| Objective: Apoptosis is closely related to skeletal muscle motor dysfunction in patients with Parkinson's disease.In this article,the effects of aerobic exercise on motor dysfunction of PD patients and its mechanism are explored by observing the effects of pre-aerobic aerobic exercise training combined with ALDH2 agonist on skeletal muscle cell apoptosis in PD rats,in order to provide theoretical basis for exercise prevention and improvement of motor dysfunction in PD.Methods: 80 3-month-old SPF strong male SD rats were randomly divided into six groups:(1)sedentary-control group(SED,n=12);(2)Parkinson-sedentary control group(SED-PD,n=12);(3)ALDH2-agonistParkinson-sedentary group(AG-SED-PD,n=16);(4)exercise-control group(EX,n=12);(5)Parkinson-exercise control group(EX-PD,n=12);(6)ALDH2-agonist-Parkinson-exercise control group(AG-EX-PD,n=16).After 8 weeks of aerobic treadmill training,and then 6-OHDA-induced PD lesion models were established in each PD group.The control group was injected with normal saline in the same manner and dose.The rats in the agonist group were injected intraperitoneally with ALDH2 agonist 12 hours before and after the modeling,and the control group was injected with normal saline in the same manner and dose.Twenty-four hours after the last training,the gastrocnemius muscle tissues of each group were taken,and the morphological changes of gastrocnemius muscle were observed by HE staining;the gastrocnemius muscle cell apoptosis was observed by TUNEL;the expressions of ALDH2,JNK,P53,Bcl-2,and Bax were measured by IHC.Results:(1)The results of rotation experiments showed that the success rate of modeling in the SED-PD group was 77.78%;the EX-PD group was 71.43%;the AG-SED-PD group was 76.92%;the AG-EX-PD group was 69.23%.(2)During the experiment,the weight of the rats in the quiet group of each group was significantly higher than that in the exercise group(P <0.01),and the changes became more and more obvious with the passage of time.(3)The results of HE staining showed that the skeletal muscle fibers of the normal group were neatly arranged and the number of nuclei was large.In the PD group,the muscle fibers were arranged disorderly,with larger gaps and fewer nuclei and significant improvement after aerobic exercise intervention.Muscle fiber condition can also be improved after agonist administration.(4)TUNEL results showed that apoptotic cells were found in skeletal muscle of each group.Compared with the SED group,the apoptotic cells in PD group increased significantly(P<0.01),and the aerobic exercise intervention group decreased significantly(P<0.05).Apoptosis of skeletal muscle cells in PD rats was also significantly improved after ALDH2-agonist administration(P <0.01).(5)IHC results showed that compared with the SED group,the expression of ALDH2 in the skeletal muscle of the SED-PD group was significantly decreased(P<0.01),the expression of JNK was obviously increased(P<0.05),and the expression of P53 was obviously increased(P<0.01),Bax expression increased significantly(P<0.01),Bcl-2 expression significantly decreased(P<0.01),Bcl-2/Bax ratio decreased significantly(P<0.01);Compared with SED,ALDH2 expression in skeletal muscle of EX group rats increased obviously(P<0.05),and JNK expression decreased(P>0.05),P53 expression decreased(P>0.05),Bax expression decreased slightly(P> 0.05),Bcl-2 expression increased(P<0.05),Bcl-2/Bax ratio rised(P>0.05);Compared with the SED-PD group,the expression of ALDH2 in the skeletal muscle of rats in the EX-PD group increased significantly(P<0.05),the expression of JNK decreased slightly(P>0.05),the expression of P53 decreased significantly(P<0.01),the expression of Bax decreased(P <0.05),and the expression of Bcl-2 significantly increased(P<0.05),Bcl-2/Bax ratio increased significantly(P<0.05);Compared with the SED-PD group,the expression of ALDH2 in the skeletal muscle of the AG-SED-PD group increased significantly(P<0.05),and the expression of JNK decreased obviously(P<0.05),the expression of P53 decreased obviously(P<0.01),the expression of Bax decreased significantly(P<0.05),and the expression of Bcl-2 increased obviously(P<0.05),Bcl-2/Bax ratio increased obviously(P<0.05);Compared to the EX-PD group,the skeletal muscle of the AG-EX-PD group rats ALDH2 expression increased(P>0.05),JNK expression decreased significantly(P<0.01),P53 expression decreased(P>0.05),Bax expression decreased significantly(P<0.05),and Bcl-2 expression increased slightly(P>0.05),Bcl-2/Bax ratio increased significantly(P<0.05);Compared with the AG-SED-PD group,the expression of ALDH2 in the skeletal muscle of the AG-EX-PD group increased slightly(P>0.05),the expression of JNK decreased significantly(P<0.01),and the expression of P53 decreased obviously(P<0.05),Bax expression decreased(P>0.05),and Bcl-2 expression rised(P <0.05),Bcl-2/Bax ratio increased slightly(P>0.05).Conclusions:(1)Apoptosis occurs in the skeletal muscle tissue of rats in each group,but excessive apoptosis of skeletal muscle cells in PD rats may be related to motor dysfunction in PD patients.(2)Regardless of normal rats or PD rats,aerobic exercise can increase the expression of ALDH2 in their skeletal muscles;aerobic exercise combined with ALDH2 agonist Alda-1 can significantly increase the expression of ALDH2 in skeletal muscles of PD rats.(3)Aerobic exercise training can significantly improve the excessive apoptosis of skeletal muscle cells in PD rats,which may be one of the reasons for aerobic exercise to prevent and improve the decline in exercise capacity of PD patients after illness. |
PDF Full Text Request