摘要
背景:2型糖尿病常伴随肾功能障碍,现已有大量研究表明运动能够缓解糖尿病患者代谢紊乱及肾功能损伤。但是关于运动对2型糖尿病患者肾脏保护作用的具体机制,鲜有人报道。目的:探讨有氧运动是否通过抑制转化生长因子β1/Notch1通路改善2型糖尿病大鼠肾功能。方法:将雄性SD大鼠随机分为正常对照组和糖尿病模型组,造模成功后再随机分为糖尿病对照组和糖尿病运动组,糖尿病运动组进行8周有氧运动干预。运动结束后取材,采用全自动生化分析仪和ELISA法检测糖脂代谢、肾功能相关指标;通过电镜观察肾皮质细微结构改变;采用ELISA和RT-PCR技术检测大鼠肾脏组织中相关蛋白和基因表达量。结果与结论:①相较于正常对照组,糖尿病对照组大鼠空腹血糖、总胆固醇、三酰甘油水平及胰岛素抵抗指数显著增加(P<0.05);有氧运动能够显著降低空腹血糖、三酰甘油水平(P<0.05);②相较于正常对照组,糖尿病对照组大鼠尿微量白蛋白、血清尿素氮和血清肌酐水平极显著增加(P<0.01),肾脏基底膜增厚,系膜基质增生,伴一定程度的足突融合,肾脏病变明显;有氧运动能够极显著下调2型糖尿病大鼠尿微量白蛋白、血清尿素氮和血清肌酐的过表达(P<0.01),明显改善糖尿病大鼠肾脏的病理改变;③相较于正常对照组,糖尿病对照组大鼠肾组织转化生长因子β1、Notch1、Jagged1、Hes1蛋白和基因表达量均极显著增加(P<0.01);有氧运动对转化生长因子β1、Notch1及Jagged1蛋白和基因的过表达有极显著的抑制作用(P<0.01),同时也可以显著性地抑制Hes1蛋白的过表达(P<0.05);④综上可知,有氧运动可以保护糖尿病大鼠肾功能,延缓肾的病理进展,这可能是通过抑制转化生长因子β1/Notch1信号通路的过度表达来实现的。
BACKGROUND:Type 2 diabetes is often accompanied by renal dysfunction.Increasing studies have shown that exercise can alleviate metabolic disorders and renal dysfunction in diabetic patients.However,the specific mechanism underlying the renal protective effect of exercise in patients with type 2 diabetes is rarely reported.OBJECTIVE:To investigate whether aerobic exercise can improve renal function in type 2 diabetic rats by inhibiting transforming growth factorβ1/Notch1 pathway.METHODS:Male Sprague-Dawley rats were randomly divided into normal control group and diabetes model group.After successful modeling,they were randomly divided into diabetes control group and diabetes exercise group.Rats in the diabetes exercise group were subjected to an 8-week aerobic exercise.Samples were collected after exercise,and the relevant indexes of glucose and lipid metabolism and renal function were detected by automatic biochemical analyzer and ELISA.The microscopic structure of renal cortex was observed by electron microscope.ELISA and RT-PCR were used to detect the expression of related proteins and genes in rat kidney tissue.RESULTS AND CONCLUSION:Compared with the normal control group,fasting blood glucose,total cholesterol,and triglyceride levels and insulin resistance index were significantly increased in the diabetic control group(P<0.05).Aerobic exercise could significantly reduce fasting blood glucose and triglyceride levels(P<0.05).Compared with the normal control group,the diabetic control group had significantly increased contents of urinary microalbumin,serum urea nitrogen and serum creatinine(P<0.01),thickened renal basement membrane,mesangial matrix hyperplasia,accompanied by a certain degree of foot process fusion,and obvious lesion of the kidney.Aerobic exercise could significantly down-regulate the overexpressions of urinary microalbumin,serum urea nitrogen and serum creatinine in type 2 diabetic rats(P<0.01),and significantly improve the pathological changes of the kidney in diabetic rats.Compared with the normal control group,the protein and gene expression levels of transforming growth factorβ1,Notch1,Jagged1 and Hes1 in rat kidney tissue were significantly increased in the diabetic control group(P<0.01).Aerobic exercise had a highly significant inhibitory effect on the overexpression of transforming growth factorβ1,Notch1 and Jagged1 proteins and genes(P<0.01)and also significantly inhibited the overexpression of Hes1 protein(P<0.05).In conclusion,aerobic exercise can protect renal function and delay the pathological progression of the kidney in diabetic rats,which may be achieved by inhibiting the overexpression of transforming growth factorβ1/Notch1 signaling pathway.
作者
吴玉珍
孙青
刘霞
周雨
金其贯
Wu Yuzhen;Sun Qing;Liu Xia;Zhou Yu;Jin Qiguan(Hunan Provincial Key Laboratory of Physical Fitness and Sports Rehabilitation,Physical Education College of Hunan Normal University,Changsha 410012,Hunan Province,China;Physical Education College of Yangzhou University,Yangzhou 225127,Jiangsu Province,China)
出处
《中国组织工程研究》
CAS
北大核心
2024年第14期2145-2151,共7页
Chinese Journal of Tissue Engineering Research
基金
湖南省大学生创新训练计划项目(S202210542163),项目负责人:周雨
长沙市自然科学基金项目(kq2208166),项目负责人:刘霞
国家社会科学基金项目(22BTY103),项目负责人:刘霞。
