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目的 本研究旨在探讨虎杖苷(PD)对高脂饮食诱导的非酒精性脂肪性肝病(NAFLD)小鼠模型及人肝癌细胞系G2(HepG2)细胞模型的影响，揭示其潜在分子机制。方法 30只6周龄雄性SPF级C57BL/6J小鼠，随机分为正常饮食组和高脂饮食组，后者建立NAFLD小鼠模型后进一步分为高脂饮食(HFD)组和虎杖苷治疗(PD)组。PD组灌胃给药PD 250 mg/(kg·d),为期10周，期间监测体质量并进行口服葡萄糖和胰岛素耐量测试。实验结束时，通过一系列实验评估PD对小鼠肝重、血脂、肝脏脂质积累及肝损伤标志物的影响。通过qRT-PCR和Western blot法检测G0/G1开关基因2(G0S2)和脂肪三酰甘油脂肪酶(ATGL)的表达，并通过免疫组织化学染色再次验证基因表达。细胞计数试剂盒-8(CCK-8)法评估PD对HepG2细胞活性的影响，油红O染色观察脂质积累，通过qRT-PCR和Western blot法检测G0S2和ATGL的表达，并验证了G0S2被敲低后脂质积累和基因表达的改变。结果 PD降低小鼠体质量、肝重及血清和肝组织中的天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、三酰甘油(TG)和总胆固醇(TC)水平(P<0.05),减轻肝组织病理损伤，降低G0S2表达(P<0.05),增加ATGL表达(P<0.05)。在细胞层面，PD减少脂滴累积，改善脂质代谢，降低G0S2表达(P<0.05),增加ATGL表达(P<0.05)。即使在G0S2被敲低的细胞中，PD仍能促进脂肪分解(P<0.01)。结论 PD通过调节G0S2和ATGL表达促进肝脂肪分解，减轻高脂饮食诱导的小鼠NAFLD模型的代谢紊乱和肝脏损伤，为NAFLD治疗提供新策略。
Abstract：Objective To investigate the effects of polydatin on a high-fat diet-induced non-alcoholic fatty liver disease(NAFLD) mouse model and hepatoma G2(HepG2) cell model, and to reveal its potential molecular mechanisms. Methods Thirty 6-week-old male SPF C57BL/6J mice were randomly divided into a normal diet group and a high-fat diet group. After the NAFLD mouse model was established in the high-fat diet group, they were further divided into a model group and a polydatin treatment group. The polydatin treatment group was administered polydatin by gavage at a dose of 250 mg/(kg·d) for 10 weeks, during which body weight was monitored and oral glucose and insulin tolerance tests were performed. At the end of the experiment, a series of tests to evaluate the effects of polydatin on mouse liver weight, blood lipids, liver lipid accumulation, and liver injury markers were performed. The expression of G0/G1 switch gene 2(G0S2) and adipose triglyceride lipase(ATGL) was measured by qRT-PCR and Western blot, and gene expression was further verified using immunohistochemical staining. The effects of polydatin on HepG2 cell activity was assessed by CCK-8 assay, lipid accumulation was observed by oil red O staining, and the expression of G0S2 and ATGL was detected by qRT-PCR and Western blot. Results Polydatin significantly reduced the body weight, liver weight, and serum and liver tissue levels of aspartate aminotransferase(AST), alanine aminotransferase(ALT), triglyceride(TG), and total cholesterol(TC) in mice(P<0.05), alleviated pathological liver damage, decreased G0S2 expression(P<0.05), and increased ATGL expression(P<0.05). At the cellular level, polydatin reduced lipid droplet accumulation, improved lipid metabolism, decreased G0S2 expression(P<0.05), and increased ATGL expression(P<0.05). Even in cells with knockdown of G0S2, polydatin still promoted fat decomposition(P<0.01). Conclusion Polydatin promotes hepatic fat breakdown by regulating the expression of G0S2 and ATGL, helping to alleviate metabolic disorders and liver damage in the NAFLD mouse model caused by a high-fat diet, offering a new strategy for treating NAFLD.
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基本信息:
DOI：10.19405/j.cnki.issn1000-1492.2025.10.010
中图分类号:R285.5
引用信息:
[1]盛鲁光,刘丹丹,刘维斌,等.虎杖苷通过调节G0S2和ATGL表达改善非酒精性脂肪肝病的研究[J].安徽医科大学学报,2025,60(10):1847-1856.DOI:10.19405/j.cnki.issn1000-1492.2025.10.010.
基金信息:
国家自然科学基金项目(编号：82074381); 上海市卫生健康委员会科研项目(编号：202240309); 上海市普陀区卫生健康系统科技创新项目(编号：ptkwws201911); 上海市普陀区卫生健康系统临床特色专科建设计划项目(编号：2020tszk01)~~