摘要
目的探讨有氧运动对自发性高血压大鼠(SHR)肾脏纤维化的影响并探讨肾小管上皮-间质转化(EMT)在其间的作用机制。方法将10只Wistar-Kyoto大鼠作为正常血压对照组(WKY),30只雄性SHR按照随机数字表法分为高血压安静组(SHR-S)和高血压运动组(SHR-E),每组15只。WKY和SHR-S组在鼠笼内安静饲养,SHR-E组进行8周跑台运动。实验后,利用无创血压仪检测尾动脉血压;测定24 h尿蛋白(UP)、血尿素氮(BUN)和血清肌酐(SCr)含量评价肾功能;Masson染色进行肾脏病理组织学观察并获取纤维化指数(FI);免疫印迹测定转化生长因子β1(TGF-β1)、磷酸化Smad2/3(p-Smad2/3)、α-平滑肌肌动蛋白(α-SMA)和E-钙黏蛋白(E-CA)表达量。结果与WKY组比较,SHR-S组血压[SBP:(177.3±17.2)mmHg vs.(110.6±13.3)mmHg,P<0.05;DBP:(108.1±6.3)mmHg vs.(75.6±4.9)mmHg,P<0.05;MAP:(131.1±7.4)mmHg vs.(87.3±4.7)mmHg,P<0.05]、肾脏FI[(7.87±1.89)%vs.(0.43±0.05)%,P<0.05]、UP[(197.3±41.6)mg/24 h vs.(89.2±9.5)mg/24 h,P<0.05]、BUN[(14.3±2.9)mmol/L vs.(4.9±1.0)mmol/L,P<0.05]和SCr[(98.6±10.1)μmol/L vs.(35.8±4.3)μmol/L,P<0.05]升高,TGF-β1、p-Smad2、p-Smad3和α-SMA蛋白表达上调(P<0.05),E-CA蛋白表达下调(P<0.05);与SHR-S组比较,SHR-E组血压[SBP:(152.3±14.2)mmHg vs.(177.3±17.2)mmHg,P<0.05;DBP:(93.1±9.7)mmHg vs.(108.1±6.3)mmHg,P<0.05;MAP:(112.8±7.9)mmHg vs.(131.1±7.4)mmHg,P<0.05]、肾脏FI[(3.02±0.91)%vs.(7.87±1.89)%,P<0.05]、UP[(127.9±25.7)mg/24 h vs.(197.3±41.6)mg/24 h,P<0.05]、BUN[(6.8±1.7)mmol/L vs.(14.3±2.9)mmol/L,P<0.05]和SCr[(50.3±6.0)μmol/L vs.(98.6±10.1)μmol/L,P<0.05]下降,TGF-β1、p-Smad2、p-Smad3和α-SMA蛋白表达下调(P<0.05),E-CA蛋白表达上调(P<0.05)。结论有氧运动可能通过调控TGF-β1/Smad信号途径抑制高血压肾病大鼠肾小管EMT,进而改善肾脏纤维化并提高肾功能。
Objective To explore the effect of aerobic exercise on renal fibrosis in spontaneously hypertensive rats(SHRs)and investigate the mechanism of renal tubular epithelial-interstitial transformation(EMT)in the above process so as to facilitate targeted exercise prescriptions for patients with hypertensive nephropathy.Methods Ten Wistar-Kyoto rats were used as the normal blood pressure control group(WKY),while another 30 male SHRs were randomly divided into the hypertensive sedentary group(SHR-S)and hypertensive exercise group(SHR-E).The rats in WKY and SHR-S groups were reared quietly in cages,while those in the SHR-E group were trained on a treadmill for 8 weeks.After the experiment,caudal artery blood pressure was measured by a non-invasive sphygmomanometer while 24-hour urinary protein(UP),blood urea nitrogen(BUN)and serum creatinine(SCr)were measured to evaluate renal function.Renal histopathology was observed with Masson staining and the fibrosis index(FI)was obtained.The expressions of transforming growth factor-β1(TGF-β1),phosphorylated Smad2/3(p-Smad2/3),α-smooth muscle actin(α-SMA)and E-cadherin(E-CA)were determined by Western Blotting.Results Compared with the WKY group,blood pressure[SBP:(177.3±17.2)mmHg vs.(110.6±13.3)mmHg,P<0.05;DBP:(108.1±6.3)mmHg vs.(75.6±4.9)mmHg,P<0.05;MAP:(131.1±7.4)mmHg vs.(87.3±4.7)mmHg,P<0.05],renal FI[(7.87±1.89)%vs.(0.43±0.05)%,P<0.05],UP[(197.3±41.6)mg/24 h vs.(89.2±9.5)mg/24 h,P<0.05],BUN[(14.3±2.9)mmol/L vs.(4.9±1.0)mmol/L,P<0.05]and SCr[(98.6±10.1)μmol/L vs.(35.8±4.3)μmol/L,P<0.05]increased,TGF-β1,p-Smad2,p-Smad3 andα-SMA protein expression up-regulated(P<0.05)while E-CA protein expression down-regulated(P<0.05)in SHR-S group.Compared with SHR-S group,blood pressure[SBP:(152.3±14.2)mmHg vs.(177.3±17.2)mmHg,P<0.05;DBP:(93.1±9.7)mmHg vs.(108.1±6.3)mmHg,P<0.05;MAP:(112.8±7.9)mmHg vs.(131.1±7.4)mmHg,P<0.05],renal FI[(3.02±0.91)%vs.(7.87±1.89)%,P<0.05],UP[(127.9±25.7)mg/24 h vs.(197.3±41.6)mg/24 h.P<0.05],BUN[(6.8±1.7)mmol/L vs.(14.3±2.9)mmol/L,P<0.05]and SCr[(50.3±6.0)μmol/L vs.(98.6±10.1)μmol/L,P<0.05]decreased,TGF-β1,p-Smad2 p-Smad3 andα-SMA protein expressions down-regulated(P<0.05)and E-CA protein expression up-regulated(P<0.05)in SHR-E group.Conclusions Aerobic exercise may improve renal fibrosis by inhibiting renal tubular EMT via regulation of TGF-β1/Smad signal pathway,thus enhancing renal function in rats with hypertensive nephropathy.
作者
彭朋
秦永生
王大宁
马刚
何瑞波
刘佰川
李应森
何瑞波
PENG Peng;QIN Yongsheng;WANG Daning;MA Gang;LIU Baichuan;LI Yingsen;HE Ruibo(Department of Health Service,Logistics University of Chinese People’s Armed Police Force,Tianjin 300309,China;No.5 Team,Second Brigade,Logistics University of Chinese People’s Armed Police Force,Tianjin 300309,China)
出处
《武警医学》
CAS
2021年第1期26-29,33,共5页
Medical Journal of the Chinese People's Armed Police Force
基金
天津市自然科学基金项目(17JCYBJC27400)
关键词
有氧运动
高血压
高血压肾病
肾脏纤维化
肾小管上皮-间质转化
aerobic exercise
hypertension
hypertensive nephropathy
renal fibrosis
tubular epithelial-mesenchymal transdifferentiation
作者简介
彭朋,博士,讲师;通讯作者:何瑞波,E-mail:13916072@qq.com
