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。
Abstract
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 and α-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 and α-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.
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
Key words
aerobic exercise /
hypertension /
hypertensive nephropathy /
renal fibrosis /
tubular epithelial-mesenchymal transdifferentiation
彭朋, 秦永生, 王大宁, 马刚, 何瑞波, 刘佰川, 李应森, 何瑞波.
有氧运动对自发性高血压大鼠肾脏纤维化的影响[J]. 武警医学. 2021, 32(1): 26-29
PENG Peng, QIN Yongsheng, WANG Daning, MA Gang, LIU Baichuan, LI Yingsen, HE Ruibo.
Effet of aerobic exercise on renal fibrosis in spontaneously hypertensive rats[J]. Medical Journal of the Chinese People Armed Police Forces. 2021, 32(1): 26-29
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基金
天津市自然科学基金项目(17JCYBJC27400)
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