摘要
研究葛根芩连汤(GQD)对糖尿病大鼠棕色脂肪组织(BAT)分化及能量代谢的影响。给药干预高脂喂养加小剂量链脲佐菌素(STZ)诱导糖尿病大鼠13周,在确认降糖药效基础上,提取大鼠肩胛骨周围BAT总RNA,qPCR法检测核转录基因Prdm16、Pparγc1α、Pparα、Pparγ和Sirt1,BAT标志基因Ucp1、Cidea、Dio2和能量消耗基因Ampkα2,脂肪分泌因子Adpn、Fndc5、Angptl8、IL-6和Rbp4表达。IPA通路软件分析qPCR数据干预差异。提取BAT总蛋白,Western blot法检测PRDM16、PGC1α、PPARγ、PPARα、SIRT1、ChREBP、AMPKα、UCP1、ADPN、NRG4、GLUT1和GLUT4等表达水平。结果显示,与模型组相比,GQD显著上调糖尿病大鼠Pparγc1α、Pparα、Pparγ、Ucp1、Cidea、Ampkα2、Dio2、Fndc5、Rbp4和Angptl8表达水平(P<0.05),显著下调Adpn和IL-6表达水平(P<0.05),Prdm16表达有上调趋势(P=0.182),而Sirt1表达有下调趋势(P=0.104)。IPA通路功能分析显示GQD促进脂肪组织棕色化,激活PPARα/RXRα和SIRT1信号通路,减少脂质积累。与正常组相比,模型组PRDM16、PGC1α、PPARα、PPARγ、SIRT1、ChREBP、AMPKα、UCP1、GLUT1、GLUT4和NRG4蛋白表达下调(P<0.01),给药后表达上调(P<0.05);与正常组相比,模型组ADPN蛋白表达上调(P<0.01),给药后表达下调(P<0.01)。研究表明GQD促进BAT分化成熟,增加能量消耗,有助于减轻机体糖脂代谢紊乱,改善糖尿病症状。
This study explored the molecular mechanism underlying the Gegen Qinlian Decoction(GQD)promoting the differentiation of brown adipose tissue(BAT)to improve glucose and lipid metabolism disorders in diabetic rats.After the hypoglycemic effect of GQD on diabetic rats induced by high-fat diet combined with a low dose of streptozotocin was confirmed,the total RNA of rat BAT around scapula was extracted.Nuclear transcription genes Prdm16,Pparγc1α,Pparα,Pparγand Sirt1,BAT marker genes Ucp1,Cidea and Dio2,energy expenditure gene Ampkα2 as well as BAT secretion factors Adpn,Fndc5,Angptl8,IL-6 and Rbp4 were detected by qPCR,then were analyzed by IPA software.Afterward,the total protein from rat BAT was extracted,and PRDM16,PGC1α,PPARγ,PPARα,SIRT1,ChREBP,AMPKα,UCP1,ADPN,NRG4,GLUT1 and GLUT4 were detected by Western blot.The mRNA expression levels of Pparγc1α,Pparα,Pparγ,Ucp1,Cidea,Ampkα2,Dio2,Fndc5,Rbp4 and Angptl8 were significantly increased(P<0.05)and those of Adpn and IL-6 were significantly decreased(P<0.05)in the GQD group compared with the diabetic group.In addition,Sirt1 showed a downward trend(P=0.104),whereas Prdm16 tended to be up-regulated(P=0.182)in the GQD group.IPA canonical pathway analysis and diseases-and-functions analysis suggested that GQD activated PPARα/RXRαand SIRT1 signaling pathways to promote the differentiation of BAT and reduce the excessive lipid accumulation.Moreover,the protein expression levels of PRDM16,PGC1α,PPARα,PPARγ,SIRT1,ChREBP,AMPKα,UCP1,GLUT1,GLUT4 and NRG4 were significantly decreased in the diabetic group(P<0.01),which were elevated after GQD intervention(P<0.05).Unexpectedly,the expression of ADPN protein in the diabetic group was up-regulated(P<0.01)as compared with the control group,which was down-regulated after the administration with GQD(P<0.01).This study indicated that GQD promoted BAT differentiation and maturity to increase energy consumption,which reduced the glucose and lipid metabolism disorders and thereby improved diabetes symptoms.
作者
张小清
许文华
肖鑫
丁浚峰
姜月
涂珺
ZHANG Xiao-qing;XU Wen-hua;XIAO Xin;DING Jun-feng;JIANG Yue;TU Jun(Jiangxi Province Key Laboratory of Traditional Chinese Medicine Etiopathogenisis&Research Center for Differentiation and Development of Traditional Chinese Medicine Basic Theory,Jiangxi University of Chinese Medicine,Nanchang 330004,China;Key Laboratory of Traditional Chinese Medicine Pharmacology of Jiangxi Province,Nanchang 330004,China)
出处
《中国中药杂志》
CAS
CSCD
北大核心
2021年第17期4462-4470,共9页
China Journal of Chinese Materia Medica
基金
国家自然科学基金项目(82160838,81960809)
江西省中医药管理局科技计划项目(SZYYB20205136)。
关键词
棕色脂肪组织
糖脂代谢
糖尿病
能量消耗
葛根芩连汤
brown adipose tissue
glucose and lipid metabolism
diabetes
energy consumption
Gegen Qinlian Decoction
作者简介
通信作者:涂珺,教授,研究方向为药理/中西医结合基础,Email:jtu2012@163.com;张小清,硕士研究生,E-mail:13640953007@qq.com。
