TGF-βSmadRUNX3信号通路在糖尿病肾病大鼠肾小管上皮细胞EMT过程中的作用  

The role of TGF-β/Smad/RUNX3 signaling pathway in the EMT process of renal tubularepithelial cells in diabetic nephropathy rats

作　　者：潘春勤[1] 周学才[2] 杜鹏举 刘杰[1] PAN Chunqin;ZHOU Xuecai;DU Pengju;LIU Jie(Department of Nephrology,Xiantao First People's Hospital Affiliated to Changjiang University, Xiantao 433000,Hubei, China;Department of Cardiovascular Medicine,Xiantao First People's Hospital Affiliated to Changjiang University,Xiantao 433000,Hubei,China)

机构地区：[1]长江大学附属仙桃市第一人民医院肾病内科,湖北仙桃433000 [2]长江大学附属仙桃市第一人民医院心血管内科,湖北仙桃433000

出　　处：《西部医学》2021年第10期1423-1427,1435,共6页Medical Journal of West China

基　　金：湖北省卫生计生委创新团队项目(WJ2017M259)。

摘　　要：目的探讨TGF-β/Smad/RUNX3信号通路在糖尿病肾病(DN)大鼠肾小管上皮细胞-间充质转化(EMT)过程中的作用。方法将45只Wistar雄性大鼠随机分成三组:对照组、模型组和实验组,每组各15只,实验组和模型组制备DN大鼠模型。按照实验分组进行给药。末次给药后,用血糖仪检测各组大鼠血糖含量,全自动生化分析仪检测各组大鼠24 h尿蛋白、血尿素氮及血肌酐含量,过碘酸希夫(PAS)、天狼星红(SR)染色观察各组大鼠肾脏组织病理变化,酶联免疫吸附测定(ELISA)检测各组大鼠血清白介素1β(IL-1β)、白介素6(IL-6)表达水平,蛋白免疫印迹(Western blot)检测各组大鼠肾脏组织α-SMA、E-cadherin、TGF-β1、Smad3、Smad4、RUNX3蛋白表达情况。结果与对照组相比,模型组大鼠肾小管肥大增生,肾间质有炎症细胞浸润现象,肾间质胶原纤维沉积、24 h尿量、24 h尿蛋白、血糖、血尿素氮、血肌酐浓度、血清IL-1β、IL-6表达量、肾脏α-SMA、TGF-β1、Smad3、Smad4蛋白表达显著升高(P<0.05),肾脏E-cadherin、RUNX3蛋白表达显著降低(P<0.05);与模型组相比,实验组大鼠肾小管肥大减轻,炎症细胞减少,肾间质胶原纤维沉积、24 h尿量、24 h尿蛋白、血尿素氮、血肌酐浓度、血清IL-1β、IL-6、肾脏α-SMA、TGF-β1、Smad3、Smad4蛋白表达显著降低(P<0.05),肾脏E-cadherin、RUNX3蛋白表达显著升高(P<0.05)。结论TGF-β抑制剂可通过抑制TGF-β/Smad通路激活促进RUNX3表达,减少糖尿病肾病大鼠肾间质纤维化及促炎因子分泌,抑制肾小管上皮细胞EMT的发展。Objective To study the role of transforming growth factor-β(TGF-β)/Smad/Runt-related transcription factor 3(RUNX3)signaling pathway in the process of epithelial mesenchymal transition(EMT)of renal tubular epithelial cells in diabetic nephropathy(DN)rats.Methods 45 male Wistar rats were randomly divided into:control group,model group and experimental group,with 15 rats in each group.DN rat model was made in experimental group and model group.According to the experimental group for administration.After the last administration,blood glucose was measured by blood glucose meter,the contents of 24h urine protein,blood urea nitrogen and blood creatinine were measured by automatic biochemical analyzer,the renal pathological changes were observed by PAS and SR staining,the expression levels of IL-1βand IL-6 in serum were detected by ELISA,and Western blot was used to detect the expressions ofα-SMA,E-cadherin,TGF-β1,Smad3,Smad4 and RUNX3 in the kidney of rats in each group.Results Compared with the control group,the renal tubules and epithelial structure of the model group were damaged,the renal tubules were hypertrophic,and there was inflammatory cell infiltration in the renal interstitium of the model group were damaged,the renal interstitial collagen deposition,24h urine volume,24h urine protein,blood glucose,blood urea nitrogen,blood creatinine concentration,the expressions of IL-1βand IL-6 in serum,while the protein expressions ofα-SMA,TGF-β1,Smad3 and Smad4 in renal tissue increased significantly(P<0.05),and the protein expressions of E-cadherin and RUNX3 in kidney decreased significantly(P<0.05);Compared with the model group,the renal tubular hypertrophy and inflammatory cells in the experimental group were reduced,the renal interstitial collagen deposition,24h urine volume,24h urine protein,blood urea nitrogen,blood creatinine concentration,the expressions of IL-1βand IL-6 in serum,and the protein expressions ofα-SMA,TGF-β1,Smad3 and Smad4 in renal tissue decreased significantly(P<0.05),while the protein

关 键 词：转化生长因子-β/Smad/Runt相关转录因子3信号通路 糖尿病肾病 上皮细胞-间充质转化 

分 类 号：R587.2[医药卫生—内分泌]