Effects Of Exercise Preconditioning On Autophagy-related Proteins In Cortex Of Ischemic Stroke Model Of Aged Mice

The aim of study:To observe the effect of long-term aerobic exercise preconditioning on the cortex autophagy-related protein,which in aged Ischemic stroke injury model mice,to explore the relationship of exercise preconditioning on cerebral ischemia reperfusion injury and the protective effect of autophagy activation.Methods:80 ICR 60 week old healthy aged mouse were randomly divided into Sham group(Sham)and exercise group(E).The control group did not exercise,the exercise group for 9 weeks of wheel training.After the last training,all the mouse were trained to carry out the test of beam-walking,grip strength and time to exhaution.After 48 h of the time to exhaution,the control group were randomly divided into control group(Sham),middle cerebral artery occlusion model group(M),the animals in the exercise group were randomly divided into exercise+Sham group(E+Sham)and exercise+MCAO group(E+M).To establish the ischemia reperfusion model,M group and E+M group with middle cerebral artery occlusion operation.The animal of Sham group and E+Sham group only neck incision skin,then sutured directly,not to implement the MCAO operation.After 12 h,MCAO model group was evaluated by the neurobehavioral scores.The expression of autophagy/ mitophagy related protein LC3,Atg5,Atg7,Beclin1,BNIP3 L and Parkin in the cortex of the schemic side was determined by the method of Western blot.Results:(1)Exercise preconditioning improved balance ability,grip strength and exercise endurance in aged MCAO mice.The beam-walking results show that compared with the Sham group,the balance time of E group significantly shorter(P<0.01);the grip strength results show thatcompared with Sham group,the maintain time of the group E was increased significantly(P<0.01);time to exhaution results show that compared with the Sham group,the exhaustive time of E group significantly increased(P<0.01).(2)Exercise preconditioning improved neurologica score in aged MCAO miceThe neurological score of E+MCAO group in the aged mice was significantly decreased after MCAO 12h(P<0.01).(3)Effects of exercise preconditioning on the expression of autophagy related protein in the injured cortex of MCAO mice.Compared with the Sham group,LC3-II/LC3-I ratio of E+Sham group was no significant difference,LC3-II/LC3-I ratio of M group was significantly decreased(P<0.01);compared with M group,LC3-II/LC3-I ratio of E+M group was significantly increased(P<0.01);compared with the Sham group,LC3-II/ ?-actin ratio of E+Sham group was significantly decreased(P<0.05),LC3-II/ ?-actin ratio of M group was significantly decreased(P<0.01);compared with M group,LC3-II/?-actin ratio of E+M group was significantly increased(P<0.01).Compared with the Sham group,the expression of Atg5 in the E+Sham group was no significantly decreased(P<0.05),the expression of Atg5 in the M group was significantly decreased(P<0.01);Compared with the M group,the expression of Atg5 in the E+M group was significantly increased(P<0.05).Compared with the Sham group,the expression of Atg7 in the E+Sham group was not significantly difference,the expression of Atg7 in the M group was significantly decreased(P<0.05);compared with the M group,the expression of Atg7 in the E+M group was significantly increased(P<0.05).Compared with the Sham group,the expression of Beclin1 in the E+Sham group was not significantly different,the expression of Beclin1 in the M group was not significantly different,compared with the M group,the expression of Beclin1 in the E+M group was significantly increased(P<0.05).(4)Effects of exercise preconditioning on the expression of mitophagy related protein in the injured cortex of MCAO mice.Compared with the Sham group,the expression of BNIP3 L in E+Sham group was significantly increased(P<0.01),the expression of BNIP3 L in M group was significantly reduced(P<0.05),Compared with M group,the expression of BNIP3 L wassignificantly increased(P<0.01).Compared with the Sham group,the expression of Parkin in E+Sham group was significantly increased(P<0.05),the expression of Parkin in M group was significantly reduced(P<0.05),Compared with M group,the expression of group E+M was significantly increased(P<0.01).Conclusions:Exercise preconditioning has neuroprotective effect on aged ischemic stroke,this effect may be related to the activation of autophagy/mitophagy in the ischemic cortex.