Study On The Effect Of Congrong Shujing Granule On PPAR-γ/PGC-1α Pathway In Parkinson’s Disease Model Rats

ObjectiveTo observe the effect of Congrong Shujing Granules on PPAR-γ/PGC-1α,a pathway in Parkinson’s disease model rats,and to explore the possible mechanism of improving alleviation of mitochondrial damage and behavioral impairment,reducing apoptosis and protecting neurons in rats with Parkinson’s disease,so as to provide an experimental basis for the clinical application of CRSJG and a reference for the improvement and development of Parkinson’s disease diagnosis and treatment strategies.MethodsFifty healthy male SD rats were randomly divided into a normal group of 10 and a model group of 40 and the Parkinson’s disease model was established by subcutaneous injection of rotenone into the back of the neck.After behavioral scorin,the rats with successful modeling were randomly divided into model group,CRSJG group and medopa group,and CRSJG group was gavaged with CRSJG solution,medopa group was gavaged with medopa suspension as a positive control group,and the normal and model groups were gavaged with saline.Behavioral experiments(grid test,slant plate test)were performed on the 14 th day of modeling,7th day and 14 th day of treatment to assess the behavioral changes in each group of rats.After 14 days of treatment,mitochondrial morphological changes were observed by transmission electron microscopy in each group;the expression of PPAR-γ/PGC-1α pathway-related proteins(PPAR-γ、PGC-1α、TFAM、NRF2)and apoptotic factors(Cleaved caspase3、BAX、Bcl-2)were measured by Western blot;the positive expression of TH and α-syn was measured by immunohistochemistry;the apoptosis rate was measured by TUNEL.Results1.Behavioral experimental results: 14 days after the model was established,compared with the normal group,the moving latency of rats in the model group was shortened and the angle of inclined plate tilt was reduced(P<0.05);After 7 days of drug intervention,compared with the normal group,the moving latency of rats in the model group was shortened and the angle of inclined plate tilt was reduced(P<0.05);compared with the model group,the moving latency of the rats in the CRSJG group and medopa group was prolonged(P<0.05),but the difference in the angle of inclined plate tilt was not statistically significant(P>0.05);compared with medopa group,there was no significant difference in the moving latency and the angle of inclined plate tilt in the CRSJG group(P>0.05);14 days after drug intervention,compared with the normal group,the moving latency of rats in the model group was shortened and the angle of inclined plate tilt was reduced(P<0.05);compared with the model group,the CRSJG group and medopa group had a prolonged movement latency and an increase in the tilt angle of the inclined plate(P<0.05);compared with the medopa group,there was no statistically significant difference in the movement latency and the tilt angle of the inclined plate of the rats in the CRSJG group(P>0.05).2.Mitochondrial morphology of rats in each group:compared with the normal group,the mitochondria in the medulla oblongata of rats in the model group were swollen in appearance,the cristae were blurred and disordered,and some of them were broken and vacuolated;compared with the model group,the mitochondrial morphology of rats in the CRSJG group and medopa group was less damaged,the cristae were still clear and neatly arranged,and only a few mitochondria were swollen and vacuolated.3.The expression results of PPAR-γ/PGC-1α pathway-related proteins: after drug intervention:compared with the normal group,the expression of PPAR-γ/PGC-1α pathway related proteins(PPAR-γ,PGC-1α,TFAM,NRF2)in the model group decreased(P<0.05);compared with the model group,the expression of PPAR-γ/PGC-1α pathway related proteins(PPAR-γ,PGC-1α,TFAM,NRF2)was increased in rats of the CRSJG group and medopa group(P<0.05);compared with the medopa group,the expression of PPAR-γ,PGC-1α,TFAM,and NRF2 in the PPAR-γ/PGC-1α pathway of rats in the CRSJG group has no significant difference in the expression(P>0.05).4.TH and α-syn results: after 14 days of drug intervention:compared with the normal group,the positive expression of TH in the substantia nigra of rats in the model group was decreased,and the expression of α-syn in the medulla oblongata was increased(P <0.05);compared with the model group,the positive expression of TH in the substantia nigra of rats in CRSJG group and medopa group was increased,and the expression of α-syn in the medulla oblongata was decreased(P<0.05);compared with the medopa group,there was no significant difference in the positive expression of TH in the substantia nigra and α-syn in medulla oblongata of the CRSJG group(P>0.05).5.Apoptosis results: after 14 days of drug intervention:compared with the normal group,the apoptosis rate,Cleaved caspase3,BAX expression in the medulla oblongata of the model group increased,and the expression of Bcl-2 decreased(P<0.05);compared with the model group,the apoptosis rate,Cleaved caspase3 and BAX expression in the medulla oblongata of the CRSJG group and medopa group were decreased and Bcl-2 expression was increased(P<0.05);compared with the medopa group,the apoptosis rate,and the expression of Cleaved caspase3,BAX,Bcl-2 in the medulla oblongata has no significant difference in rats of CRSJG group(P>0.05).Conclusions1.Congrong Shujing Granules can improve the behavioral dysfunction in Parkinson’s disease rats.2.Congrong Shujing Granules can reduce the destruction of mitochondrial morphology.3.Congrong Shujing Granules may regulate the expression of PPAR-γ/PGC-1α pathway related proteins,increase TH positive expression,reduce α-syn accumulation and apoptosis in PD model rats.