| Objective To explore the relationship between the compatibility of LiangxueTongyu Prescription compound and multi-dimensional efficacy,and optimize the compatibility ratio of the compound.To clarify the spectrum-effect relationship of the serum metabolite of the compound,and reveal the multi-channel and multi-effect comprehensive regulation mechanism of the compound.Thus the scientific connotation of the compatibility of the traditional Chinese medicine compound was clarified.Methods Part I:Correlation analysis and model construction of Chinese medicine and effect index of Liangxuetongyu prescription:Each Chinese medicine was regarded as a study factor,thus different Chinese medicines formed 12 dosage levels and 12 matching groups based on uniform design.After interventions,the effects,including the brain edema in the AICH rat model,behavioral assessment scores,and IL-6,TNF-α,IL-10,D-dimer,and AQP-4 in the serum,were used to establish a quantitative model of the drugs and the effects.Pearson correlation analysis was conducted to find the association between 8 traditional Chinese medicines and effect indicators,in order to screen for traditional Chinese medicines and its polynomial interaction terms that had a significant effect.Finally the traditional Chinese medicine-effect regression prediction models were built,and the most good compatibility ratio was found by synthesizing each effect index equation.Part Ⅱ:Spectrum-effect correlation analysis of the effect and the response components of Liangxuetongyu Prescription in the serum of the AICH rats:The AICH model rats were intervened with 12 matching groups of Liangxuetongyu Prescription by uniform design.The UPLC-QTOF-MS technology was used to detect and identify the metabolic components in the serum,and the Spearman correlation analysis of the chromatographic peak areas of the metabolites and the effects was performed.For metabolites with strong correlation,compound serum transition components were identified and marked as metabolic responders.Multiple linear regression model was performed on the chromatographic peak area of the metabolic response components and the effect index.Principal component analysis was performed on the metabolic response components to extract the principal components and calculate the principal component scores.Stepwise regression analysis was applied with the limited principal components representing the response metabolites and the effect indicators to establish the spectrum-effect correlation of Liangxuetongyu Prescription to intervene in AICH model.Results Part Ⅰ:A total of 7 Chinese medicines and interaction items that have a significant effect on brain water content,and a total of 16 Chinese medicines and interaction items with a significant difference in brain coefficient,and a total of 30 Chinese medicines and interaction item with a significant difference in behavior score.There were 6 traditional Chinese medicines or interaction items with significant differences in serum IL-6,and 2 traditional Chinese medicines or interaction items with significant differences in serum D-dimer(P<0.05).On this basis,a total of 5 dose-response models were obtained through regression analysis(P<0.05).Considering all the effect indexes comprehensively,when the weight of each observation index is the same,the optimal weight ratio of raw herbs of Liangxue Tongyu Prescription is:Paeonia suffruticosa Andr:Panax notoginseng(Burk.)F.H Chen ex C.Chow:Pheretima aspergillum(E.Perrier):Acorus tatarinowii Schott:Rheum officinale Bail:Paeonia lactiflora Pall=1:2:5:2:4:3.Part II:A total of 238 significant correlations were found between the serum response components and effect indicators obtained under the positive ionization mode(ESI+),of which 10 metabolites related to behavior score and serum IL-6 have a strong correlation(|Spearman correlation coefficient|≥0.7).A total of 271 ignificant correlations were found between the serum response components and effect indicators obtained under the negative ionization mode(ESI-),of which 19 related metabolites related to behavior score and serum IL-6 have a strong correlation(|Spearman correlation coefficient|≥ 0.7).Through multiple linear regression modeling,a total of 7 sets of regression equations were obtained for metabolic response components and the effects(P<0.05).The principal component F1 can explain 38.1%of the serum IL-6 effect;the principal component F1 and the principal component F3 can explain 18.7%of the serum TNF-α effect.The principal component F1 contributes 61.8%to 29 metabolic response components.The principal components F1 and F3 contributed a cumulative rate of 69.05%to the 29 metabolic response components.Conclusion There are respective correlations and synergistic interactions between different effect indexes in the acute phase of intracerebral hemorrhage and the Chinese medicines of Liangxue Tongyu Prescription.The polynomial regression model reveals the linear and nonlinear relationship between different drug combinations and different effect indicators.The optimal ratio of Liangxuetongyu Prescription is conducive to reducing brain edema in AICH rat model,improving neurological deficit,inhibiting inflammatory process,and correcting coagulation function.The spectrum-effect relationship of 29 serum response components of AICH rats model with Liangxue Tongyu Prescription ’s intervention reveals the comprehensive multi-component and multi-effect mechanism on neurological protection and inflammation index improvement for stasis-heat syndrome in acute intracerebral hemorrhage. |
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