翻白草总黄酮对2型糖尿病db/db小鼠降血糖的作用机制  

Hypoglycemic Effect of Total Flavonoids from Potentillae Discoloris Herba in Type 2 Diabetic db/db Mice

作　　者：孔晓妮 崔海燕[2] 周洪雷[1] KONG Xiao-ni;CUI Hai-yan;ZHOU Hong-lei(School of Pharmacy,Shandong University of Traditional Chinese Medicine(TCM),Ji'nan 250355,China;Shandong College of TCM,Yantai 264199,China)

机构地区：[1]山东中医药大学药学院,济南250355 [2]山东中医药高等专科学校,山东烟台264199

出　　处：《中国实验方剂学杂志》2021年第3期78-84,共7页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：山东省高等学校科技计划项目(J18KA303);山东省中医药科技发展计划项目(2013-141)。

摘　　要：目的:探讨翻白草总黄酮对2型糖尿病db/db小鼠的血糖、血脂、氧化应激、组织病理及肝脏磷脂酰肌醇-3激酶(PI3K)/蛋白激酶B(Akt)信号通路的影响。方法:24只db/db小鼠随机分为模型组、盐酸二甲双胍组(0.2 g·kg^(-1)),翻白草总黄酮低、高剂量组(0.1,0.4 g·kg^(-1)),另取6只db/m小鼠作为正常组。药物干预4周后,检测血清中空腹血糖(FBG),糖化血清蛋白(GSP),总胆固醇(TC),甘油三酯(TG),高密度脂蛋白胆固醇(HDL-C),低密度脂蛋白胆固醇(LDL-C),空腹血胰岛素(FINS),丙二醛(MDA)和超氧化物歧化酶(SOD)水平,计算胰岛素抵抗指数(HOMA-IR),检测肝糖原含量;苏木素-伊红(HE)染色观察肝脏、胰腺组织病理学变化;采用蛋白免疫印迹法(Western bolt)分别检测肝脏组织中胰岛素受体β(IRβ),胰岛素受体底物-1(IRS-1),PI3K,磷酸化PI3K(p-PI3K),Akt,p-Akt,葡萄糖转运蛋白4(GLUT4)蛋白的表达。结果:与正常组比较,模型组肝细胞排列紊乱,胞浆内可见大量脂肪空泡、脂滴,伴有部分细胞坏死。胰腺胰岛体积减小,胰岛组织和腺泡细胞界限不明显,细胞排列紊乱,部分细胞空泡化;血清FBG,GSP,TC,TG,LDL-C,FINS,MDA水平显著升高(P<0.01),血清HDL-C,SOD水平明显降低(P<0.05),肝糖原含量显著降低(P<0.01),肝脏组织IRβ,IRS-1,p-PI3K/PI3K,p-Akt/Akt和GLUT4蛋白表达显著降低(P<0.01)。与模型组比较,翻白草总黄酮低、高剂量组肝细胞形态结构较完整,空泡样变、水肿坏死显著减少。胰腺结构清晰,被膜结构完整,胰岛分布正常,结构完整。血清FBG,GSP,TC,TG,FINS,MDA水平明显降低(P<0.05),血清HDL-C,SOD水平明显升高(P<0.05),肝糖原含量显著升高(P<0.01),肝脏组织IRS-1,p-PI3K/PI3K,p-Akt/Akt和GLUT4蛋白表达明显升高(P<0.05)。结论:翻白草总黄酮可显著改善糖脂代谢紊乱及胰岛素抵抗,抗氧化应激,减轻肝脏、胰腺的病理损伤,提高肝脏组织PI3K/Akt信号通路中的相关蛋白表达,从而防治2型糖�Objective:The hypoglycemic effects and mechanisms of total flavonoids from Potentillae Discoloris Herba(TFE)on insulin resistance through the phosphatidylinositol-3 kinase(PI3 K)/protein kinase B(Akt)signaling pathway in db/db mice were investigated. Method:The 24 db/db mice were randomly divided into four groups,model group,metformin group and TFE 100,400 mg·kg^(-1) group respectively. The 6 db/m mice as normal control group. After 4 weeks treatment,the mice were processed and the levels of fasting blood glucose(FBG),glycated serum protein(GSP),fasting blood insulin(FINS),triglyceride(TG),total cholesterol(TC),low density lipoprotein cholesterol(LDL-C),high density lipoprotein cholesterol(HDL-C)in serum were detected. Homeostatic model assessments of insulin resistance(HOMA-IR)were quantified. Hematoxylin-eosin(HE)staining of liver and pancreatic tissues were examined. The expression of IRβ, IRS-1,PI3 K,phosphorylation-PI3 K(p-PI3 K),Akt,phosphorylation-Akt(p-Akt)and glucose transporter 4(GLUT4)in livers were assessed by Western blot. Result: Compared with normal group,model group showed liver and pancreas injury. FBG,GSP,TC,TG,LDL-C,FINS and MDA levels in serum were significantly increased(P<0.01),HDL-C and SOD levels in serum were significantly decreased(P<0.05),liver glycogen content was significantly decreased(P<0.01),as well as expression of IR,IRS-1,p-PI3 K/PI3 K,p-Akt/Akt and GLUT4 protein in liver tissues were significantly decreased(P<0.01). Compared with model group,TFE was able to relieve liver and pancreas injury,while the levels of FBG,GSP,TC,TG,FINS and MDA in serum were significantly decreased(P<0.05),HDL-C and SOD levels liver were significantly increased(P<0.05),liver glycogen content was significantly increased(P<0.01),and the expressions of IRS-1,p-PI3 K/PI3 K,p-Akt/Akt and GLUT4 protein in liver tissues were significantly up-regulated(P<0.05). Conclusion: These findings indicate that TFE has the potential to reduce blood sugar and alleviates insulin resistance through the PI3 K/Akt signalin

关 键 词：翻白草总黄酮 DB/DB小鼠 2型糖尿病 糖脂代谢 磷脂酰肌醇-3激酶(PI3K)/蛋白激酶B(Akt) 

分 类 号：R2-0[医药卫生—中医学] R289[医药卫生—方剂学]