N-乙酰半胱氨酸对非酒精性脂肪性肝炎模型小鼠肝细胞线粒体自噬的影响  

Effect of N-acetylcysteine on mitophagy of hepatocytes in mice with nonalcoholic steatohepatitis

作　　者：张宁萍 方颖 刘雪静 谢黎 吴健 沈锡中 ZHANG Ning-ping;FANG Ying;XIE Li;WU Jian;SHEN Xi-zhong(Department of Gastroenterology and Hepatology,Zhongshan Hospital of Fudan University,Shanghai 20032,China;Shanghai Institute of Liver Diseases,Fudan University Shanghai Medical College,Shanghai 20032,China;Department of Medical Microbiology,Fudan University School of Basic Medical Sciences,Shanghai 200032,China)

机构地区：[1]复旦大学附属中山医院消化科上海市肝病研究所,上海200032 [2]复旦大学基础医学院病原生物系

出　　处：《肝脏》2020年第4期382-386,共5页Chinese Hepatology

基　　金：北京医卫健康公益基金会(YWJKJJHKYJJ-G17014)。

摘　　要：目的在非酒精性脂肪性肝炎模型小鼠中探索N-乙酰半胱氨酸(NAC)对肝细胞线粒体自噬的影响。方法C57BL/J6小鼠分别给予16周的正常饮食、高脂高糖(HFCD)饮食和HFCD+NAC饮食。比较HE和Masson染色、ALT、AST、IL-1β、肝组织甘油三酯水平评价小鼠肝损伤。通过免疫荧光染色观察线粒体自噬。比较3组小鼠肝组织内线粒体自噬标志物在mRNA和蛋白水平的变化。结果HFCD组小鼠较对照组ALT[(24.9±2.12)比(176.7±44.32)U/L,P<0.05]、AST[(76.7±9.06)比(291.3±39.66)U/L,P<0.05]、IL-1β[(2.94±0.08)比(9.12±1.21),P<0.05]显著升高,HFCD+NAC组较HFCD组肝功能好转,IL-1β降低[(9.12±1.21)比(6.77±0.58)ng/L,P<0.05]。HFCD组小鼠肝组织内Parkin、PINK1表达降低,同时LC3B II/I比值降低,P62表达量增高。提示HFCD组小鼠肝细胞线粒体自噬水平降低。HFCD+NAC组较HFCD组线粒体自噬水平升高,差异有统计学意义(P<0.05)。结论NAC可能通过改善肝细胞线粒体自噬,进而减轻肝细胞炎症进展。Objective To investigate the effect of N-acetylcysteine(NAC)on mitophagy in mice with nonalcoholic steatohepatitis.Methods C57BL/J6 mice were fed with control diet,high-fat and high-calories(HFCD)diet and a HFCD+NAC diet for 16 weeks.HE and Masson staining were used to evaluate liver injury.Liver function,IL-1β,blood glucose and triglyceride levels in liver tissues were detected.Immunofluorescence staining of frozen section of liver tissue was used to observe mitophagy.Changes of mRNA and protein levels of mitophagy markers in liver tissues of 3 groups of mice were compared.Results Compared to control group,the ALT[(24.9±2.12)vs(176.7±44.32)U/L,P<0.05],AST[(76.7±9.06)vs(291.3±39.66)U/L,P<0.05]and IL-1β[(2.94±0.08)vs(9.12±1.21),P<0.05]levels of HFCD group were increased.The liver function of HFCD+NAC group was improved,and the IL-1βlevels were decreased[(9.12±1.21)vs(6.77±0.58)ng/L,P<0.05].The expression of Parkin,PINK1 and LC3B II/I ratio in the liver tissues of HFCD group decreased,while the P62 level was increased.These results suggested that the level of mitophagy in HFCD group was decreased.Compared with the HFCD group,mitophagy of hepatocytes in the HFCD+NAC group improved(P<0.05).Conclusion NAC may reduce hepatocyte inflammatory progression by improving mitophagy of hepatocytes in mice with nonalcoholic steatohepatitis.

关 键 词：N-乙酰半胱氨酸 非酒精性脂肪性肝炎 线粒体自噬 

分 类 号：R28[医药卫生—中药学]