首页|肝细胞DEP结构域蛋白5/哺乳动物雷帕霉素靶蛋白复合物1信号轴在非酒精性脂肪肝形成中的作用

肝细胞DEP结构域蛋白5/哺乳动物雷帕霉素靶蛋白复合物1信号轴在非酒精性脂肪肝形成中的作用

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目的 建立肝细胞Dishevelled/Egl-10/pleckstrin(DEP)结构域蛋白 5(DEPDC5)基因(Depdc5)肝细胞特异性敲除小鼠高脂喂养模型，探讨DEPDC5/哺乳动物雷帕霉素靶蛋白复合物 1(mTORC1)信号轴对非酒精性脂肪肝的调控。方法 构建肝细胞特异性敲除Depdc5flox/flox 模型;Alb-Cre小鼠(LKO)，Depdc5flox/flox 小鼠(Loxp)作为对照。32只2～3月龄雄性小鼠随机分为高脂LKO组、高脂Loxp对照组、高脂+雷帕霉素LKO组及高脂+雷帕霉素Loxp对照组，每组8只。检测肝脏血清生物化学指标、脂质含量、蛋白、mRNA及病理切片，采用 GraphPad Prism 8 软件进行统计学分析。结果 高脂喂养导致LoxP小鼠肝脏脂肪变性，LKO小鼠肝脏脂肪变性减轻但合并出现肝损伤;雷帕霉素抑制了Depdc5敲除引起的mTORC1通路激活，显著改善Loxp小鼠肝脏脂肪变性，并改善LKO小鼠的肝损伤。结论 Depdc5基因敲除能够保护高脂喂养小鼠肝脏脂肪变性，雷帕霉素可以改善DEPDC5缺失诱发的肝损伤。
Roles of hepatic Dishevelled/Egl-10/pleckstrin domain-containing protein 5/mammalian target of rapamycin complex 1 signaling axis on the development of non-alcoholic fatty liver disease
Objective To investigate the effect of hepatic Dishevelled/Egl-10/pleckstrin domain-containing protein 5(DEPDC5)/mammalian target of rapamycin complex 1(mTORC1)on nonalcoholic fatty liver disease by establishing a high-fat diet feeding model of Depdc5 gene hepatocyte specific knockout mice.Methods Depdc5flox/flox mice were constructed and mated with Alumin-Cre mice to obtain Depdc5flox/flox;Alb-Cre mice(LKO),Depdc5flox/flox mice were as control(Loxp).Totally 32 male mice aged 2-3 months were randomly divided into high-fat-diet LKO group,high-fat-diet Loxp control group,high-fat-diet+rapamycin LKO group,and high-fat-diet+rapamycin Loxp control group,with 8 mice in each group.Liver serum biochemistry,lipid content,protein,mRNA and pathological sections were detected;Graphpad prism 8 software was used for statistical analysis.Results High-fat-diet induced liver steatosis in Loxp mice,while LKO mice were protected from steatosis but had aggravated liver injury.Rapamycin treatment attenuated the hyperactivation of mTORC1 pathway caused by Depdc5 knockout,alleviated the liver steatosis in Loxp mice and liver injury in LKO mice.Conclusion Deletion of Depdc5 gene protects mice from high-fat-diet induced liver steatosis and rapamycin treatment might be used to improve liver injury caused by DEPDC5 loss of function.

Dishevelled/Egl-10/pleckstrin containing protein 5Mammalian target of rapamycin complex 1High-fat-dietRapamycinNonalcoholic fatty liverWestern blottingMouse

徐琳、熊熙文、李遵、黄蓉、麻红辉、马洁

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新乡医学院医学技术学院,河南 新乡 453003

新乡医学院新乡市代谢与整合生理学重点实验室,河南 新乡 453003

新乡医学院基础医学院,河南 新乡 453003

新乡医学院法医学院,河南 新乡 453003

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Dishevelled/Egl-10/pleckstrin结构域蛋白5 哺乳动物雷帕霉素靶蛋白 高脂饮食 雷帕霉素 非酒精性脂肪肝 免疫印迹法 小鼠

河南省高等学校重点科研项目

23A310005

2024

10.16098/j.issn.0529-1356.2024.03.006

解剖学报
中国解剖学会

解剖学报

CSTPCD
影响因子：0.462
ISSN：0529-1356
年,卷(期)：2024.55(3)
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