Swimming Exercise Ameliorates Hypertension-Induced Kidney Dysfunction via Alleviating Renal Interstitial Fibrosis and Apoptosis
Swimming Exercise Ameliorates Hypertension-Induced Kidney Dysfunction via Alleviating Renal Interstitial Fibrosis and Apoptosis
复制标题
DOI：
10.1159/000514680
复制
发表时间：
2021-04-01
影响因子：
2.8
通讯作者：
Zhang, Kun-Ru
中科院分区：
文献类型：
--
作者：
Duan, Yong-Chang;Shi, Lin;Zhang, Kun-Ru
背景：高血压肾病是终末期肾病的主要病因之一。运动被认为是高血压及其并发症的非病理性治疗，但其机制尚不清楚。本研究旨在探讨周期性游泳是否能改善高血压所致的肾功能不全及其机制。研究方法：4周龄雄性自发性高血压大鼠（SHR）随机分为高血压组（SHR，n = 8）和运动组（SE，n = 8）。Wistar-Kyoto大鼠（WKY，n = 8）为安静血压正常组。每周记录体重和血压（BP）。在8周的静坐或游泳运动后，测量血脂、BUN和Cr。采用Masson三色染色和苏木精-伊红染色进行肾间质纤维化的组织病理学分析。TUNEL法检测肾细胞凋亡。检测肾皮质组织中负责TGF-β 1/Smad信号传导的关键蛋白，即TGF-β 1、Smad 2/3和Smad 7，以及凋亡相关蛋白Bax和Bcl-2的表达。结果：与SHR相比，8周游泳运动可降低血压和体重，降低BUN和血清Cr浓度。运动可显著抑制高血压引起的肾小管变性、细胞簇集、肾小管细胞肿胀及肾小球变性，减轻肾间质纤维化和肾细胞凋亡。此外，TGF-β 1，Smad 2/3和Bax的表达在SHR中高于WKY，这些表达被运动显著抑制。与此相反，高血压降低Smad 7和Bcl-2的表达增强的游泳运动。肾功能指标、血脂和关键蛋白表达之间存在强相关性。结论：我们的研究结果表明，周期性游泳改善高血压引起的肾功能不全的有益效果，突出了游泳运动作为早期预防高血压引起的肾脏疾病的非病理性治疗的潜力。
Background: Hypertensive nephropathy is one of the major causes of ESRD. Exercise has been considered a nonpathological therapy for hypertension and its complications, yet mechanisms remain unclear. We sought to investigate whether periodic swimming could ameliorate hypertension-induced kidney dysfunction and its underlying mechanisms. Methods: Four-week male spontaneously hypertensive rats (SHRs) were randomly divided into the hypertension group (SHR, n = 8) and exercise group (SE, n = 8, 60 min swimming/day, 6 days per week, for 8 weeks). Wistar-Kyoto rats (WKY, n = 8) were served as a sedentary normotensive group. Bodyweight and blood pressure (BP) were recorded weekly. After 8-week sedentary or swimming exercise, lipids profile, BUN, and Cr were measured. The renal interstitial fibrosis was examined by the histopathological analysis using Masson's trichrome staining and hematoxylin and eosin staining. The kidney cell apoptosis was tested by TUNEL staining. The expressions of critical proteins responsible for the TGF-beta 1/Smad signaling of fibrosis, that is, TGF-beta 1, Smad2/3, and Smad7, as well as apoptosis related proteins, Bax and Bcl-2 in kidney cortex tissues were measured. Results: The 8-week swimming exercise reduced BP and bodyweight, lowered concentrations of BUN, and serum Cr, compared with SHR. Exercise remarkably inhibited hypertension-induced tubular degeneration, cellular cluster, and tubular cell swelling as well as glomerular degeneration in the kidney cortical tissues, attenuated renal interstitial fibrosis, and renal cell apoptosis. Moreover, expressions of TGF-beta 1, Smad2/3, and Bax were higher in the SHR than the WKY, which were significantly suppressed by the exercise. In contrast, hypertension-reduced expressions of Smad7 and Bcl-2 were enhanced by the swimming exercise. Strong correlations were found between kidney function indices, blood lipids, and key protein expressions. Conclusion: Our results demonstrate beneficial effects of the periodic swimming on ameliorating hypertension-induced kidney dysfunction highlighting the potential of swimming exercise as a nonpathological therapy for early prevention of hypertension-caused kidney diseases.