Study On The Relationship Between Qi Deficiency And Blood Stasis Syndrome After Percutaneous Coronary Intervention And Polymorphisms Of Cyp2c19*2 Gene And Intervention Effect Of Nao Xin Tong Capsule

Part I Analysis of the clinical risk factors of Traditional Chinese Medicine (TCM) and Western Medicine affecting prognosis of percutaneous coronary intervention (PCI)ObjectiveTo research the clinical risk factors of TCM and Western Medicine affecting the prognosis in patients undergoing PCL and observe the effect of qi deficiency and blood stasis syndrome after PCI on antithrombotic treatment, and analyze the relationship between qi deficiency and blood stasis syndrome after PCI and polymorphisms of CYP2C19*2 gene.Medthods1.505 CHD patients after receiving successful PCI were adopted in this study.They were divided into with major adverse cardiac events (MACE) group and without MACE group.Multivariate logistic analysis was used to analyze the independent influencing factors of prognosis after PCI.2.We adopted 256 CHD patients after receiving successful PCI.After 1 week of standard antithrombotic treatment, TCM syndromes were differentiated into qi-deficiency blood-stasis type and non-qi-deficiency blood-stasis type.All patients detected platelet count (PLT) n maximum platelet aggregation rate (MPA)% plasma von Willebrand factor (vWF) n platelet membrane glycoproteinsⅡb/Ⅲa (GPⅡb/Ⅲa)%prothrombin fragment 1+2 (Fl+2) and fibrinogen (FIB)3.505 CHD patients after receiving successful PCI were adopted in this study. TCM syndromes were differentiated into qi-deficiency blood-stasis type and non-qi-deficiency blood-stasis type after 1 week of standard antithrombotic therament. All patients were genotyped for the polymorphisms of CYP2C19*2 by PCR-RFLP, and the genetic variants frequencies were compared in subjects.Results1.The univariate analysis and logistic regression analysis indicated that qi deficiency and blood stasis syndrome^ more than 70% in maximum platelet aggregation rate (MPA)> the level of plasma von Willebrand factor (vWF) and CYP2C19*2 gene mutation were the independent risk factors of MACE in the following 1 year after PCI (P<0.01) 2.Compared with the non-qi- deficiency blood-stasis group after PCI, the MPA,vWF and GPⅡb/Ⅲa were obviously higher in qi- deficiency blood-stasis group (P<0.01), and there were no statistical difference of PLT,F (1+2) and FIB between the two groups (P>0.05)3.The patient genotype distribution was in Hardy-Weinberg equilibrium. Partitions ofχ2 method showed that GA+AA was higher in qi-deficiency blood-stasis group than in non-qi-deficiency blood-stasis group (χ2=26.952, P<0.01).After adjusting for common risk factors of CHD after PCI, logistic regression analysis indicated that the odds ratios (OR) of GA+AA (vs GG) genotype for qi deficiency and blood stasis syndrome was 2.551 (95%Cl:1.463-4.446, P=0.001) with the reference category of non-qi-deficiency blood-stasis syndrome.Conclusions1.Qi deficiency and blood stasis syndrome,70% cut-off in MPA,the level of plasma vWF and CYP2C19*2 gene mutation are very important to evaluate the prognosis for CHD patients after receiving successful PCI.2.Qi deficiency and blood stasis syndrome after PCI affects platelete activation and ndothelial function on standard antithrombotic treatment, whereas the number of blood platelet and coagulation function may be not. Qi deficiency and blood stasis syndrome is the independent risk factor of MACE in the following 1 year after PCI.3.The GG+AA genotype may be some heritable susceptibility to disease of qi deficiency and blood stasis syndrome after PCI. PartⅡThe directive effect of conjoint analysis qi deficiency and blood stasis syndrome and CYP2C19*2 gene mutation on individualized antithrombotic durg selection after percutaneous coronary intervention (a prospective, randomized, single-blind, controlled clinical trial)ObjectiveTo investigate the therapeutic effect of nao xin tong capsule on individualized antithrombotic treatment of patients undergoing PCI.Medthods54 CHD patients with qi deficiency and blood stasis syndrome and CYP2C19*2 gene mutation, who had received revascularization by PCI successfully, were randomized into the treatment group and the control group, both treated with conventional western medical treatment, but the treatment group combined, respectively, with nao xin tong capsule for 1 month.The investigating items included Chinese medicine syndrome scores, short and long-term efficacy and safety assessment of antithrombotic treatment. Resultsl.The baseline between the two groups was similar. Before treatment* there was no significant difference in Chinese medicine syndrome scores (P>0.05). After treatment, qi deficiency syndrome and blood stasis syndrome scores reduced significantly in the treatment group (PO.01) and the control group showed a higher qi deficiency syndrome score and lower depressive amplitude of blood stasis syndrome score (PO.01),while significantly superior to qi deficiency syndrome and blood stasis syndrome scores in the treatment group (P<0.05).2.Before treatment, there were no statistical difference of PLT,MPA. vWF,GPⅡb/Ⅲa, F(1+2) and FIB (P>0.05). After treatment, the indicators of MPA,vWF,GPⅡb/Ⅲa,F (1+2) and FIB went down in both groups (P<0.01), but the lowering in the control group were lesser (P0.05).The change ofPLT was insignificant between two groups (P>0.05)3.During the period of one-month follow-up,3 MACE and zero MACE occurred in the control group and the treatment group respectively, no statistical difference was found between them (P>0.05)4.There was no major and minor hemorrhagic complication in the treatment group and the control group.Conclusions1.Nao xin tong capsule may decrease qi deficiency syndrome and blood stasis syndrome scores of ten days after PCI in patients with qi deficiency and blood stasis syndrome and CYP2C19*2 gene mutation.2. Combination of conventional western antithrombotic treatment and nao xin tong capsule shows better efficacy in inhibiting activity of blood platelet%alleviating endothelial cell damage and improving coagulation function.3.Along with nao xin tong capsule administration, there is a depress tendency for the occurrence of cardiovascular events during one month after PCI in patients with qi deficiency and blood stasis syndrome and CYP2C19*2 gene mutation.4.Combination of conventional western antithrombotic treatment and nao xin tong capsule may not increase the incidence of thrombocytopenia and bleeding complications. PartⅢEffect of nao xin tong capsule on the activity of cytochrome P2C19 (CYP2C19) in human microsomeObjectiveTo observe the effect of nao xin tong capsule on CYP2C19 activity in human liver microsome in vitro.MedthodMephenytoin (the probe drug of CYP2C19) was incubated with or without nao xin tong capsule in human liver microsome respectively.The concentrations of mephenytoin and its metabolity (4-OH mephenytoin) were determined by HPLC, and the CYP2C19 activity was reflected by the metabolite production (4-OH mephenytoin)ResultCompared with pre-incubation without nao xin tong capsule, the metabolite concentration of 4-OH mephenytoin had statistical difference in pre-incubation with nao xin tong capsule (150-250μg/ml)ConclusionNao xin tong capsule results in an induction of CYP2C19 activity of in vitro in a dose-depentent manner. The combination of nao xin tong with clopidogrel may be reinforce the effect of antiplatelet through the above-mentioned mechanism in patients with qi deficiency and blood stasis syndrome and CYP2C19*2 gene mutation after PCI.