The Function Of PI3K/Akt Signaling Pathway In Over-training Induced Acute Kidney Injury And The Effect Of Anisodamine In Rats

Objective:Over training is a kind of pathological state due to excessive exercise which overloads the body's endurance,leading to multiple organ dysfunctions.Currently,in some parts of the troops,the training methods are still unscientific and some soldiers unilaterally pursue greater amount of exercise.Therefore,over training is a common sport disease at present.Kidney is a hypertransfusion organ and sensitive to hypoxia-ischemia.In the condition of over training,the blood is distributed more to the muscle,lung and heart.The blood flow of kidney decreases obviously and the kidney is vulnerable.Now the morbidity of over training induced acute kidney injury(OTIAKI)is growing year by year and there is no specific treatment so far.Anisodamine is a kind of anticholinergic agent extracted from Anisodus Tanguticus.The studies of our research group show that anisodamine intervention could ameliorate AKT effectively,but its mechanism has not been elucidated completely.Phosphatidylinositol-3-kinase(PI3K)/v.akt murine thymoma viral oncogene homolog(Akt)is an important signal transduction pathway in eukaryocyte and related to various biological activities such as apoptosis,multiplication and differentiation.In recent years,studies show that PI3K/Akt pathway has close relation to multiple acute kidney diseases,which indicates that it may also participate in the pathological change of OTIAKI.In this research we plan to establish the overtraining model of rats by exhausted swimming exercise,and then apply the intervention of anisodamine and PI3K inhibitor,in order to investigate the effect and mechanism of PI3K/Akt signaling pathway in over-training induced acute kidney injury,and whether anisodamine protects the injured kidney via PI3K/Akt signaling pathway.Methods:60 Wistar rats were randomly divided into four groups:normal control group(NC),over-training group(OT),over-training and anisodamine group(OTA),over-training and wortmannin group(OTW).Over-training models were created by one-time exhaustive swimming.OTA and OTW group were respectively given wortmannin 25?l/kg and anisodamine 10mg/kg by intraperitoneal injection.Serum creatinine(Cr),urea nitrogen(BUN)and creatine kinase were measured with autobiochemical analyzer.The renal pathological changes were observed by HE staining.The expressions of Akt,p-Akt and Nrf2 were examined by western blot.The percentage of apoptosis cells'was detected by TUNEL.Results:Compared with the NC group,parts of the Cr,BUN,CK,the kidney damage score,the percentage of apoptosis cells and the Akt and Nrf2 expression of OT group increased significantly(p<0.05).Compared with the OT group,parts of the Cr,BUN,CK,the kidney damage score,the percentage of apoptosis cells of OTA group increased further(p<0.05).Parts of the p-Akt and Nrf2 expressions of OTA group were significantly higher than OT group.The manifestations of OTW group are generally contrary to OTA group(p<0.05).There was no significant difference of Akt expressions among each group.Conclusion:In over-training induced acute kidney injury,PI3K/Akt signaling pathway could be activated increasingly and then inhibit peroxidation and alleviate renal injury.Anisodamine plays a protective role by activating this signaling pathway.