节点文献
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
【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β1(TGF-β1)、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-β1、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-β1、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-β1、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-β1、p-Smad2、pSmad3、CTGF蛋白表达量、肾脏α-SMA表达量均高于SHR-M组(p<0.05),而MMP-9蛋白表达量、TIMP-1蛋白表达量和MMP-9/TIMP-1比值均低于SHR-M组(p<0.05)。结论:长期中等强度持续运动通过维持胶原代谢稳态(即促进降解并降低合成)及抑制成纤维细胞向成肌纤维细胞分化而减轻自发性高血压大鼠肾脏纤维化并改善肾功能;长期高强度间歇运动则进一步破坏胶原稳态平衡(抑制胶原降解,但对胶原合成无影响)加重自发性高血压大鼠肾脏纤维化,但并未引起成纤维细胞转化及肾功能继续恶化。因此,中等强度持续运动仍然是高血压肾病患者康复的最佳运动方式,长期高强度间歇运动对高血压肾病患者的安全性和有效性有待进一步研究。
【Abstract】 To 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-β1(TGF-β1),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-β1, p-Smad2, p-Smad23, CTGF protein expression, TIMP-1 protein expression and kidney α-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-β1, p-Smad2/3,CTGF protein expression, TIMP-1 protein expression and kidney α-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;renal tubule interstitial injury score and CVF were both higher(p<0.05) than SHR-S group, but blood pressure,renal function, protein of TGF-β1, p-Smad2, p-Smad3, CTGF protein expression and kidney α-SMA were no significantly different(p>0.05) in SHR-H group; blood pressure, renal function, renal tubule interstitial injury score, CVF, TGF-β1, p-Smad2, p-Smad3 and kidney α-SMA expression were higher(p<0.05), while MMP-9 protein expression, TIMP-1 protein expression and MMP-9/TIMP-1 ratio were lower(p<0.05) in SHR-H group than SHR-M group. Conclusions: Long-term MCE alleviated renal fibrosis of SHR through maintenance of collagen metabolism homeostasis(promoted degradation and reduced synthesis) as well as inhibition of differentiation of fibroblasts into myofibroblasts; however, long-term HIE exacerbated renal fibrosis in spontaneously hypertensive rats by further destruction of collagen homeostasis(suppressed collagen degradation, but had no effect on collagen synthesis) but failed to induce phenotype transformation of fibroblasts and subsequent renal dysfunction. Therefore, MCE is still the optimal exercise rehabilitation modality for patients of hypertensive nephropathy, although the safety and efficacy of long-term HIE to patients with hypertensive nephropathy should be further confirmed.
【Key words】 moderate-intensity continuous exercise; high-intensity interval exercise; hypertensive nephropathy; renal fibrosis; extracellular matrix; collagen metabolism;
- 【文献出处】 首都体育学院学报 ,Journal of Capital University of Physical Education and Sports , 编辑部邮箱 ,2021年06期
- 【分类号】R692;G804.2
- 【下载频次】27.00000