降糖消渴颗粒对糖尿病小鼠肝脏AMPKα/NF-κB信号通路的影响  

Effects of Jiangtang Xiaoke Granules(降糖消渴颗粒)on Liver AMPKα/NF-κB Signaling Pathway in Diabetic Mice

作　　者：张毅[1] 赵丹丹[2] 莫芳芳[2] 高思华[2] ZHANG Yi;ZHAO Dandan;MO Fangfang;GAO Sihua(Beijing Open University,Beijing 100081,China;Beijing University of Chinese Medicine,Beijing 100029,China)

机构地区：[1]北京开放大学,北京100081 [2]北京中医药大学,北京100029

出　　处：《山东中医药大学学报》2022年第5期626-632,共7页Journal of Shandong University of Traditional Chinese Medicine

基　　金：国家中医药领军人才支持计划——岐黄学者项目(编号:10400633210005);重大新药创制子课题项目(编号:2012ZX09103201-005)。

摘　　要：目的:检测降糖消渴颗粒干预后的2型糖尿病小鼠肝组织胰岛素信号通路、腺苷酸活化蛋白激酶α(AMPKα)信号通路、核因子κB(NF-κB)信号通路相关指标表达的变化,探讨其改善糖尿病状态下肝脏脂代谢的可能途径。方法:40只8周龄雄性KK-Ay小鼠,高脂饲料喂养4周,诱导2型糖尿病发生,尾静脉取血测量空腹血糖,以空腹血糖≥13.9 mmol/L作为糖尿病成模标准。将40只糖尿病小鼠随机分为模型组、吡格列酮组及降糖消渴颗粒低(1.75 g/kg)、中(3.50 g/kg)、高(7.00 g/kg)剂量组,每组8只,灌胃给药治疗10周。8只同周龄雄性C57BL/6J小鼠作为正常组,普通饲料喂养。治疗结束后,肝组织取材,实时荧光定量聚合酶链反应(RT-qPCR)检测小鼠肝脏胰岛素受体底物-1(IRS-1)、蛋白激酶Cε(PKCε)、腺苷酸活化蛋白激酶α(AMPKα)、过氧化物酶体增殖物激活受体α(PPARα)、NF-κB、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)的mRNA表达情况。结果:与正常组比较,模型组NF-κB、TNF-αmRNA上升,IRS-1、AMPKα、PPARαmRNA降低,差异均有统计学意义(P<0.01)。与模型组比较,吡格列酮组IRS-1、AMPKαmRNA上升,差异均有统计学意义(P<0.01);降糖消渴颗粒高剂量组PKCεmRNA降低,PPARαmRNA上升,差异均具有统计学意义(P<0.01);降糖消渴颗粒中剂量组AMPKαmRNA上升,NF-κB、TNF-αmRNA降低,差异均有统计学意义(P<0.01或P<0.05);降糖消渴颗粒低剂量组AMPKαmRNA上升,NF-κB、TNF-αmRNA降低,差异均具有统计学意义(P<0.01或P<0.05)。结论:降糖消渴颗粒可上调糖尿病状态下小鼠肝细胞内AMPKαmRNA的表达,同时抑制NF-κB炎症信号通路的激活,调节肝脏脂质代谢;其中低、中剂量降糖消渴颗粒综合效果较好。Objective:To detect the expression changes of insulin signaling pathway,adenosine-activated protein kinase(AMPK)signaling pathway and nuclear factor κB(NF-κB)signaling pathway in liver tissue of type 2 diabetic mice after Jiangtang Xiaoke Granules(降糖消渴颗粒)intervention,and to explore the possible way of improving liver lipid metabolism in diabetic mice.Methods:Forty 8-week-old male KK-Ay mice were fed a high-fat diet for 4 weeks to induce type 2 diabetes model.Then,blood samples were collected from tail vein to measure fasting blood glucose,and fasting blood glucose≥13.9 mmol/L was used as the standard for diabetes modeling.Forty diabetic mice were randomly divided into model group,pioglitazone group and Jiangtang Xiaoke Granules low-dose(1.75 g/kg),medium-dose(3.50 g/kg)and high-dose(7.00 g/kg)groups,with 8 mice in each group,and treated by intragastric administration for 10 weeks.Eight male C57BL/6J mice aged the same week were fed with normal diet as the normal group.At the end of the treatment,liver tissue was taken,the mRNA expressions of IRS-1,PKCε,AMPKα,PPARα,NF-κB,TNF-α and IL-1β were examined by real time polymerase chain reaction(RT-qPCR).Results:Compared with the normal group,mRNA expressions of NF-κB and TNF-α in model groups were increased(P<0.01)while mRNA expressions of IRS-1,AMPKα and PPARα were decreased(P<0.01).Compared with the model group,mRNA expressions of IRS-1 and AMPKαin pioglitazone group were increased(P<0.01).The mRNA expression of PKCε in Jiangtang Xiaoke Granules high-dose group was decreased while mRNA expression of PPARα was increased(P<0.01).The mRNA expression of AMPKαin Jiangtang Xiaoke Granules medium-dose group was increased while mRNA expressions of NF-κB and TNF-α were decreased(P<0.01 or P<0.05).The mRNA expression of AMPKαin Jiangtang Xiaoke Granules low-dose group was increased while mRNA expressions of NF-κB and TNF-α were decreased(P<0.01 or P<0.05).Conclusions:Jiangtang Xiaoke Granules can up-regulate the mRNA expression of AMPKαin liv

关 键 词：降糖消渴颗粒 2型糖尿病 非酒精性脂肪性肝病 核因子ΚB 腺苷酸活化蛋白激酶α 胰岛素抵抗 

分 类 号：R285.5[医药卫生—中药学]