Effects Of Treadmill Exercise On The JNK Signaling Pathway And Angiogenesis In Rat Brain After Cerebral Ischemia

Objects In this study we aimed to explore the mechanisms of treadmill exercise promote angiogenesis through JNK signaling pathway. Observing treadmill exercise effect on the expression of JNK signaling pathway and the related factors of vessel in the rat brain after cerebral ischemia.Methods 1? Male adult health Sprague-dawley(SD) rats which weigh were between 250-280 g were randomly divided into different groups. 1.1? Grouping of time points: rats were randomly divided into 6 groups. Sham group and exercise group in different time point subgroup. n=8. 1.2 ? Grouping after intervention: rats were randomly divided into 5 groups. sham-operated group, MCAO group, exercise group,control group,inhibitor group. n=12. 2?the MCAO model was made by modified Zea-longa's method. 3?All of the rats received 3 day's adaptive treadmill exercise before operation. 24 hours after MCAO, all of them start to exercise except sham group and MCAO group. sham group and MCAO group were arranged at the instrument of treadmill exercise, but the speed was 0 m/min.Each group lasted 30 minutes. 4?The brain tissues from E group was collected at the following time points, such as 3d, 7d, 14 d, 21 d, 28 d. The western blot was used to test the expression of the factors of JNK signaling pathway at different time points. 5?Since 7th days after MCAO, M+E+SP group received SP600125 which is JNK inhibitor by gavage and M+E+C group received PPCES which is solvent of the inhibitor by gavage. All of the two groups lasted the administration 7 days. 6?modified neurological severity score(m NSS) and modified adhesive removal testwere performed at 1, 3, 7, 14 days after MCAO to evaluate the changes of neural function in each groups. 7?Collection the brain tissues at 14 th days.The western blot was used to test the expression of v WF, VEGF and the factors of JNK signaling pathway. The immunofluorescence was used to detect the expression of VEGF at the peri-infarct cortex.Results 1?The expression of the factors of JNK signaling pathway of E group reach the peak at third day. They slowly increase again after decrease from the peak. They reach another peak between 14 th to 21 th day. Then decrease again. 2?Treadmill exercise may promote the recovery of neural function after MCAO and the angiogenesis at the peri-infarct cortex. The m NSS score of exercise group is lower than the MCAO. The modified adhesive removal test's result is lower too. The exercise could promote the expression of JNK signaling pathway,also benefit for the expression of VEGF and v WF at the peri-infarct cortex. 3?SP600125, JNK inhibitor, could significantly inhibit the expression of VEGF and v WF at the peri-infarct cortex.Conclusions Treadmill exercise could promote the recovery of neural function. The underling mechanisms maybe that treadmill exercise activated the JNK signaling pathway, then promote the expression of VEGF and get the effect of promoting angiogenesis.