| Objective: To study the clinical efficacy of Shuimuhening Prescription in the treatment of Parkinson’s disease and the difference in the efficacy of different subtypes of patients,and to explore the mechanism of the treatment of Parkinson’s disease based on the ubiquitin proteasome pathway.Methods: Clinical study.A retrospective cohort study was used to divide patients into two groups according to exposure factors(whether they received Shuimuhening Prescription treatment or not).The treatment group was Shuimuhening Prescription combined with Madopar standard treatment,and the control group was Madopar standard treatment.Patients were divided into AR subtype,TD subtype,and mixed type according to the Unified Parkinson’s Disease Rating Scale(UPDRS).Patients’ baseline data,safety indicators,and curative effect indicators before and after treatment were collected,including the UPDRS scale,TCM syndrome score quantification scale,and overall efficacy assessment.Experimental study.C57BL/6mice were subcutaneously injected with rotenone in the neck and back to establish a mouse model of chronic Parkinson’s disease.Mice with successful Parkinson’s disease were randomly divided into model group,Madopar group,Shuimuhening Prescription15 g/kg,30 g/kg,60 g/kg groups.The treatment group was intragastrically administered once a day in the morning and evening,and the solvent control group and the model group were given equal amounts of normal saline.After 4 weeks of continuous administration,observe behavioral changes in mice;the expression ofα-syn and TH in the substantia nigra of the midbrain were detected by immunohistochemistry;the expression of α-syn,TH and UPS-related protein E1,Parkin,UCH-L1,ubiquitin protein and m RNA in the substantia nigra of the midbrain were detected by WB and RT-PCR methods.Result:Clinical studies.1.There were no significant differences between the treatment group and the control group in the gender composition,age distribution,disease course,concomitant diseases,cultural level,and disease severity(P>0.05),and the baseline characteristics were consistent.2.UPDRS score: The UPDRS scores of the two groups of patients after standardized treatment were lower than before treatment(P<0.05);after treatment,the UPDRS score of the treatment group was lower than that of the control group(P<0.05);after treatment,the UPDRS score of the AR subtype treatment group was lower than that of the control group(P<0.05),but there was no statistical difference in the UPDRS score between the two groups of patients with TD subtypes(P>0.05).3.Quantitative table of TCM syndrome scores:TCM syndrome scores of the two groups after treatment were lower than those before treatment(P<0.05);after treatment,the TCM syndrome score of the treatment group was lower than that of the control group(P<0.05);TCM syndrome scores of the AR subtype and TD subtype treatment groups were lower than those in the control group(P<0.05).4.The overall efficacy of the two groups were evaluated,and the treatment group was better than the control group(P <0.05);the overall efficacy of the AR subtype and TD subtype treatment groups were better than those of the control group(P < 0.05).5.Good safety during medication.Experimental studies.1.Model evaluation: The subcutaneous injection of rotenone in the neck and back of C57BL/6mice reduced the number of TH-positive cells in the substantia nigra of the midbrain(P<0.01)and increased the expression of α-syn(P<0.01).The motor symptoms of Parkinson’s disease appeared in the model mice.2.Ethology: After the intervention treatment,the ethology of mice in Shuimuhening Prescription 15 g/kg,30 g/kg,and60 g/kg groups was improved compared with the model group(P < 0.01).3.Pathology: The results of immunohistochemistry showed that the expression of α-syn protein and m RNA in the substantia nigra region of each TCM treatment group was reduced compared with the model group(P<0.01),and the number of TH-positive cells and m RNA was higher than that of the model group(P<0.01).4.UPS pathway:After treatment with Shuimuhening Prescription,WB and PCR results showed that the expression of TH,UPS-related proteins E1,Parkin,UCH-L1,and ubiquitin protein and m RNA in the substantia nigra region of each TCM treatment group were higher than those of the model group(P<0.01),the expression of α-syn protein and m RNA was lower than that of the model group(P<0.01).Conclusion: 1.Shuimuhening Prescription combined with Madopar have a definite curative effect on Parkinson’s disease,which can reduce the Unified Parkinson’s Disease Rating Scale(UPDRS)score,improve the TCM syndromes of patients,and have good safety.2.Shuimuhening Prescription can promote the degradation of α-syn by regulating the UPS function,reduce the damage of abnormally aggregated α-syn to dopaminergic neurons,and improve the motor function of mice with Parkinson’s disease. |
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