| Research Purposes:1.Through applying the randomized,double-blind,placebo-controlled comparison method,to research the possible mechanism on repairing arterial endothelial injury of the Tongguan capsule with percutaneous coronary intervention(PCI) of coronary heart disease(CHD).2.Based on the rat carotid artery balloon injury models,to obsere the correlation of the Tongguan capsule,VEGF and SDF-1 during endothelial repairing and intimal hyperplasia after carotid artery injury,to investigate the possible mechanism on repairing arterial endothelial injury of the Tongguan capsule.Methodology:1.Clinical research:Taking the randomized,double-blind,placebo-controlled comparison method,sixty patients treated with percutaneous coronary intervention(PCI) were randomized to two groups:group A(n=30,treated with Tongguan Capsule and conventional western medicine) and group B(n=30,treated with placebo and conventional western medicine).Observation:(1) The clinical characteristics were evaluated;(2) The level of the serum VEGF and SDF-1 with enzyme-linked immunosorbent assay(ELISA) 30 days before and after the operation;(3) The returning of ECG ST-segment at 2h time point after the operation;(4) Inspect TEE,LVEF(left ventricular ejection fraction) and ventricular wall motion parameters at 30 days before and after the operation,and observe the cardiac function classification of NYHA.(5)Major adverse cardiac events(MACE) including death,nonfatal myocardial infarction(MI),target vessel revascularization(TVR) and new heart failure were followed in 1 month after PCI.2.Experimental research:A total of 60 male Sprague-Dawley rats which the left common carotid arteries injured were randomly divided into3 groups(n=18):Group 1(10mg/kg/d of PS was given after injury),group 2(2mg/kg/d of Simvastatin was given after injury)and group 3(600mg/kg/d of Tongguan capsule was given after injury). 18 rats from each group were euthanized by exsanguination at week 4,week 8 and week 12 after injury.The injuried left common carotid arteries were carefully removed for HE and elastic fibers staining,intima area,media area and IA / MA were performed in IPP6.0.which is a automatic computerized imaging analysis system.To observe the reparation after injury of blood vessel endothelium through detection of VEGF and eNOS with immunohistochemistry.Research Results:1.Clinical research:(1)There had no difference between the treatment group and the control group before the operation.The level of VEGF and SDF-1 all decreased significantly at 30 days in the the treatment group and the control group,at the same time, The level of VEGF and SDF-1 at 30 days after the operation in the treatment group and which had significant differences compared with the control group(P＜0.01,P＜0.01)。(2) ST-segment resolution all decreased significantly at 2 hours in the treatment group and the control group,but there had no differences between the treatment group and the control group at 2 hours after the operation(P＞0.05).(3)Ate the 1 month time point after the operation,the LVEF and ventricular wall motion parameters of the both groups are improved(average P＜0.05), indicating that the PCI treatment can significantly improve the cardiac functions of the CHD patients.Meanwhile,compared with the control group, the LVEF ventricular wall motion scores of the Tongguan capsule treatment group are further improved.(4)Main Adverse Cardiac Events:At 30 days follow-up,there didn't exist statistics difference in the incidence of death,non-fatal MI and TVR between two groups.The incidence of new heart failure of the treatment group was statistically lower than the control group(P=0.045),thus,the incidence of MACE in the treatment group was statistically lower than the control group (P=0.024).2.Experimental research on animals:(1) Histological Observation:Artery endothelium after balloon denudation, internal elastic lamina become flat from wavy and lost its elasticity.4 weeks after the operation,morphological analysis demonstrated that there were markedly differences in the area of neointima proliferation among all the groups.In comparison with Group 1,intima area(IA) of tunica intima in rats after balloon injury in Group 2 and group 3 decreased obviously(average P＜0.01) at 4 weeks,8 weeks and 12 weeks.The trends of ratio of IA/MA in rats were similar to which of IA.(2) VEGF detected by immunohistochemical assay:the expression of VEGF of Group 3 increased obviously at week 12(P＜0.05).(3) eNOS detected by immunohistochemical assay:In comparison with Group 1, the expression of eNOS in tunica intima in rats after balloon injury in Group 3 increased obviously(P＜0.01),The changes of the expression of eNOS of Croup 2 were similar to Group 3.There had no difference between Group 2 and Group 3.(4) detection of VEGF and SDF-1 with enzyme-linked immunosorbent assay(ELISA):In comparison with Group 1,the expression of VEGF and SDF-1 in blood serum in rats after balloon injury in Group 3 increased obviously(P＜0.01),The changes of the expression of VEGF and SDF-1 of Group 2 were similar to Group 3.In comparison with Group 2,the expression of SDF-1 of Group 3 increased obviously at week 8(P＜0.05),however the expression of VEGF of Group 3 increased obviously at week 12(P＜0.05).Conclusion:1.Rat carotid balloon-injured model can simulates the process of pathological changes of endothelial injury and restenosis after percutaneous coronary intervention(PCI).2.After rat carotid artery balloon injury,VEGF and SDF-1 could restrain proliferation and restenosis.3.The level of VEGF and SDF-1 decreased after the PCI operation is related to coronary artery reoanalization.At the same time the level of VEGF and SDF-1 increased in the Tongguan treatment group,Tongguan capsule played an important role in the improvement of left ventricular systolic function by promoting angiogenesis and reendothelialization after PCI through mobilization of EPCs.4.Tongguan capsule inhibited intimal proliferation and restenosis by upregulating the VEGF,eNOS and SDF-1 expression.
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