不同强度运动对自发性高血压大鼠肾脏纤维化的影响及作用机制研究  

Effects and Mechanism of Different Exercise Intensity on Renal Fibrosis in Spontaneously Hypertensive Rats

作　　者：付常喜[1] 马刚 李平[1] 彭朋[2] FU Changxi;MA Gang;LI Ping;PENG Peng(Department of Physical Education,Xuzhou Institute of Technology,Xuzhou,Jiangsu 221008,China;Department of Health Service,Logistics University of Chinese People’s Armed Police Forces,Tianjin 300309,China)

机构地区：[1]徐州工程学院体育学院,江苏徐州221008 [2]中国人民武装警察部队后勤学院卫生勤务系,天津300309

出　　处：《首都体育学院学报》2021年第6期638-648,共11页Journal of Capital University of Physical Education and Sports

基　　金：天津市自然科学基金资助项目(17JCYBJC27400)。

摘　　要：对比长期中等强度持续运动(MCE)和高强度间歇运动(HIE)对自发性高血压大鼠(SHR)肾脏纤维化的影响,并探讨胶原代谢通路(合成代谢和分解代谢)在其间的作用机制,研制高血压肾病患者的最佳康复运动处方。方法:45只3月龄雄性SHR随机分为高血压安静组(SHR-S组)、中等强度持续运动组(SHR-M组)、高强度间歇运动组(SHR-H组),同时,将10只Wistar-Kyoto大鼠作为正常血压对照组(WKY组)。WKY组和SHR-S组大鼠在鼠笼内安静饲养,SHR-M组和SHR-H组大鼠分别进行18周相应方式的运动干预。实验后,使用无创血压仪检测尾动脉血压;以血尿素氮(BUN)、血清肌酐(SCr)及24 h尿蛋白含量评价肾功能;使用H-E和Masson染色进行肾脏组织病理学观察,并对肾小管间质损伤进行评分以及计算间质胶原容积分数(CVF);采用Western blot法检测肾脏转化生长因子β_(1)(TGF-β_(1))、磷酸化Smad2/3(p-Smad2/3)、结缔组织生长因子(CTGF)、基质金属蛋白酶-9(MMP-9)和组织金属蛋白酶抑制物-1(TIMP-1)蛋白表达量;采用免疫组织化学检测肾脏α-平滑肌肌动蛋白(α-SMA)表达量。结果:SHR-S组的血压、24 h蛋白尿、BUN、SCr、肾小管间质损伤评分、CVF、TGF-β_(1)、p-Smad2、p-Smad23、CTGF蛋白表达量、TIMP-1蛋白表达量和肾脏α-SMA表达量均高于WKY组(p<0.05),而MMP-9蛋白表达量和MMP-9/TIMP-1比值均低于WKY组(p<0.05);SHR-M组的血压、24 h蛋白尿、BUN、SCr、肾小管间质损伤评分、CVF、TGF-β_(1)、p-Smad2/3、CTGF蛋白表达量、TIMP-1蛋白表达量和肾脏α-SMA表达量均低于SHR-S组(p<0.05),而MMP-9蛋白表达量和MMP-9/TIMP-1比值均高于SHR-S组(p<0.05);SHR-H组的肾小管间质损伤评分和CVF均高于SHR-S组(p<0.05),但是血压、肾功能、TGF-β_(1)、p-Smad2、p-Smad3、CTGF蛋白表达量及肾脏α-SMA表达量相较SHR-S组均无显著差异(p>0.05);SHR-H组的血压、肾功能、肾小管间质损伤评分、CVF、TGF-β_(1)、p-Smad2、p-Smad3、CTo analyze the effects of long-term moderate intensity continuous exercise(MCE)and high intensity interval exercise(HIE)on renal fibrosis in spontaneously hypertensive rats(SHR)and the possible mechanism of collagen metabolic pathway(anabolism and catabolism),so as to develop the optimal exercise rehabilitation prescription for patients of hypertensive nephropathy.Methods:Forty-five 3-month-old male SHR were randomly divided into sedentary(SHR-S),MCE(SHR-M)or HIE(SHR-HIE)groups,at mean time,10 Wistar-Kyoto(WKY)were used as normotensive group.Rats of WKY and SHR-R groups kept quietly at cage while those of SHR-M and SHR-H groups performed corresponding mode of exercise intervention for 18 weeks.After experiment,caudal artery blood pressure was measured by non-invasive blood pressure tester;renal function was tested by blood urea nitrogen(BUN),serum creatinine(SCr)and 24 h urine protein;renal histopathological observation was conducted by HE and Masson’s staining to grade renal tubule interstitial injury and interstitial collagen volume fraction(CVF)respectively;protein expression of transforming growth factor-β_(1)(TGF-β_(1)),phosphorylation of Smad2/3(p-Smad2/3),connective tissue growth factor(CTGF),matrix metalloproteinase-9(MMP-9)and tissue inhibitors of metalloproteinase-1(TIMP-1)was tested by Western blot;the expression ofα-smooth muscle actin(α-SMA)was tested through immunohistochemistry.Results:Blood pressure,24 h urine protein,BUN,SCr,renal tubule interstitial injury score,CVF,TGF-β_(1),p-Smad2,p-Smad23,CTGF protein expression,TIMP-1 protein expression and kidneyα-SMA expression were higher(p<0.05),while MMP-9 protein expression and MMP-9/TIMP-1 ratio were lower(p<0.05)in SHR-S group than WKY group;blood pressure,24 h urine protein,BUN,SCr,renal tubule interstitial injury score,CVF,TGF-β_(1),p-Smad2/3,CTGF protein expression,TIMP-1 protein expression and kidneyα-SMA were lower(p<0.05),while MMP-9 protein expression and MMP-9/TIMP-1 ratio were both higher(p<0.05)in SHR-M group than SHR-S group;ren

关 键 词：中等强度持续运动 高强度间歇运动 高血压肾病 肾脏纤维化 细胞外基质 胶原代谢 

分 类 号：G804.5[文化科学—运动人体科学]