机构地区:[1]卫生部北京医院卫生部北京老年医学研究所,北京100730 [2]河北联合大学基础医学院组织学与胚胎学教研室,河北唐山063000 [3]开滦医疗集团林西医院妇产科,河北唐山063000 [4]中国医学科学院北京协和医学院医药生物技术研究所肿瘤室,北京100050
出 处:《吉林大学学报(医学版)》2015年第2期225-229,I0001,共6页Journal of Jilin University:Medicine Edition
基 金:国家自然科学基金资助课题(81170409;81101720);卫生部国家"重大新药创制"科技重大专项资助课题(2012ZX09301002-001);河北联合大学大学生创新性实验计划资助课题(X2014078)
摘 要:目的:观察姜黄素对实验性肝纤维化大鼠肝损伤的保护作用,并探讨其作用机制。方法:采用胆管结扎法诱导大鼠肝纤维化模型,将21大鼠随机分为假手术组(不建模,只给予生理盐水)、肝纤维化模型组(建模后给予生理盐水)和姜黄素给药组(建模后给予姜黄素400mg·kg-1),每组7只,给药2周后检测大鼠血清中丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)活性和总胆红素(Tbil)水平;HE染色观察大鼠肝脏组织病理形态学;Massion染色观察大鼠肝脏组织胶原沉积;Western blotting法检测大鼠肝脏组织中转化生长因子β1(Tgf-β1)和α-平滑肌肌动蛋白(α-Sma)表达水平。结果:与假手术组比较,肝纤维化模型组和姜黄素给药组大鼠血清中ALT、AST活性和Tbil水平明显升高(P<0.05);与肝纤维化模型组比较,姜黄素给药组大鼠血清中ALT、AST活性和Tbil水平明显降低(P<0.05)。肝纤维化模型组大鼠肝脏组织明显破环,大量炎症细胞浸润、胶原沉积及胆管增生,姜黄素给药组大鼠肝纤维病理变化明显减轻。Western blotting检测,与假手术组比较,肝纤维化模型组大鼠肝脏组织中Tgf-β1和α-Sma蛋白表达水平升高(P<0.05);与肝纤维化模型组比较,姜黄素给药组大鼠肝脏组织中Tgf-β1和α-Sma蛋白表达水平降低(P<0.05)。结论:姜黄素有治疗肝纤维化的作用,有望成为预防和治疗胆汁淤积性肝纤维化的药物。Objective To investigate the protective effects of curcumin on the hepatic injury of the rats with experimental hepatic fibrosis,and to clarify its mechanism.Methods The hepatic fibrosis models of rats were established by bile duct ligation.21 rats were randomly divided into sham operation group(given saline),model group(given saline for model rats),curcumin group(given 400mg·kg-1 curcumin for model rats);there were7 rats in each group.The activities of aspartate aminotransferase(AST),alanine aminotransferase(ALT)and the level of total bilirubin(Tbil)in serum of the rats in various groups were detected after treated for 2 weeks;the pathomorphology of liver tissue was observed by hematoxylin and eosin(HE)staining;the deposition of collagen in the liver tissue was observed by Massion staining;the expression levels of transforming growth factor-beta1(Tgf-β1)andα-smooth muscle actin(α-Sma)proteins were detected by Western blotting method.Results Compared with sham operation group,the activities of AST,ALT and the levels of Tbil in serum of the rats in model group and curcumin group were increased(P〈0.05).Compared with model group,the activities of AST,ALT and the level of Tbil were increased in curcumin group were decreased(P〈0.05).The liver tissue of the rats in model group was obviously damaged with inflammatory cell infiltration,collagen deposition and bile duct proliferation;the pathological changes of liver tissue were significantly improved after curcumin treatment.The Western blotting results showed that the levels of Tgf-β1andα-Sma proteins in the liver tissue of the rats in model group were increased compared with sham opration group(P〈0.05);compared with model group,the levels of Tgf-β1andα-Sma proteins in the liver tissue of the rats in curcumin group were decreased(P〈0.05).Conclusion Curcumin shows the therapeutical effects on hepatic fibrosis,which is expected to be the drug to prevent and cure cholestatic hepatic fibrosis.
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