Chronic Running Exercise Alleviates Early Progression of Nephropathy with Upregulation of Nitric Oxide Synthases and Suppression of Glycation in Zucker Diabetic Rats.
Chronic Running Exercise Alleviates Early Progression of Nephropathy with Upregulation of Nitric Oxide Synthases and Suppression of Glycation in Zucker Diabetic Rats.
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DOI：
10.1371/journal.pone.0138037
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Kiyomoto H
中科院分区：
文献类型：
--
作者：
Ito D;Cao P;Kakihana T;Sato E;Suda C;Muroya Y;Ogawa Y;Hu G;Ishii T;Ito O;Kohzuki M;Kiyomoto H
众所周知，运动训练对2型糖尿病和肥胖症患者具有多种有益作用，包括肾脏保护。然而，调控这些行为的机制尚不清楚。本研究评估了慢性跑步运动对早期糖尿病肾病的影响，重点研究了Zucker糖尿病脂肪（ZDF）大鼠肾脏的一氧化氮合酶（NOS）、氧化应激和糖基化。雄性ZDF大鼠（6周龄）进行8周的强制跑步机运动（前ZDF）。久坐ZDF （Sed-ZDF）和Zucker lean （Sed-ZL）大鼠作为对照。运动减轻了ZDF大鼠的高血糖（血浆葡萄糖；Sed-ZDF 242±43 mg/dL, Ex-ZDF 115±5 mg/dL），增加了胰岛素分泌（血浆胰岛素；2.3±0.7和5.3±0.9 ng/mL），减少了白蛋白排泄（尿白蛋白；492±70和176±11 mg/g肌酐）和正常的肌酐清除率（9.7±1.4和4.5±0.8 mL/min /体重）。sd - zdf大鼠肾脏内皮细胞(e)和神经元细胞(n) NOS表达低于sd - zl大鼠（p<0.01），运动使eNOS和nNOS表达上调（p<0.01）。此外，运动降低了ZDF大鼠肾脏NADPH氧化酶活性、p47phox表达（p<0.01）和α-氧醛（晚期糖基化终产物的前体）（p<0.01）。此外，形态计量学证据表明，运动后肾脏损伤减少。这些数据表明，运动对糖尿病肾病早期发展的ZDF大鼠肾脏的保护作用，至少在一定程度上，是通过上调肾脏NOS表达、抑制NADPH氧化酶和α-氧醛的作用。此外，本研究支持慢性有氧运动可以作为一种有效的非药物治疗方法推荐用于2型糖尿病和肥胖症早期的肾保护。
Exercise training is known to exert multiple beneficial effects including renal protection in type 2 diabetes mellitus and obesity. However, the mechanisms regulating these actions remain unclear. The present study evaluated the effects of chronic running exercise on the early stage of diabetic nephropathy, focusing on nitric oxide synthase (NOS), oxidative stress and glycation in the kidneys of Zucker diabetic fatty (ZDF) rats. Male ZDF rats (6 weeks old) underwent forced treadmill exercise for 8 weeks (Ex-ZDF). Sedentary ZDF (Sed-ZDF) and Zucker lean (Sed-ZL) rats served as controls. Exercise attenuated hyperglycemia (plasma glucose; 242 ± 43 mg/dL in Sed-ZDF and 115 ± 5 mg/dL in Ex-ZDF) with increased insulin secretion (plasma insulin; 2.3 ± 0.7 and 5.3 ± 0.9 ng/mL), reduced albumin excretion (urine albumin; 492 ± 70 and 176 ± 11 mg/g creatinine) and normalized creatinine clearance (9.7 ± 1.4 and 4.5 ± 0.8 mL/min per body weight) in ZDF rats. Endothelial (e) and neuronal (n) NOS expression in kidneys of Sed-ZDF rats were lower compared with Sed-ZL rats (p<0.01), while both eNOS and nNOS expression were upregulated by exercise (p<0.01). Furthermore, exercise decreased NADPH oxidase activity, p47phox expression (p<0.01) and α-oxoaldehydes (the precursors for advanced glycation end products) (p<0.01) in the kidneys of ZDF rats. Additionally, morphometric evidence indicated renal damage was reduced in response to exercise. These data suggest that upregulation of NOS expression, suppression of NADPH oxidase and α-oxoaldehydes in the kidneys may, at least in part, contribute to the renal protective effects of exercise in the early progression of diabetic nephropathy in ZDF rats. Moreover, this study supports the theory that chronic aerobic exercise could be recommended as an effective non-pharmacological therapy for renoprotection in the early stages of type 2 diabetes mellitus and obesity.