运动可能通过下调肾脏Notch-1信号改善Ⅱ型糖尿病大鼠肾功能

Aerobic Swimming Exercise can Improve Renal Function for Type 2 Diabetes Rats through Downregulating the Activity of Notch-1Signaling

目的:观察有氧游泳运动对Ⅱ型糖尿病大鼠肾脏损伤的改善效果,并探讨其可能的机制。方法:45只4周龄健康雄性SD大鼠,随机抽取10只为正常对照组,基础饲料喂养;其余35只经高糖高脂喂养5周后,配合腹腔注射STZ(35 mg/kg.bw)诱导建立Ⅱ型糖尿病大鼠模型;7周后,将成模大鼠随机分为糖尿病安静组和糖尿病运动组,每组14只。3组大鼠均采用基础饲料喂养;糖尿病运动组大鼠进行8周有氧游泳运动;正常对照组、糖尿病安静组2组大鼠均自由活动,不施加任何干预。结果:(1)8周有氧游泳运动后,糖尿病运动组肾脏在电镜下的形态表现为肾小球三层结构较清晰,基底膜增厚不明显,足突融合减少,溶酶体增多现象等均有一定程度减少,较糖尿病安静组有明显改善;(2)糖尿病运动组血糖浓度和24 h UA排泄量较糖尿病安静组显著降低(分别为P<0.05或P<0.01);(3)糖尿病运动组肾皮质Jagged-1、Val1744NICD和Hes-1蛋白的表达较糖尿病安静组均显著降低(P<0.05或P<0.01)。结论:运动可提高Ⅱ型糖尿病大鼠肾功能,改善大鼠肾脏损伤,可能与其下调Ⅱ型糖尿病状态下激活的Notch-1信号通路有关。

Objective ： To investigate the effect of aerobic swimming exercise on improving renal injury in type 2 diabetic rats and its mechanism. Methods ： Forty-five male Spragne-Dawley （SD） rats for 4 weeks were randomly selected 10 SD rats as normal control group by normal diet feeding. The model of type 2 diabetic rats was duplicated in the study through 35 SD rats fed high-sugar-fat diet for five weeks together with intraperitoneal infecting of low dose of STZ （35mg/kg.bw）. After 7 weeks the model rats were randomly divided into diabetic control group （N=14） and diabetic exercise group （N=14）. The three groups were all fed by normal diet feeding. Diabetic exercise group was underwent the intervention of swimming exercise for 8 weeks, while normal control group and diabetic control group moved freely without any intervention. Results： （1）After swimming exercise for 8 weeks, the group treated by exercise could be found through electron microscope that it had clearer glomerular structure, such as no-obvious thickened glomerular basement membrane, decreased fusion of foot process, and reduced lysosome of renal tubular cells, and so on, which improved significantly comparing with diabetic control group. （2） Compared with dia- betic control group, the concentrations of blood glucose and the 24h mieroalbuminuria excretion in diabetic exercise group decreased significantly （P〈0.05 or P〈0.01）. （3） Compared with diabetic control group, diabetic exercise group of Jagged-1 and Val1744NICD and Hes-1 expressions in the renal cortex de- creased significantly （P〈0.05 or P〈0.01 ）. Conclusions： Exercise can protect renal function and improve renal injury for type 2 diabetes, which may be relat- ed to downregulating the activity of Notch- 1 signaling stimulated under type 2 diabetes conditions.