目的:探讨姜黄素对四氯化碳(carbon tetrachloride,CCl4)诱导的大鼠肝纤维化的影响及姜黄素能否抑制肝脏NADPH 氧化酶4(NADPH oxidase 4,NOX4)的表达.方法:腹腔注射CCl4(每周2次,共6周)诱导SD大鼠肝纤维化模型.将SD大鼠随机分成4组:正常对照组(n=10)、单纯给药组(n=10)、模型对照组(n=15)和姜黄素预防组(n=1 5),姜黄素给药剂量为200 mg/kg体质量.检测血清中ALT、AST及活性氧自由基(reactive oxygen species,ROS)的水平;肝损伤和肝纤维化评估采用肝组织HE染色与天狼星红染色;分别用实时荧光定量PCR、Western blotting和免疫组织化学方法检测肝组织NOX4的表达.结果:姜黄素能减轻CCl4诱导后大鼠的肝损伤与肝纤维化,抑制血清ROS的产生.与模型对照组相比,姜黄素预防组的肝纤维化大鼠肝脏中NOX4 mRNA与蛋白表达水平显著降低.结论:姜黄素能减轻CCl4诱导大鼠发生的肝损伤与肝纤维化,其效应可能与抑制肝脏NOX4过表达有关.
Objective:The aim of this study was to investigate the effect of curcumin on liver fibrosis and hepatic expression of NADPH oxidase 4 (NOX4) in rat model.Methods:The SD rats were intraperitoneally injected with carbon tetrachloride (CCl4)twice a week for 6 weeks to induce liver fibrosis.The rats were randomly divided into four groups:normal control group (n =10),curcumin-treated control group (n =10),model control group (n =15) and curcumin prevention group (n =15).Curcumin was given at a dose of 200 mg/kg body weight daily.Serum transaminase activity and reactive oxygen species (ROS) were assessed.Hematoxylin-eosin (H&E) staining and sirius red staining were performed to evaluate liver injury and fibrosis.Moreover,the levels of NOX4 mRNA and protein expression were determined by real time-PCR,Western blotting and immunohis tochemistry.Results:Chronic CCl4 treatment caused liver injury,ROS increase,and collagen accumulation in the liver.Treatment with curcumin could significantly reduce liver injury,fibrosis and ROS.Furthermore,curcumin significantly attenuated the expression of NOX4 in liver.Conclusions:Curcumin significantly attenuates the severity of CCl4-induced liver injury and fibrosis,and the beneficial effects may be partly through inhibition of hepatic NOX4 expression.