白芍总苷对非酒精性脂肪性肝病大鼠HMGB1、RAGE通路的调控作用  

Effect of total glucosides of paeony regulate HMGB1,RAGE pathway on nonalcoholic fatty liver disease in rats

作　　者：杨以琳[1] 郑琳颖[1] 古伟明[1] 潘竞锵 武昕[3] 黎耀俊[3] YANG Yilin ZHENG Linying GU Weiming PAN Jingqlang WU Xin LI Yaojun(Guangzhou Hospital of Traditional Chinese Medicine, Guangzhou 510130, Guangdong , China Department of Pharmacology, Guangzhou Institute of Traditional Chinese Medicine ＆ Materia Medica, Guangzhou 510130, Guangdong , China Guangdong Medical Lab Animal Center, Guangzhou 528248, Guangdong , China)

机构地区：[1]广东省广州市中医医院,广东广州510130 [2]广东省广州市中医中药研究所药理研究室,广东广州510130 [3]广东省医学实验动物中心,广东广州528248

出　　处：《中国临床药理学与治疗学》2017年第6期611-616,共6页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：2013年广东省科学技术厅科技计划项目(第二批-18);广州市卫生局中医药中西医结合科技项目(20142A011003)

摘　　要：目的:观察白芍总苷(TGP)对非酒精性脂肪性肝病(NAFLD)大鼠高迁移率族蛋白1(HMGB1)、晚期糖基化终产物受体(RAGE)通路的调控作用。方法:用高脂-高果糖餐诱导NAFLD大鼠模型,将模型大鼠随机分为模型组,TGP高、低剂量组(200、100 mg·kg^(-1)·d^(-1)),二甲双胍组(200 mg·kg^(-1)·d^(-1)),水飞蓟宾组(200 mg·kg^(-1)·d^(-1)),并另设正常对照组。用药6周后观察各组大鼠胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、甘油三酯(TG)、游离脂肪酸(FFA)、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、空腹血糖(FBG)、餐后2 h血糖(2 h BG)、胰岛素(Fins)水平,计算胰岛素抵抗指数(HOMA-IR)和肝脏指数。Western blot方法检测肝组织中HMGB1、RAGE蛋白活性。结果:与模型组比较,TGP高、低剂量组LDL-C、TG、TC、FFA、ALT、AST、2 h BG、Fins、HOMA-IR均明显降低(P<0.01或P<0.05),高、低剂量TGP在拮抗胰岛素抵抗、降糖降脂、改善肝功能方面有较显著的作用,TGP高、低剂量组均可下调HMGB1(P<0.01)和RAGE(P<0.05)蛋白的表达。结论:TGP通过抑制HMGB1、RAGE信号通路的转导而起到改善NAFLD大鼠的糖脂代谢异常,拮抗胰岛素抵抗,改善肝功能的作用。AIM： To observe the regulatory effect of total glucosides of paeony（ TGP） on the HMGB1 and RAGE pathway（ NAFLD） in rats with nonalcoholic fatty liver disease. METHODS： High fat and high fructose diet were administered to induce NAFLD rat models. The model rats were randomly divided into NAFLD group,TGP high（ 200mg·kg^（-1）·d^（-1）） and low dose group（100 mg·kg^（-1）·d^（-1））,Metformin group（200 mg·kg^（-1）·d^（-1））,Silybin group（ 200 mg · kg^（-1）· d^（-1））,and another blank control group was established. the rats total Cholesterol（ TC）,low density lipoprotein cholesterol（ LDL-C）,high density lipoprotein cholesterol（HDL-C） and triglyceride（ TG）,free fatty acid（FFA）,alanine aminotransferase（ALT）,aspartate amino shifting enzyme（ AST）,fasting blood glucose（ FBG）,postprandial 2 hours blood glucose（ 2h BG）,insulin（ fins） were observed 6 weeks after medication,and the insulin resistance index（ HOMA-IR） and liver index were thence calculated.Western blot was applied to detect the high mobility group protein 1（ HMGB1） and the receptor of advanced glycation end products（ RAGE） protein inliver tissue. RESULTS： Compared with model group,the contents of 2 h BG,fins,HOMA-IR,LDL-C,TC,TG,FFA,ALT,AST,GST were decreased in high and low dose TGP groups（ P 0. 05 or P 0. 01）. High and low dose of TGP groups presented fair effect in antagonizing insulin resistance,lowering lipid and blood glucose as well as improving liver function. Also,TGP high and low dose group can down-regulate the expressions of HMGB1（ P 0. 01） and RAGE（ P 0. 05） proteins. CONCLUSION： TGP can improve the metabolism of glucose and lipid,antagonize the insulin resistance,enhance the insulin sensitivity and improve the role of liver function in NAFLD rats through inhibition of HMGB1,RAGE signaling pathway.

关 键 词：白芍总苷 非酒精性脂肪性肝病 信号通路 高迁移率族蛋白1 晚期糖基化终产物受体 

分 类 号：R965.2[医药卫生—药理学]