| Objectives To observe the effects of Congrong Shujing Granule on the stress-related proteins,neurotrophic factor CDNF and JNK signaling pathways in substantia nigra of rats with rotenone-induced PD,and to explore the possible mechanism of neuroprotective effects of Congrong Shujing Granule on PD model rats.Methods PD model rats were prepared with rotenone sunflower oil emulsion(1.5 mg/kg/d).The successful rats were randomly divided into model group,solvent group and low,medium and high dose groups of Congrong Shujing Granules.The rats in solvent group were injected with sunflower oil of equal volume.The normal group was not treated with any treatment.The low,middle and high dose groups were given low,medium and high dose(5.88 g/kg,11.76 g/kg,23.52 g/kg)of Congrong Shujing granule Decoction by gavage for 14 days,and the normal group and solvent group were given the same volume of physiological saline.Behavioral observation was carried out after model establishment and 14 days after drug intervention;expression of TH,CDNF and GRP78 in substantia nigra of rats was detected by immunohistochemistry;expression of CDNF,alpha-syn,GRP78 and JNK pathway-related proteins in substantia nigra of rats was detected by WB;expression of CDNF,alpha-syn and GRP78 genes in substantia nigra of rats was detected by RT-PCR.Results1 Behavioral test results1.1 Suspension test:After the 14 th day of model establishment,compared with the normal group,the scores of model group and administration group decreased significantly(P < 0.01);after the 14 th day of administration,the scores of medium and high dose groups increased compared with model group(P < 0.05 or P < 0.01).1.3 Step test: After the 14 th day of model establishment,compared with the normal group,the stride length of the model group and the administration group decreased significantly(P <0.01);after the 14 th day of administration,the stride length of the medium and high dose groups increased significantly compared with the model group(P < 0.01).2 Changes of TH,GRP78 and CDNF staining2.1 TH:After 14 days of administration,TH expression in the model group was significantly decreased compared with the normal group(P < 0.01);compared with the model group,TH expression in the administration group was significantly increased(P < 0.01).2.2 GRP78 and CDNF: After 14 days of administration,compared the normal group,the expression of GRP78 and CDNF in the model group decreased significantly(P < 0.01);compared with the model group,the expression of GRP78 and CDNF in the medium and high dose groups increased(P < 0.05 or P < 0.01).3.1 alpha-syn:After 14 days of administration,the expression of alpha-syn protein in model group was significantly higher than that in normal group(P < 0.01);compared with model group,the expression of alpha-syn in medium and high dose group was significantly lower(P< 0.01).3 Changes of related protein expression in rats of each group3.2 GRP78 and CDNF: After 14 days of administration,compared with the normal group,the expression of GRP78 and CDNF in the model group increased significantly(P < 0.01);compared with the model group,the expression of GRP78 in the medium and high dose groups increased significantly(P < 0.01),and the expression of CDNF in the administration group increased significantly(P < 0.05).3.3 JNK signaling pathway: After 14 days of administration,the expression of JNK and c-JUN phosphorylated protein in model group increased significantly compared with normal group(P < 0.01);compared with model group,the expression of JNK and c-JUN phosphorylated protein in the administration group decreased significantly(P < 0.01).However,there was no significant difference in the expression of JNK and c-JUN protein between the groups(P > 0.05).4 Changes of GRP78,alpha-syn and CDNF gene expression4.1 α-syn: After 14 days of administration,the expression of α-syn gene in the model group was significantly increased compared with the normal group(P<0.01).Compared with the model group,the expression of α-syn gene was significantly decreased in the drug-administered group(P< 0.01).4.2 GRP78 and CDNF: After 14 days of administration,the expression of GRP78 and CDNF genes in the model group was significantly decreased compared with the normal group(P<0.01).Compared with the model group,the expression of GRP78 and CDNF genes was significantly increased in the drug-administered group(P<0.01).Conclusions1 CRSJG can improve the behavioral disorder of PD model rats,increase the TH content in substantia nigra of PD model rats,and resist the apoptosis of dopamine neurons.2 CRSJG can increase the expression of CDNF,a new neurotrophic factor in substantia nigra of PD rats.3 CRSJG may play a neuroprotective role on PD by alleviating the damage of endoplasmic reticulum stress in substantia nigra neurons of PD model rats,increasing the expression of GRP78 and reducing the abnormal aggregation of alpha-syn,inhibiting the activity of JNK signaling pathway. |
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