| ObjectiveWe aim to explore the mediating effects of plasma metabolites and blood biochemical indexes in PD by analyzing the differences in plasma metabolites and blood biochemical indexes in PD patients.MethodsIn this study,plasma samples of 30 pairs of PD patients and their healthy spouses were collected for non-targeted metabolomics analysis and serum samples were tested for blood biochemical indexes.First,we determined differential metabolites between two groups using Wilcoxon rank-sum tests(p<0.05).Moreover,orthogonal partial least squares discriminant analysis(OPLS-DA)was used to identify differential metabolites that were significantly associated with PD(VIP>1)for further analysis.Second,clusters of co-abundant plasma polar metabolites and molecular lipids were identified using the the weighted gene co-expression network analysis(WGCNA).The metabolite clusters with the highest correlation were taken an intersection with the differential metabolites.Then,the difference of blood biochemical indexes between the two groups was analyzed and statistically significant difference indexes between the two groups were screened.Finally,the correlation between intersection plasma metabolites and differential blood biochemical indexes was analyzed.Further,the mediating effects of plasma metabolites and blood biochemical indexes with significant correlation were analyzed.ResultsAccording to the analysis of plasma metabolites and blood biochemical indexes of 30 pairs of PD patients and their healthy spouses,the main results are as follows:1、We identified 13 known different polar metabolites and 23 different lipid molecules based on the non-targeted metabolite profiles generated by the mass spectrometry platform(VIP>1、FDR<0.05).WGCNA analysis showed a significant positive correlation between MEgreen module and PD in negative ion mode(r=0.79,p<0.05),MElightcyan module was significantly positively correlated with PD in positive ion mode(r=0.66,p<0.05),including 94 polar metabolites(38 known and56 unknown).13 polar metabolites(3-methoxytyrosine,propyl galiate,phenthoate,tribenuron methyl,ferulic acid,isoferulic acid,trans-cinnamate,3,4-dihydroxyphenylglycol O-sulfate,N-acetylvanilalanine,3-(sulfooxy)benzenepropanoic acid,l-tyrosine methyl 4-sulfate)were increased in PD patients.2、In the comparison of 32 blood biochemical indexes among two groups,except for the difference in 8 blood biochemical indexes,there was no difference in other blood biochemical indexes.Specifically,the levels of homocysteine,estimated glomerular filtration rate and albumin in PD patients were higher than those in the control group,while the levels of uric acid,total cholesterol,triglyceride,potassium and creatinine in PD patients were lower than those in the control group.3 、 After the correlation analysis of 13 plasma metabolites and 8 blood biochemical indexes,4 of them were significantly correlated with 10 metabolites(r>0.5 or r<-0.5).The mediating effects of significantly correlated metabolites and blood biochemical indexes were analyzed that trans-cinnamate(mediated proportion=67%,pmediation < 0.001),ferulic acid(mediated proportion=69%,pmediation < 0.001),isoferulic acid(mediated proportion=81%,pmediation < 0.001)had mediating effect on the association between uric acid and PD.3,4-dihydroxyphenylglycol o-sulfate had mediating effect on the association between homocysteine and PD(mediated proportion=98%,pmediation < 0.001),and the association between total cholesterol and PD(mediated proportion=74%,pmediation < 0.001).ConclusionsMediation analysis showed that cinnamic acid derivatives may affect the level of oxidative stress and 3,4-dihydroxyphenylate o-sulfate may affect PD by affecting autonomic nervous function.These results indicate that blood biochemical indexes can affect PD through plasma metabolites as intermediate variables.Our study contributes to further mechanism research and provides a new direction to explore the mechanism by which metabolites affect PD. |
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