维生素E对非酒精性脂肪性肝病小鼠肝脏SIRT1、PGC-1α表达的影响

发布时间：2018-05-15 23:17

本文选题：非酒精性脂肪性肝病 + 沉默信息调节蛋白　；参考：《中国药学杂志》2017年12期

【摘要】：目的观察维生素E(Vit E)对非酒精性脂肪性肝病(NAFLD)小鼠肝脏SIRT1和PGC-1α表达的影响,探讨Vit E在NAFLD小鼠中抗氧化应激的作用机制。方法采用高脂饮食24周建立C57BL/6小鼠NAFLD模型,于造模第7周起以50 mg·kg~(-1)·d~(-1)Vit E灌胃干预18周,HE和Masson染色观察肝组织病理学变化;生化法检测血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)水平,黄嘌呤氧化酶法检测肝脏总超氧化物歧化酶(SOD)、MnSOD水平,硫代巴比妥酸法检测肝脏丙二醛(MDA)含量;Real-time PCR和免疫组化法检测肝组织沉默信息调节蛋白1(SIRT1)、过氧化物酶体增殖物激活受体γ辅激活因子1α(PGC-1α)mRNA和蛋白的表达。结果长期高脂饮食可诱导小鼠肝组织脂肪变、炎症及纤维化,形成NAFLD,NAFLD模型组小鼠血清ALT、AST水平较正常组显著增高(P0.05),肝组织SIRT、PGC-1α基因mRNA和蛋白表达均较正常组明显减少(P0.01);肝组织总SOD、MnSOD水平较正常组明显降低(P0.01),MDA含量较正常组明显增多(P0.05);应用Vit E干预后能一定程度减轻肝组织炎症程度和纤维化程度;Vit E组小鼠血清ALT、AST水平较模型组显著下降(P0.01、P0.05),肝组织SIRT1、PGC-1α基因mRNA和蛋白表达均较模型组显著增强(P0.05),肝组织总SOD和MnSOD水平也较模型组明显增高(P0.05),MDA含量则较模型组明显下降(P0.05)。结论 Vit E通过调节SIRT1/PGC-1α信号通路关键因子的表达,纠正高脂饮食诱导的NAFLD小鼠氧化与抗氧化体系的失衡,减轻肝脏炎症损伤,防止NAFLD的进展。
[Abstract]:Objective to observe the effect of Vitamin E on the expression of SIRT1 and PGC-1 伪 in liver of non-alcoholic fatty liver disease (NAF LDD) mice, and to explore the mechanism of Vit E in anti-oxidative stress in NAFLD mice. Methods the NAFLD model of 24 Zhou Jianli C57BL/6 mice with high fat diet was used to observe the histopathological changes of liver tissue by intragastric administration of 50 mg / kg d~(-1)Vit E for 18 weeks from the 7th week to observe the pathological changes of liver tissue by HE and Masson staining. Serum alanine aminotransferase (alt), aspartate aminotransferase (AST) and total superoxide dismutase (SOD) in liver were detected by biochemical method and xanthine oxidase method. The content of malondialdehyde (MDA) in liver was detected by thiobarbituric acid method and real-time PCR was detected by immunohistochemistry. The mRNA and protein expression of hepatic silence information regulatory protein (1SIRT1) and peroxisome proliferator activated receptor 纬 coactivator 1 伪 (PGC-1 伪) were detected. Results Long-term high-fat diet could induce fatty degeneration, inflammation and fibrosis in liver tissue of mice. Compared with the normal group, the serum alt level of the NAFLD- NAFLD model group was significantly higher than that of the normal group (P 0.05), the expression of mRNA and protein of SIRTP PGC-1 伪 gene in liver tissue was significantly lower than that of the normal group, and the total SOD level of liver tissue was significantly lower than that of the normal group, and the content of MDA in the liver tissue was significantly lower than that in the normal group. After intervention of Vit E, the level of alt in serum of mice in Vit E group was significantly lower than that in the model group, and the expression of mRNA and protein of PGC-1 伪 gene in liver tissue was significantly higher than that in the model group, and the expression of P0.05 in liver tissue was significantly higher than that in the model group. Compared with the model group, the total SOD and MnSOD levels of the model group were significantly higher than that of the model group. Conclusion Vit E can correct the imbalance of oxidation and antioxidant system in NAFLD mice induced by high fat diet by regulating the expression of key factors in SIRT1/PGC-1 伪 signaling pathway, alleviate the liver inflammation and prevent the progress of NAFLD.
【作者单位】：金华市中心医院浙江大学金华医院;浙江省中医院浙江中医药大学第一临床医学院;
【基金】：浙江省中医药科学研究基金(2013ZA047) 浙江省自然科学基金资助项目(LY13H290011)
【分类号】：R965

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