摘要
目的观察白芍总苷对果糖-高脂诱导非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)大鼠肝脏组织胞外信号调节激酶-1/2(p-ERK1/2)、Toll样受体-4(TLR4)和Toll样受体-9(TLR9)蛋白的表达。方法 SD大鼠随机分为正常对照组和果糖-高脂诱导造模组,后者连续10周果糖-高脂喂饲;第6周末建立疾病模型后,病鼠随机分为模型组、二甲双胍组(200mg·kg-1)、白芍总苷低剂量组(100 mg·kg-1)和高剂量组(200 mg·kg-1),每组均为10只。用药4周后处死所有实验大鼠,观察上述药物对血清空腹血糖(FBG),胰岛素含量(FIns),胰岛素敏感指数(ISI),胆固醇(TC),低密度脂蛋白-胆固醇(LDLC),高密度脂蛋白-胆固醇(HDL-C),三酰甘油(TG),游离脂肪酸(FFA)含量,检测丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、谷胱甘肽转移酶(GST)活性和肝脏指数(liver index),以及采用蛋白质印迹法检测肝脏组织p-ERK1/2、Toll样受体-4、TLR9蛋白表达。结果与正常大鼠比较,模型大鼠血糖、胰岛素、胆固醇、低密度脂蛋白-胆固醇、三酰甘油及游离脂肪酸含量、丙氨酸氨基转移酶、天冬氨酸氨基转移酶和谷胱甘肽转移酶的活性单位、肝脏指数、p-ERK1/2、Toll样受体-4和TLR9蛋白表达明显上调(P<0.01或P<0.05),胰岛素敏感指数水平及高密度脂蛋白-胆固醇含量明显降低(P<0.01),二甲双胍和白芍总苷低、高剂量组均能改善此现象(P<0.01或P<0.05),但对丙氨酸氨基转移酶的含量改变没有统计学差异(P>0.05)。结论白芍总苷能改善果糖-高脂诱导非酒精性脂肪性肝病大鼠糖脂代谢异常及拮抗胰岛素抵抗,增强胰岛素敏感性,改善肝功能;其作用机制与白芍总苷下调肝脏组织p-ERK1/2、Toll样受体-4、TLR9蛋白表达作用有关。
OBJECTIVE To investigate total glucosides paeony（ TGP） on the expression phosphorylated extracellelar signal regulated kinase 1 /2（ p-ERK1 /2）,Toll-like receptors 4（ TLR4） and Toll-like receptors 9（ TLR9） in rats with nonalcoholic fatty liver disease（ NAFLD） induced by fructose and high-fat feed. METHODS SD rats were divided into normal group and test groups. The rats in test groups were fed with fructose and high-fat feed for 10 weeks totally to induce the test model. After 6 weeks the model was established,the rats were divided into four groups randomly,the model group（ NAFLD）,the metformin group（ Met,200 mg·kg^-1）,the low-dose TGP group（ TGP-L,100 mg·kg^-1） and the high-dose TGP group（ TGP-H,200 mg·kg^-1）（ n = 10）. Four weeks later all the rats were killed and checked the indexes such as serum fasting blood glucose（ FBG）,fasting insulin（ FIns）,insulin sensitivity index（ ISI）,total cholesterol（ TC）,low-density lipoprotein（ LDL-C）,high-density lipoprotein（ HDL-C）,triglyceride（ TG）,free fatty acids（ FFA）,alanine aminotransferase（ ALT）,aspartate aminotransferase（ AST）,glutathione S-transferase（ GST） and liver index.The expression p-ERK1 /2,TLR4 and TLR9 were inspected by Western-blot. RESULTS Compared with the normal group,the rats in test groups were with the high levels serum FBG,insulin,TC,LDL-C,TG,FFA,ALT,AST,GST,liver index,p-ERK1 /2,TLR4 and TLR9（ P〈0. 01 or P〈0. 05）,when the levels ISI and HDL-C were low（ P〈0. 01）. The Met,low-dose TGP and highdose TGP worked on all the targets（ P〈0. 01 or P〈0. 05） except the changes ALT（ P〉0. 05）. CONCLUSION By downregulating the expression ERK1 /2,TLR4 and TRL9,TGP can improve abnormal glucose and lipid metabolism and insulin resistance,enhance insulin sensitivity and ameliorate liver function in rats with NAFLD induced by fructose and high-fat feed.
出处
《中国药学杂志》
CAS
CSCD
北大核心
2014年第24期2168-2172,共5页
Chinese Pharmaceutical Journal
基金
广州市科技计划项目(2010Y1-C491)
广州市中医药中西医结合科技项目(2009-A-10)
关键词
白芍总苷
果糖
非酒精性脂肪性肝病
胰岛素抵抗
二甲双胍
胞外信号调节激酶-1/2
TOLL样受体-4
TOLL样受体-9
total glucosides paeony（TGP）
fructose
nonalcoholic fatty liver disease（NAFLD）
insulin resistance（IR）
metformin（Met）
extracellular signal-regulated kinase-1 /2（ERK1 /2）
Toll-like receptors-4（TLR4）
Toll-like receptors-9（TLR9）
