004),Nrf2阳性蛋白平均光密度值升高(0.154±0.008 vs 0.177±0.007),差异均有统计学意义(P<0.05)。结论贝那普利可能通过降低NOX4的水平和升高Nrf2的水平减轻肝纤维化的程度。

Objective To explore the effect of benazepril,an angiotensin-converting enzyme inhibitor,on NOX4 and Nrf2 in rats with liver fibrosis and the mechanism of anti-fibrosis of benazepril.Methods Twenty-two healthy male SD rats of clean grade were randomly divided into three groups:control group(n=6),model group(n=8)and benazepril group(n=8).The rats in model group and benazepril group were subcutaneously injected with 40%carbon tetrachloride oil to establish liver fibrosis models,and the rats in control group were subcutaneously injected with the same dose of oil twice a week for 8 weeks.At the same time of modeling,the rats in benazepril group were intragastrically administered with benazepril 10 mg/(kg·d)and the rats in the remaining two groups were intragastrically administered with an equal dose of normal saline until the 8 th week.The levels of NOX4 and Nrf2 in liver tissues were determined by immunohistochemistry.Results Compared with control group,the mean optical density values of NOX4 and Nrf2 positive proteins in liver tissues in model group were increased(NOX4:0.095±0.008 vs 0.212±0.007;Nrf2:0.073±0.005 vs 0.154±0.008,all P<0.05).Compared with model group,the mean optical density of NOX4 positive protein in liver tissues in benazepril group was decreased(0.212±0.007 vs 0.150±0.004,P<0.05),and the mean optical density of Nrf2 positive proteins was increased(0.154±0.008 vs 0.177±0.007,P<0.05).Conclusion Benazepril can reduce the degree of liver fibrosis by decreasing the level of NOX4 and increasing the level of Nrf2.