丹蒌片降低db/db小鼠肝脏脂肪生成及炎症反应改善胰岛素抵抗的作用研究  

Effect of Danlou Tablets on alleviating hepatic adipogenesis,inflammatory response,and insulin resistance in db/db mice

作　　者：庞雅芬 黄明[1,2] 李琳[1,2] 赵鑫[1,2] 张红霞[3] 李玉红[1,2] PANG Ya-fen;HUANG Ming;LI Lin;ZHAO Xin;ZHANG Hong-xia;LI Yu-hong(Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;State Key Laboratory of Component-based Chinese Medicine,Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine,Tianjin 300250,China)

机构地区：[1]天津中医药大学,天津301617 [2]天津中医药大学组分中药国家重点实验室,天津301617 [3]天津中医药大学第二附属医院,天津300250

出　　处：《中国中药杂志》2022年第12期3320-3327,共8页China Journal of Chinese Materia Medica

基　　金：天津市自然科学基金青年基金项目(20JCQNJC00160);国家自然科学基金项目(81774017);全国中医药创新骨干人才培训项目。

摘　　要：该文旨在研究丹蒌片(Danlou Tablets,DLT)对2型糖尿病db/db小鼠胰岛素抵抗的作用及潜在机制。将db/db雄性小鼠随机分成模型对照组、二甲双胍组(盐酸二甲双胍片100 mg·kg^(-1))和丹蒌片组(丹蒌片1 g·kg^(-1)),另取C57BL/6J小鼠作为正常对照组。二甲双胍组和丹蒌片组小鼠灌胃给予相应剂量药物,每日1次,连续给药16周。通过检测小鼠空腹血糖(FBG)、葡萄糖耐量及胰岛素耐量评价丹蒌片对糖尿病小鼠血糖及胰岛素抵抗的影响;通过检测血清游离脂肪酸(NEFA)、甘油三酯(TG)、总胆固醇(TC)含量,评价丹蒌片对糖尿病小鼠血脂的影响;通过检测小鼠肝脏指数及肾周脂肪指数评价丹蒌片对非脂肪组织与脂肪组织中脂质蓄积的影响;基于IRS-1/PI3K/Akt胰岛素信号通路,采用蛋白免疫印迹(Western blot)法检测小鼠肝脏组织中胰岛素受体β(IRβ)、磷酸化胰岛素受体β(p-IRβ)、磷脂酰肌醇3-激酶(PI3K)、胰岛素受体底物-1(IRS-1)蛋白表达水平,探讨丹蒌片改善糖尿病小鼠胰岛素抵抗的作用机制;基于SREBP-1/FAS信号通路,检测固醇调控元件结合蛋白-1(SREBP-1)蛋白表达水平以及固醇调节元件结合蛋白-1c(SREBP-1c)、脂肪酸合成酶(FAS)、乙酰辅酶A羧化酶(ACC)、二酰甘油酰基转移酶-1(Dgat1)、二酰甘油酰基转移酶-2(Dgat2)基因表达水平,探讨丹蒌片对糖尿病小鼠脂质代谢的影响;通过实时定量PCR(RT-PCR)法检测小鼠肝脏中与炎症相关的半乳糖凝集素-3(Gal-3)、白细胞介素-6(IL-6)、单核细胞趋化蛋白-1(MCP-1)基因表达水平,评价丹蒌片对糖尿病小鼠炎症反应的影响。结果表明,丹蒌片可显著降低糖尿病小鼠血糖、血脂水平,具有改善糖尿病小鼠胰岛素抵抗的作用。与模型对照组相比,丹蒌片可显著提高糖尿病小鼠肝脏p-IRβ、PI3K和IRS-1蛋白表达水平(P<0.05或P<0.01),并降低肝脏SREBP-1蛋白表达水平(P<0.05);丹蒌片还能下调糖尿病小鼠肝�This study explored the effect and potential mechanism of Danlou Tablets(DLT)on insulin resistance in db/db mice with type 2 diabetic mellitus(T2 DM).The db/db male mice were randomly assigned into model control(MC)group,metformin(MET,tablet,100 mg·kg^(-1))group,and DLT(1 g·kg^(-1))group,and C57 BL/6 J mice were taken as normal control(NC)group.The mice in the MET group and DLT group were given corresponding drugs by gavage once a day for 16 weeks.The fasting blood glucose,glucose tolerance,and insulin tolerance were measured to evaluate the effect of DLT on blood glucose and insulin resistance in diabetic mice.The serum free fatty acid,triacylglycerol,and total cholesterol levels were determined to evaluate the effect of DLT on blood lipids in diabetic mice.The liver index and perirenal fat index were calculated to measure the effect of DLT on lipid accumulation in non-adipose tissue and adipose tissue.Western blot was performed to determine the protein levels of insulin receptor-β(IRβ),phospho-IRβ(p-IRβ),phosphatidylinositol 3-kinase(PI3 K),and insulin receptor substrate-1(IRS-1)involved in IRS-1/PI3 K/Akt signaling pathway in the livers of mice to reveal the mechanism of DLT in alleviating insulin resistance in diabetic mice.The protein levels of sterol regulatory element binding protein-1(SREBP-1)and the mRNA levels of sterol regulatory element binding protein-1 c(SREBP-1 c),fatty acid synthase(FAS),acetyl-CoA carboxylase(ACC),diacylglycerol acyltransferase-1(Dgat1),and diacylglycerol acyltransferase-2(Dgat2)involved in the SREBP-1/FAS signaling pathway were detected to evaluate the effect of DLT on lipid metabolism in diabetic mice.Real-time quantitative PCR was employed to determine the mRNA levels of galectin-3(Gal-3),interleukin-6(IL-6),and monocyte chemoattractant protein-1(MCP-1)in mouse liver to evaluate the effect of DLT on inflammatory response in diabetic mice.The results showed that DLT significantly reduced the blood glucose and lipid levels and alleviated the insulin resistance in diabetic

关 键 词：丹蒌片 2型糖尿病 胰岛素抵抗 IRS-1/PI3K/Akt SREBP-1/FAS 炎症反应 

分 类 号：R285.5[医药卫生—中药学]