端粒酶RNA基因Terc在非酒精性脂肪性肝病中的作用机制研究
发布时间：2019-06-19 23:31
【摘要】：目的：非酒精性脂肪性肝病(NAFLD)是临床常见的慢性肝病,其发病机制尚未完全明确。研究发现,衰老与NAFLD的发生与发展密切相关,而端粒酶RNA基因Terc在衰老发生中起到重要的作用。然而,Terc是否参与NAFLD的发生发展及其确切分子机制尚未报道。本研究旨在通过体内实验的方法,探讨端粒酶RNA基因Terc在NAFLD的发生发展中可能的作用机制。方法：本研究采用蛋氨酸-胆碱缺乏(MCD)饮食饲养第二代端粒酶基因敲除小鼠(G2Terc-/-)与正常小鼠,在此基础上,采用苏木素-伊红(HE)染色,肝组织甘油三酯含量测定及荧光定量PCR等分子生物学手段,探讨端粒酶RNA基因Terc在NAFLD发生发展中的作用及分子机制。结果：(1)用MCD饮食成功构建NAFLD动物模型(2)第二代端粒酶基因敲除小鼠(G2 Terc-/-)显著增加MCD饮食诱导的肝组织脂肪沉积；而且G2 Terc-/-小鼠组肝脏甘油三酯含量高于野生型(WT)小鼠组(172.5μg/mg比150μg/mg) (P=0.018)(3)第二代端粒酶基因敲除小鼠(G2Terc-/-)组的脂质合成基因脂肪酸合成酶(FAS)表达高于野生型(WT)小鼠组(P=0.026),导致脂质合成增加(4)第二代端粒酶基因敲除小鼠(G2 Terc-/-)组的脂肪酸p氧化基因过氧化物酶体增殖物激活受体α表达低于野生型小鼠(WT)组(P=0.050),导致脂肪酸p氧化受损。结论：(1) Terc参与NAFLD的发生发展；(2) Terc基因缺失可能通过上调FAS基因及下调PPARa基因表达参与NAFLD发生和发展。
[Abstract]:Objective: non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease in clinic, and its pathogenesis is not completely clear. It was found that aging was closely related to the occurrence and development of NAFLD, and telomerase RNA gene Terc played an important role in senescence. However, it has not been reported whether Terc is involved in the occurrence and development of NAFLD and its exact molecular mechanism. The purpose of this study was to explore the possible mechanism of telomerase RNA gene Terc in the occurrence and development of NAFLD by means of in vivo experiments. Methods: the second generation telomerase gene knockout mice and normal mice were fed with methionine choline deficient (MCD) diet. On this basis, the role and molecular mechanism of telomerase RNA gene Terc in the occurrence and development of NAFLD were investigated by hematoxylin-eosin (HE) staining, determination of TG content in liver tissue and fluorescence quantitative PCR. Results: (1) the animal model of NAFLD was successfully constructed by MCD diet. (2) the second generation telomerase gene knockout mice (G2 Terc-/-) significantly increased the fat deposition of liver tissue induced by MCD diet. The content of TG in liver of G2Tercg mice was higher than that of wild type (WT) mice (172.5 渭 g / mg vs 150 渭 g / mg) (P 鈮，
本文编号：2502721
[Abstract]:Objective: non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease in clinic, and its pathogenesis is not completely clear. It was found that aging was closely related to the occurrence and development of NAFLD, and telomerase RNA gene Terc played an important role in senescence. However, it has not been reported whether Terc is involved in the occurrence and development of NAFLD and its exact molecular mechanism. The purpose of this study was to explore the possible mechanism of telomerase RNA gene Terc in the occurrence and development of NAFLD by means of in vivo experiments. Methods: the second generation telomerase gene knockout mice and normal mice were fed with methionine choline deficient (MCD) diet. On this basis, the role and molecular mechanism of telomerase RNA gene Terc in the occurrence and development of NAFLD were investigated by hematoxylin-eosin (HE) staining, determination of TG content in liver tissue and fluorescence quantitative PCR. Results: (1) the animal model of NAFLD was successfully constructed by MCD diet. (2) the second generation telomerase gene knockout mice (G2 Terc-/-) significantly increased the fat deposition of liver tissue induced by MCD diet. The content of TG in liver of G2Tercg mice was higher than that of wild type (WT) mice (172.5 渭 g / mg vs 150 渭 g / mg) (P 鈮，
本文编号：2502721
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