降糖丸抑制TGF-β1改善糖尿病肾病小鼠肾损伤及纤维化  

Chinese Traditional Medicine Jiangtang Wan ameliorates kidney injury and fibrosis in mice with diabetic kidney disease via inhibiting TGF-β1

作　　者：任宇晴 唐堂 李颖 段应铃 李宁 代睿欣 范辉 兰天 REN Yu-qing;TANG Tang;LI ying;DUAN Ying-ling;LI Ning;DAI Rui-xin;FAN Hui;LAN Tian(Institute of Chinese Medicine,Guangdong Pharmaceutical University,Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine,Key Laboratory of Glucolipid Metabolic Disorder,Ministry of Education,Guangdong TCM Key Laboratory for Metabolic Diseases;School of Pharmacy,Guangdong Pharmaceutical University;Dai Ruixin Clinic of Traditional Chinese Medicine,Guangzhou 510006,China)

机构地区：[1]广东药科大学中医药研究院、广东省代谢病中西医结合研究中心、糖脂代谢病教育部重点实验室、广东省代谢性疾病中医药防治重点实验室 [2]广东药科大学药学院 [3]代睿欣中医诊所,广东广州510006

出　　处：《中国药理学通报》2023年第10期1988-1993,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81870420)。

摘　　要：目的探讨降糖丸对糖尿病肾病小鼠的治疗作用,研究其改善糖尿病肾病肾损伤及纤维化的分子机制。方法C57BL/6小鼠随机分为4组,分别为正常组、模型组、二甲双胍组和降糖丸组。造模小鼠腹腔注射链脲佐菌素(streptozotocin,STZ)合并高脂喂养诱导糖尿病肾病模型,持续8周。记录小鼠体质量、空腹血糖变化;检测尿蛋白、血肌酐评价肾功能;检测血清TC、TG评价脂代谢情况;HE、PAS、Masson染色观察肾脏病理变化;IHC检测小鼠肾组织纤维黏连蛋白(fibronectin,FN)蛋白表达;RT-PCR检测FN、TGF-β1、CollagenⅣ的mRNA表达水平;Western blot检测小鼠肾脏中FN、Smad 3及p-Smad 3蛋白的表达。结果与正常组相比,模型组空腹血糖明显升高(P<0.01);24 h尿量、24 h尿蛋白含量、血肌酐值、血清TC、TG明显升高(P<0.01),糖原堆积、间质纤维化明显增加;小鼠肾组织中FN蛋白表达明显增多(P<0.01);FN、TGF-β1与CollagenⅣ的mRNA表达明显升高(P<0.01);小鼠肾脏中FN、Smad 3及p-Smad 3蛋白的表达量明显升高(P<0.01或P<0.05)。与模型组相比,降糖丸组能够明显逆转上述变化。结论降糖丸能够有效地改善STZ合并高脂饮食诱导的小鼠糖尿病肾病,其机制可能是通过抑制FN及TGF-β1的表达从而改善肾间质纤维化。Aim To investigate the therapeutic effect of Jiangtang Wan(JTW)on mice with diabetic kidney disease(DKD)and to explore its potential molecular mechanism on ameliorating renal injury and fibrosis.Methods C57BL/6 mice were randomly divided into four groups:the control group,the model group,JTW group(1250 mg·kg^(-1))and metformin group(200 mg·kg^(-1)).Except for the control group,the mice in other groups were intraperitoneally injected with STZ and fed with high-fat diet for eight weeks to induce diabetic kidney disease model.Body weight and fasting blood glucose were recorded for each group of mice.The renal damage was detected by 24 h albuminuria and serum creatinine level.Serum TC(triglyceride)and TG(total cholesterol)level were detected to evaluate lipid metabolism.The renal morphological changes were observed by HE,PAS and Masson staining.The expression of fibronectin(FN)in the renal tissue of DKD mice was detected by immunohistochemistry.The mRNA expressions of fibronectin(FN)and transforming growth factor-β1(TGF-β1)were detected by fluorescence quantitative PCR.The protein expressions of kidney FN,Smad 3 and p-Smad 3 were detected by Western blot.Results The fasting blood glucose was significantly raised in the model group compared with the control group(P<0.01).24 h albuminuria,serum creatinine,serum TC,TG significantly increased(P<0.01)in the model group,and glycogen accumulation and interstitial fibrosis significantly increased in the model group.The expression of fibronectin(FN)in renal tissue was significantly elevated in the model group(P<0.01).The mRNA expressions of FN,TGF-β1 and collagenⅣsignificantly increased in the model group(P<0.01).The protein expression of FN,Smad 3 and p-Smad 3 in renal significantly increased in the model group(P<0.01 or P<0.05).Compared with the model group,JTW group could significantly reverse the above-mentioned indexes.Conclusions JTW can improve diabetic kidney disease induced by STZ and high-fat diet in mice,and its mechanism may be via reducing FN and TGF-β1 a

关 键 词：降糖丸 糖尿病肾病 肾损伤 间质纤维化 纤维粘连蛋白 转化生长因子-Β1 

分 类 号：R-332[医药卫生] R322.61R285.5R692.39R977.6