Elucidation of the mechanism that therapeutic exercise effectively inhibits the aggravation of progressive renal disease in diabetes mellitus.

评估慢性运动（EX）对糖尿病肾病（DN）模型大鼠肾脏的影响，以及EX和血管紧张素II型1受体拮抗剂氯沙坦（LOS）联合使用的益处。半肾切除的Goto-Kakizaki大鼠被喂食高热量饮食，并自由获得30%蔗糖溶液以发展DN。将大鼠分为4组：1)无EX (C)；2)跑步机EX（20米/分钟，60分钟/天，5天/周）；3)洛(5毫克/公斤/天);4) EX+LOS，治疗12周。实验结束时，切除残余肾脏，进行组织病理学分析，并使用ED-1、α -平滑肌肌动蛋白（SMA）和Wilms' tumor (WT)-1抗体进行免疫组织学分析。LOS组和EX+LOS组的收缩压（SBP）明显低于C组和EX组。EX、EX+LOS和LOS可减弱蛋白尿的增加。EX组、EX+LOS组和LOS组大鼠肾小球硬化指数（glomerular sclerosis， IGS）和肾皮质相对间质体积均较C组显著改善。其中，EX+LOS组大鼠肾小球中ED-1和α - sma表达最少，WT-1阳性细胞数最多。EX组和EX+LOS组的耐力跑能力显著强于LOS组和C组。这些结果表明，EX和LOS具有肾保护作用，而EX的作用与收缩压降低无关。这些结果也提示EX和LOS同时治疗比LOS单独治疗具有更大的肾保护作用，并可能影响DN模型大鼠巨噬细胞浸润、系膜激活和足细胞损失。他们还认为，在这种大鼠模型中，EX具有增强耐力而无肾脏并发症的作用。

To assess the renal effects of chronic exercise (EX) in a rat model of diabetic nephropathy (DN) and the benefits of combined EX and angiotensin II type-1 receptor antagonist, losartan (LOS).Heminephrectomized Goto-Kakizaki rats were fed a high-caloric diet and had free access to 30% sucrose solution to develop DN. The rats were divided into 4 groups: 1) no EX (C); 2) EX with treadmill running (20m/min, 60min/day, 5days/week); 3) LOS(5mg/kg/day); 4) EX+LOS, and the rats were treated for 12 weeks. At the end of the experiment, remnant kidneys were removed, and were analyzed for histopathology, and for immunohistologically using antibodies against ED-1, alpha-smooth muscle actin (SMA) and Wilms' tumor (WT)-1.Systolic blood pressure (SBP) in the LOS and EX+LOS groups was significantly lower than that in the C and EX groups. EX, EX+LOS and LOS blunted increases in proteinuria. The index of glomerular sclerosis (IGS) and the relative interstitial volume of the renal cortex were significantly improved in the EX, EX+LOS and LOS groups than those in the C group. Particularly, the IGS, the expressions of ED-1 and alpha-SMA in the glomerulus were the lowest, and the number of WT-1 positive cells was the highest in the EX+LOS group. The ability of endurance running in the EX and EX+LOS groups was significantly stronger than that in the LOS and C groups.These results suggested that EX and LOS have renoprotective effects, and that the effects of EX were not related to the SBP reduction. These results also suggested that the simultaneous treatment with EX and LOS provided greater renoprotective effect than that of LOS alone and may affect the macrophage infiltration, the mesangial activation, and the podocyte loss in this rat model of DN. They also suggested that EX has the effect which enhances endurance without renal complications in this rat model.