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在慢性肾病啮齿动物模型中,自愿进行4周轮转跑步后心脏功能得以保留。

Cardiac function is preserved following 4 weeks of voluntary wheel running in a rodent model of chronic kidney disease.

作者信息

Kuczmarski James M, Martens Christopher R, Kim Jahyun, Lennon-Edwards Shannon L, Edwards David G

机构信息

Department of Kinesiology and Applied Physiology, University of Delaware, Newark, Delaware; Department of Biological Sciences, University of Delaware, Newark, Delaware.

Department of Kinesiology and Applied Physiology, University of Delaware, Newark, Delaware;

出版信息

J Appl Physiol (1985). 2014 Sep 1;117(5):482-91. doi: 10.1152/japplphysiol.00344.2014. Epub 2014 Jul 24.

Abstract

The purpose of this investigation was to determine the effect of 4 wk of voluntary wheel running on cardiac performance in the 5/6 ablation-infarction (AI) rat model of chronic kidney disease (CKD). We hypothesized that voluntary wheel running would be effective in preserving cardiac function in AI. Male Sprague-Dawley rats were divided into three study groups: 1) sham, sedentary nondiseased control; 2) AI-SED, sedentary AI; and 3) AI-WR, wheel-running AI. Animals were maintained over a total period of 8 wk following AI and sham surgery. The 8-wk period included 4 wk of disease development followed by a 4-wk voluntary wheel-running intervention/sedentary control period. Cardiac performance was assessed using an isolated working heart preparation. Left ventricular (LV) tissue was used for biochemical tissue analysis. In addition, soleus muscle citrate synthase activity was measured. AI-WR rats performed a low volume of exercise, running an average of 13 ± 2 km, which resulted in citrate synthase activity not different from that in sham animals. Isolated AI-SED hearts demonstrated impaired cardiac performance at baseline and in response to preload/afterload manipulations. Conversely, cardiac function was preserved in AI-WR vs. sham hearts. LV nitrite + nitrate and expression of LV nitric oxide (NO) synthase isoforms 2 and 3 in AI-WR were not different from those of sham rats. In addition, LV H2O2 in AI-WR was similar to that of sham and associated with increased expression of LV superoxide-dismutase-2 and glutathione peroxidase-1/2. The findings of the current study suggest that a low-volume exercise intervention is sufficient to maintain cardiac performance in rats with CKD, potentially through a mechanism related to improved redox homeostasis and increased NO.

摘要

本研究的目的是确定在慢性肾脏病(CKD)的5/6肾切除梗死(AI)大鼠模型中,4周的自愿轮转运动对心脏功能的影响。我们假设自愿轮转运动对保留AI大鼠的心脏功能有效。雄性Sprague-Dawley大鼠被分为三个研究组:1)假手术组,久坐不动的非患病对照;2)AI-SED组,久坐不动的AI大鼠;3)AI-WR组,进行轮转运动的AI大鼠。在AI和假手术之后,动物被饲养8周。这8周包括4周的疾病发展期,随后是4周的自愿轮转运动干预/久坐不动对照期。使用离体工作心脏标本评估心脏功能。左心室(LV)组织用于生化组织分析。此外,测量比目鱼肌柠檬酸合酶活性。AI-WR组大鼠的运动量较低,平均跑了13±2公里,这导致其柠檬酸合酶活性与假手术组动物无差异。离体的AI-SED组心脏在基线时以及对前负荷/后负荷操作的反应中表现出心脏功能受损。相反,与假手术组心脏相比,AI-WR组心脏功能得以保留。AI-WR组大鼠左心室亚硝酸盐+硝酸盐以及左心室一氧化氮(NO)合酶同工型2和3的表达与假手术组大鼠无差异。此外,AI-WR组大鼠左心室过氧化氢水平与假手术组相似,并与左心室超氧化物歧化酶-2和谷胱甘肽过氧化物酶-1/2表达增加相关。本研究结果表明,低运动量的运动干预足以维持CKD大鼠的心脏功能,其潜在机制可能与改善氧化还原稳态和增加NO有关。

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