摘要
目的观察表没食子儿茶素没食子酸酯(epigallocatechin gallate,EGCG)对高脂血症大鼠血脂、肝脂、胆固醇合成的作用,探讨SIRT-1/FoxO1通路的调节机制。方法建立高脂血症大鼠模型,同时给予EGCG,观察胆固醇合成,酶联免疫吸附测定(ELISA)检测血清甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、游离脂肪酸(FFA)含量;苏木素-伊红染色(HE染色)观察肝脏组织学变化;生化检测血清谷丙转氨酶(ALT)和谷草转氨酶(AST)变化;Western blot和qRTPCR检测SIRTI/FOXO1通路相关蛋白表达。结果 EGCG 50mg/kg能明显降低高脂血症大鼠肝重和肝系数,降低血清TG、TC、LDL-C和FFA水平(P<0.05),同时对血清HDL-C有一定的升高作用;EGCG可降低高脂血症引起的肝损伤,降低大鼠血清ALT和AST水平。模型组中SIRTI表达升高,FOXO1表达降低;EGCG可以激活SIRT1,促使FOXO1表达升高,其表达趋势与非诺贝特组一致。结论 EGCG可缓解高脂血症大鼠肝损伤,激活SIRT1,进而激活FoxO1蛋白,抑制肝脏胆固醇合成。
Objective To study the role of epigallocatechin gallate（EGCG） on blood lipids, liver lipids and cholesterol synthesis and SIRT-1/FoxO1 pathway in hyperlipidemic rats. Methods The rat models of hyperlipidemia were established and administered EGCG. Cholesterol synthesis was observed, ELISA was used to determine the contets of serum triglyceride（TG）, total cholesterol （TC）, low-density lipoprotein cholesterol（LDL-C）, high-density lipoprotein cholesterol（HDL-C） and free fatty acid（FFA）. HE staining was utilized to observe the histological change of liver. Biochemical method was applied to measure serum alanine aminotransferase （ALT） and aspartate transaminase （AST） changes. Western blot and qRT-PCR were employed to detect the expression of SIRT1/FOXO1 pathway-related proteins. Results EGCG 50 mg/kg obviously decreased the liver weight and liver coefficient, reduced serum TG, TC, LDL-C and FFA levels（P〈0.05）, and increased serum HDL-C levels in hyperlipidemic rats. EGCG diminished hyperlipidemia-induced liver injury, and reduced serum ALT and AST levels. In the model group, SIRT1 expression level increased, and FOXO1 expression level decreased. EGCG activated SIRT1 and increased FOXO1 expression, consistent with the fenofibrate group. Conclusion EGCG could alleviate liver injury, activate SIRT1 and FoxO1 protein, inhibit hepatic cholesterol synthesis in hyperlipidemic rats.
作者
蔡莹
李勇男
CAI Ying 1, LI Yong-nan 2(1. Department of Developmental Biology, Basic Medical College, Shenyang 110122, and 2. Department of General Surgery, Shengjing Hospital, China Medical University, Shenyang 110004, China)
出处
《解剖科学进展》
2018年第2期113-117,共5页
Progress of Anatomical Sciences
基金
国家自然科学基金(81200318)
