姜黄素激活自噬对非酒精性脂肪性肝病大鼠线粒体途径凋亡的影响  

Curcumin ameliorates mitochondrial apoptosis by inducing autophagy in non-alcoholic fatty liver disease rats

作　　者：吴鹏波[1] 宋琪 俞媛洁[1] 饶倩 张国 柴红[1] 谭诗云[1] WU Pengbo;SONG Qi;YU Yuanjie;RAO Qian;ZHANG Guo;CHAI Hong;TAN Shiyun(Department of Gastroenterology,Renmin Hospital of Wuhan University,Hubei Key Laboratory of Digestive Diseases,Wuhan 430060;Department of Gastroenterology,Guangxi District People’s Hospital,China)

机构地区：[1]武汉大学人民医院消化内科消化系统疾病湖北省重点实验室,湖北武汉430060 [2]广西区人民医院消化内科

出　　处：《胃肠病学和肝病学杂志》2020年第8期861-864,共4页Chinese Journal of Gastroenterology and Hepatology

基　　金：中央部属高校青年教师资助项目(2042017kf0099);湖北省自然科学基金(2018CFB236);湖北省卫生和计划生育委员会面上项目(WJ2017M019);武汉大学人民医院引导基金(RMYD2018M29)。

摘　　要：目的探讨姜黄素对非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)大鼠的治疗作用及机制。方法油红O染色观察各组大鼠肝内细胞脂滴分布,透射电镜观察肝组织中自噬泡形成情况。蛋白印迹检测P62、微管相关蛋白1轻链3-Ⅱ(LC3-Ⅱ)、自噬相关蛋白(Beclin-1)和B淋巴细胞瘤-2(Bcl-2)、相关x蛋白(Bax)、线粒体内细胞色素C(mCytc)、半胱氨酸蛋白酶(Caspase-3、Caspase-9)标记蛋白的表达水平。结果与正常对照组比较,肝组织脂质沉积在模型组中明显增加;姜黄素明显抑制模型组大鼠肝组织脂质沉积,自噬抑制剂削弱姜黄素的治疗作用;透射电镜观察发现正常对照组可见散在自噬泡,模型组自噬泡数量显著减少,姜黄素可明显增加自噬体数量。蛋白印迹结果提示,模型组大鼠肝组织中Bax、Caspase-3、Caspase-9、P62蛋白表达均升高,而mCytc、Bcl-2、Beclin-1、LC3Ⅱ/LC3Ⅰ均降低;经姜黄素治疗后肝组织中Bax、P62、Caspase-3、Caspase-9蛋白表达均降低,而mCytc、Bcl-2、Beclin-1、LC3Ⅱ/LC3Ⅰ升高;自噬抑制剂可以部分抑制姜黄素对自噬和凋亡相关蛋白的影响。结论姜黄素对NAFLD大鼠模型的抗凋亡作用与诱导自噬有关。Objective To investigate the role of curcumin on experimental non-alcoholic fatty liver disease(NAFLD) rats and its underlying mechanism. Methods Oil red O staining was performed to characterize hepatic steatosis. The autophagic bodies in liver tissues were observed by transmission electron microscopy. Western blotting was applied to determin the expression level of targetted protein. Results Compared with control group, reduced autophagosome was easily found in model group, while curcumin significantly increased the number of autophagosome, which was inhabited by 3-MA. Increased Bax, P62, Caspase-3, Caspase-9 protein expressions and decreased mCytc, Bcl-2, Beclin-1, LC3Ⅱ/LC3Ⅰ expressions were found in model group. Bax, P62, Caspase-3, Caspase-9 protein expressions decreased while the mCytc, Bcl-2, Beclin-1, LC3Ⅱ/LC3Ⅰ expressions dramatically increased after treatment with curcumin, which was partially inhabited by 3-MA. Conclusion Curcumin ameliorates hepatic steatosis by effectively inhibited mitochondrial apoptosis by enhancing autophagy.

关 键 词：姜黄素 非酒精性脂肪性肝病 自噬 细胞凋亡 

分 类 号：R575.5[医药卫生—消化系统]