Changes Of The Podocyte Silt Diaphragm And Its Mechanism In Rat With Proteinuria Under Intensive Training

Objective: Set up the rat model of exercise-induced sustainable proteinuria under intensive training.Starting from the structural basis of the proteinuria-slit diaphragm,explore the impact of undue exercise stress on kidney structure and ultrastructure of slit diaphragm in rats.With its main constituting protein-Nephrin as the core,explore the mechanism of abnormal slit diaphragm in rats with sustainable exercise-induced proteinuria under overload training period,and explain the relationship between overload training and exercise-induced proteinuria to provide experimental evidence.Methods: Study one,Sprague-Dawley rats are randomly divided into control group(group C),drawn 30 min after training(group EI),drawn 24 h after training(group EA).The rats in the exercise group undergo incremental training for six weeks(grade 10%,6d/w),and they are operated 30 min and 24 h after last training.Detect the urine and serum indexes,and observe the morphology and ultrastructure of kidney.The training plan of study two is same to study one.Observe the apoptosis of renal cells and the apoptotic characteristics of glomerulus podocyte,then detect the mechanism indexes of urine,plasma and kidney.Result:(1)6-week intensive training results in abnormal kidney morphology and ultrastructure of slit diaphragm.The weight of rats in group EI and EA show negative growth at the sixth week.The serum T/C decrease firstly and then increase,but group EI and EA are significantly lower than group C(p<.01,p<.05);The SCr and BUN of group EI and EA are significantly lower than that in group C(p<.01),but only the SCr shows a callback,and group EA are significantly lower than group EI(p<.01);After exercise,UTP and m Alb are maintained at a high level within 24 h,while at 24 h,they decrease.(2)6-week intensive training results in a high level of TNF-? in kidney of rats.Intrarenal and circulating Ra and Ang? increase as the extension of rest time,the changes of intrarenal RAS are more obvious,and the expression of Nephrin continues to be low.(3)After 6-week intensive training,the apoptosis of renal cells in rats increase,and the apoptotic characteristics of foot cells in the glomeruli are obvious;There is no significant change in PI3K/AKT pathway activity.The ratio of Bax/Bcl-2 in group EI and EA are lower than that in group C(p<.01),and the expression of Caspase-3 in group EA is significantly higher than group C and EI(p<.05).Conclusion: The sustainable exercise-induced proteinuria model of rats is established under intensive training,the kidney morphology shows abnormal symptoms,and the changes in the ultrastructure of slit diaphragm are analogous to pathology.Intensive training stimulates the intrarenal and circulating RAS,and the intrarenal RAS is more active.The increase of Ang? decrease the expression of Nephrin within 24 h after exercise;The continuous low expression of Nephrin results in the apoptosis of renal cells,but it may be not accomplished by the downstream PI3K/AKT pathway regulated by Nephrin.