[关键词]
[摘要]
本文研究了表没食子儿茶素没食子酸酯(EGCG)对小鼠非酒精性脂肪性肝病(NAFLD)的干预作用。应用高脂饲料喂养ApoE-/-小鼠建立NAFLD小鼠模型,研究EGCG对NAFLD小鼠血液和肝组织中糖脂代谢、脂肪酸氧化、氧化应激水平、肝组织结构以及AMPK/SIRT1/SREBP-1c/PPARγ信号通路相关基因表达的影响。结果表明EGCG治疗后肝组织病理学变化明显改善,小鼠体质量、肝质量、肝质量指数较模型组显著降低至110.98%、115.01%,115.64%、136.48%和104.20%、118.70%(p<0.01);血液和肝组织中糖脂代谢、脂肪酸氧化、氧化应激水平改善幅度在11.85%~86.06%之间,与模型组比较具有显著性差异(p<0.05或p<0.01);升高肝组织中AMPKα、SIRT1 mRNA及p-AMPKα、SIRT1蛋白表达幅度在13.21%~75.82%之间,降低肝组织FASN、ACC-1、SREBP-1c、SCD-1、PPARγ mRNA和FASN、p-ACC-1、p-SREBP-1c、SCD-1、PPARγ蛋白表达幅度在19.59%~92.07%之间,改善p-AMPKα/AMPKα、p-ACC-1/ACC-1和p-SREBP-1c/SREBP-1c比率在39.20%~93.07%之间,与模型组比较具有显著性差异(p<0.05或p<0.01)。本研究表明EGCG可通过调控AMPK/SIRT1/SREBP-1c/PPARγ信号通路相关基因的表达来改善NAFLD小鼠糖脂代谢、脂肪酸氧化和氧化应激状态。
[Key word]
[Abstract]
The protective effects of epigallocatechin gallate (EGCG) on nonalcoholic fatty liver disease (NAFLD) in mice were investigated. The NAFLD ApoE-/- mice model was established by feeding high fat food. Then, the effects of EGCG on glucose and lipid metabolism, fatty acid oxidation, oxidative stress level, liver tissue structure and the gene expressions of AMPK/SIRT1/SREBP-1c/PPARγ signaling pathway in NAFLD mice were analyzed. The results indicated that after EGCG treatment, the pathological changes of liver tissue were evidently ameliorated; compared with the model group, the body weight, liver mass and liver mass index of mice were significantly reduced to 110.98%, 115.01%, 115.64%, 136.48% and 104.20%, 118.70% respectively (p<0.01, respectively). The levels of glucose and lipid metabolism, fatty acid oxidation and oxidative stress in blood and liver tissues were markedly improved by 11.85%~86.06% compared with model group (p<0.05 or p<0.01, respectively). Further study indicated that the AMPKα, SIRT1 mRNA and p-AMPKα, SIRT1 protein expressions in liver tissue were obviously elevated by 13.21%~75.82%. In contrast, the FASN、ACC-1、SREBP-1c、SCD-1、PPARγ mRNA and FASN、p-ACC-1、p-SREBP-1c、SCD-1、PPARγ protein expressions in liver tissue were dramatically reduced by 19.59%~92.07%, the p-AMPKα/AMPKα、p-ACC-1/ACC-1 and p-SREBP-1c/SREBP-1c ratios significantly ameliorated by 39.20%~93.07% compared with model group (p<0.05 or p<0.01, respectively). The results demonstrated that EGCG could ameliorate glucose and lipid metabolism, fatty acid oxidation and oxidative stress in NAFLD mice by regulating there lated gene expressions of AMPK/SIRT1/SREBP-1c/PPARγ signaling pathway.
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[基金项目]
宜昌市科学技术局资助项目(A18-302-a2);三峡大学硕士学位论文培优基金资助项目(2020SSPY114;2019SSPY159)