非诺贝特通过介导TGF-β1/Smad3信号通路对糖尿病肾病大鼠肾功能的保护作用研究  

Protective Effect of Fenofibrate on Renal Function of Rats with Diabetic Nephropathy by Mediating TGF-β1/Smad3 Signaling Pathway

作　　者：阮华玲[1] 郭昆全[1] 杨坤[1] 叶林秀[1] 阎劲松[1] 周丽荣[1] RUAN Hua-ling;GUO Kun-quan;YANG Kun;YE Lin-xiu;YAN Jin-song;ZHOU Li-rong(Department of Endocrinology and Metabolism,Sinopharm Dongfeng General Hospital,Hubei University of Medicine,Shiyan,Hubei 442008,China)

机构地区：[1]湖北医药学院附属国药东风总医院内分泌代谢科,湖北十堰442008

出　　处：《解放军医药杂志》2021年第7期7-11,共5页Medical & Pharmaceutical Journal of Chinese People’s Liberation Army

基　　金：湖北省卫生厅青年科技人才项目(2018CFB354)。

摘　　要：目的研究非诺贝特保护糖尿病肾病(DN)大鼠肾功能的作用机制。方法将30只4周龄SD大鼠分为正常对照组、模型组和非诺贝特组,模型组和非诺贝特组大鼠经高糖高脂饲料饲养联合链脲佐菌素腹腔注射构建DN大鼠模型,非诺贝特组大鼠给予非诺贝特50 mg/kg腹腔注射,连续干预8周。干预8周后检测各组大鼠血脂、肾功能指标水平,取肾组织行HE和Masson染色观察肾组织病理改变及纤维化程度,Western blot法检测肾组织中α-平滑肌肌动蛋白(α-SMA)、纤溶酶原激活物抑制剂-1(PAI-1)、金属蛋白酶组织抑制剂-1(TIMP-1)、TGF-β1/Smad3信号通路相关蛋白表达水平。结果模型组大鼠肾脏指数(KI)、肾小球面积(GA)、纤维化程度、24 h尿蛋白定量、三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)及α-SMA、PAI-1、TIMP-1、转化生长因子-β1(TGF-β1)、p-Smad3/Smad3蛋白表达水平均显著升高(P<0.05),肌酐清除率(Ccr)、高密度脂蛋白胆固醇(HDL-C)及Smad7蛋白表达水平显著降低(P<0.05);与模型组大鼠相比,非诺贝特组大鼠KI、GA、纤维化程度、24 h尿蛋白定量、TG、TC、LDL-C及α-SMA、PAI-1、TIMP-1、TGF-β1、p-Smad3/Smad3蛋白表达水平均显著降低(P<0.05),Ccr、HDL-C及Smad7蛋白表达水平显著升高(P<0.05)。结论非诺贝特可能通过降低DN大鼠血脂水平抑制TGF-β1/Smad3信号通路激活,降低促纤维化相关蛋白表达,从而保护肾功能。Objective To study the mechanism of Fenofibrate(Fen)in protection of renal function in rats with diabetic nephropathy(DN).Methods A total of 30 SD rats aged 4 weeks were divided into normal control group,model group and Fen group.Model and Fen groups were fed with high-sugar and high-fat diet combined with intraperitoneal injection of Streptozotocin to construct DN rat models,while Fen group was injected intraperitoneally with 50 mg/kg Fen,and intervention duration was 8 weeks continuously.After intervention for 8 weeks in each group,levels of blood lipid and renal function indexes were measured;renal tissues were taken out and stained with HE and Masson to observe pathological changes and fibrosis degree;Western blot method was used to detect expressions of related proteins theα-Smooth muscle actin(α-SMA),plasminogen activator inhibitor-1(PAI-1),tissue inhibitor of metalloproteinase-1(TIMP-1)and TGF-β1/Smad3 signaling pathway in renal tissues.Results In model group,values of kidney index(KI),glomerular area(GA),fibrosis degree,24-h-urinary protein quantification,triacylglycerol(TG),total cholesterol(TC),low density lipoprotein cholesterol(LDL-C),α-SMA,PAI-1,TIMP-1,transforming growth factor-β1(TGF-β1)and p-Smad3/Smad3 protein levels were significantly increased compared with those in normal control group(P<0.05),while protein levels of creatinine clearance(Ccr),high density lipoprotein cholesferol(HDL-C)and Smad7 were significantly decreased(P<0.05).Compared with those in model group,values of KI,GA,fibrosis degree,24-h-urinary protein quantification,TG,TC and LDL-C,and protein levels ofα-SMA,PAI-1,TIMP-1,TGF-β1 and p-Smad3/Smad3 were significantly decreased(P<0.05),while protein levels of Ccr,HDL-C and Smad7 were significantly increased in Fen group(P<0.05).Conclusion Fenofibrate may inhibit the activation of TGF-β1/Smad3 signaling pathway by decreasing blood lipid levels of DN rats,and protect renal function by reducing expressions of pro-fibrosis related proteins in DN rats.

关 键 词：糖尿病肾病 大鼠 非诺贝特 转化生长因子-Β1 SMAD3 肾纤维化 

分 类 号：R587.24[医药卫生—内分泌] R-332[医药卫生—内科学]