黄芪多糖对糖尿病大鼠肾脏TGF-β1/Smads信号通路的影响  

Effects of astragalus polysaccharide on renal TGF-β1/Smads signaling pathway in rats with diabetes mellitus

作　　者：李承德 王煜[2] 曲敬蓉[2] 张晓俊 毛淑梅[2] 聂克[3] LI Cheng-de;WANG Yu;QU Jing-rong;ZHANG Xiao-jun;MAO Shu-mei;NIE Ke(College of Basic Medical Sciences,Shandong University of Traditional Chinese Medicine,Jinan　250355,China;Dept of Pharmacology,Weifang Medical College,the Key Lab of Applied Pharmacology in Shandong Province,Weifang Shandong　261053,China;Dept of Pharmacology of Chinese Materia Medica,Institute of Traditional Chinese Medicine,Guangdong Pharmaceutical University,Guangzhou Guangdong　510006,China)

机构地区：[1]山东中医药大学基础医学院,山东济南250355 [2]潍坊医学院药理学教研室,山东省重点应用药理学实验室,山东潍坊261053 [3]广东药科大学中药学院中药药理教研室,广东广州510006

出　　处：《中国药理学通报》2018年第4期512-516,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No81673779，81373828)；山东省自然科学基金资助项目(NoZR2009CL045，ZR2011HL066，ZR2013CM033，ZR2015CL029)；山东省教育厅科技计划项目(NoJ15LL54，J16LM11)；山东省中医药管理局项目(No2013-242，2015-237)

摘　　要：目的观察黄芪多糖(astragalus polysaccharide,APS)对糖尿病(diabetes mellitus,DM)大鼠肾脏TGF-β1/Smads信号通路的影响。方法 Wistar大鼠随机分为正常组、糖尿病组(DM组)、APS低、高剂量组。一次性腹腔注射链脲佐菌素(streptozotocin,STZ)制备DM大鼠模型。APS低、高剂量组分别给予200、400 mg·kg^(-1)·d^(-1)APS干预8周。检测大鼠空腹血糖(fasting blood-glucose,FBG)、血肌酐、尿素氮(blood urea nitrogen,BUN)、肾损伤标志物尿肾损伤分子-1(kidney injury molecule-1,KIM-1)、尿骨桥蛋白(osteopontin,OPN)浓度。检测大鼠肾脏TGF-β1、Smad2、p-Smad2、Smad3、p-Smad3、Smad7、基质金属蛋白酶(matrix metalloproteinase,MMP)2、MMP-9、组织金属蛋白酶抑制因子-1(tissue inhibitor of matrix metalloproteinases 1,TIMP-1)、TIMP-2水平。结果与正常组比较,DM组大鼠空腹血糖、血肌酐、尿素氮、尿KIM-1、OPN浓度明显升高;肾脏TGF-β1、Smad2、p-Smad2、Smad3、p-Smad3、TIMP-1、TIMP-2水平明显升高,而肾脏Smad7、MMP-2、MMP-9明显降低。APS明显降低了DM大鼠空腹血糖、血肌酐、尿素氮、尿KIM-1、尿OPN浓度,并抑制了肾脏TGF-β1/Smads信号通路的活性。结论 APS对DM大鼠有肾脏保护作用,其机制可能与抑制DM大鼠肾脏TGF-β1/Smad信号通路有关。Aim To investigate the effects of astragalus polysaccharide(APS)on renal TGF-β1/Smads signaling pathway in rats with diabetes mellitus(DM).Methods Wistar rats were randomly divided into normal group,DM group,APS low dose(APS-low)group and APS high dose(APS-high)group.Rats in APS-low group and APS-high group respectively received 200 and 400 mg·kg-1·d-1 APS for 8 weeks.Concentrations of fasting blood-glucose(FBG),blood urea nitrogen and creatinine,as well as urinary kidney injury molecule-1(KIM-1)and osteopontin(OPN)were measured.Levels of TGF-β1,Smad2,phosphorylated Smad2(p-Smad2),Smad3,phosphorylated Smad3(p-Smad3),Smad7,matrix metalloproteinase(MMP)2,MMP-9,tissue inhibitor of matrix metalloproteinases(TIMP)-1 and TIMP-2 were investigated.Results Compared to control group,DM group had higher levels of FBG,blood urea nitrogen,creatinine KIM-1,OPN,TGF-β1,Smad2,p-Smad2,Smad3,p-Smad3,TIMP-1 and TIMP-2,but lower levels of Smad7,MMP-2 and MMP-9.APS significantly decreased the levels of FBG,blood urea nitrogen,creatinine KIM-1 and OPN,as well as inhibited the activity of TGF-β1/Smads signaling pathway.Conclusion The renoprotective effects of APS might be associated with the inhibition of TGF-β1/Smads signaling pathway.

关 键 词：黄芪多糖 糖尿病 肾损伤 TGF-β1 SMADS MMP TIMP 

分 类 号：R-332[医药卫生] R284.1