Effects Of Chinese Herbs On Acute Myocardial Infarction And It's Synergic Acting Mechanism With Ischemic Postconditioning

The study consists of two parts:clinical study and experimental one.StudyⅠ:Clinical studyObjective:To evaluate the effect of Chinese herbs(CH) treament that is taken as a general intervention factor on the quality of life,clinical symptoms and prognosis in patients with AMI.Methods:A total of 98 AMI patients were designed into two cohorts.The 1st cohort which consisted of 53 AMI patients were subjected to the combined treatment of conventional CH and Western medicine(WM),which includes any of the 3 typesChinese patent medicine,herbal decoction and herbal injection,and is taken as a whole interfering factor,the other cohort patients which consisted of 45 AMI patients were treated with conventional WM only.A one-year follow-up was finished by the out-patient meeting or telephone inquiry,and medication cost,quality of life,clinical symptoms, heart function,the occurrence of end-point cardiovascular events were investigated and evaluated.Results:It showed that in the CH group,score of TCM symptoms and medication cost are significantly lower than that of the only WM group(P＜0.05).The total score of SF-36 and its sub-parts of RP(Role Physical),BP(Body Pain),MH(Mental Health) and GH(General Health) in the CH group are significantly higher than that in the only WM group(P＜0.05).There is no remarkable difference between the two groups concerning the occurrence of cardiovascular events(main cardiovascular events such as death and secondary ones such as post infarction angina pectoris) and heart function improvement(P＞0.05).Conclusion:CH treatment could improve clinical symptoms,quality of life,and reduce medical cost in AMI patients.Because of the limits of sample number and follow-up period in this study,the effect of CH treatment on reducing end-point cardiovascular events and improving heart function in AMI patients needs to be further explored.StudyⅡ:Experimental studyObjective:To observe whether there exists the synergistic effect of CH intervention and ischemic postconditioning in reducing ischemia/reperfusion injury and explore it's potential mechanism. Methods:Wistar rats were randomly divided into 6 groups of 16 each:(1) Sham operation group(group A);(2) Ischemic/reperfusion group(group B);(3) Ischemic postconditioning group(group C).The animals in the 3 groups were given administration of saline 2ml daily intragastrically for 14d;(4) Western medicine group(group D): intragastric administration of fosinopril 2ml(0.9mg/Kg) daily for 14d;(5) Supplementing qi and nourishing yin and detoxicating group(group E):intragastric administration of xinyue capsule+huanglian alkaloid 2ml(0.16g/Kg+0.081g/Kg) daily for 14d;(6) Activating blood circulation and detoxicating group(group F):intragastric administration of fufangchuanxiong capsule+huanglian alkaloid(0.40g/Kg+0.081g/Kg) 2ml daily for 14d.Thoracotomy was performed 1h after the last intragastric administration in group A, and the line was placed inferior to the left anterior descending coronary artery without ligation.In group B,the rat's left anterior descending coronary artery was ligated for 30m and then given a 1h persistent reperfusion.In the remaining groups,left anterior descending coronary artery was ligated for 30m,then followed by a 1m repeated ligation-reperfusion of 10s ligation,10s reperfusion,the procedure was performed for 3 times to simulate the process of in vivo ischemia postconditoning,and finally a 60m of complete reperfusion was made.Blood was draw from abdominal aorta and centrifuged to dissociated blood serum,and malondialdehyde(MDA),superoxide dismutase(SOD), high sensitive-C reactive protein(hs-CRP),Interleukin-1β(IL-1β),Interleukin-6(IL-6), MB isoenzyme of creatine kinase(CK-MB),cardiac troponinT(cTnT) were determined. Animals' heart was removed and myocardium tissue separated,myocardial infarction size was measured with N-BT staining method.Cut sheet was imbedded with paraffin. Myocardial pathological changes were observed with HE staining and the expression of TLR observed immunohistochemically.During the experimental procedure,the leadⅡECG at the time of 15,30min of ischemic,30,60min of reperfusion was recorded for ST segment elevation evaluation.Results:(1) Pathomorphology:Compared with group B,myocardial cell hypertrophy, inflammatory exsudation,cardiac muscle fibers disorders,karyopyknosis and hypochromatosis were all improved in PC group and all the drug-treated groups,and groupF showed the most obvious effects.Compared with group C,group DandF can diminish myocardium infarct size significantly(P＜0.01).(2) Immunohistochemical analysis:Compared with group B,TRL2 and TRL4 expression decreased significantly in group C,D,EandF(P＜0.01).Compared with group C,TRL2 and TRL4 expression decreased significantly in group EandF(P＜0.01);(3) Serum MDA and SOD changes: compared with group B,MDA decreased significantly in group C,D,EandF(P＜0.05), whereas there is no significant difference among the four groups(P＞0.05).Compared with group B,SOD increased significantly in group C,D,EandF(P＜0.05,P＜0.01). Compared with group C,SOD increased significantly in group DandF(P＜0.01);(4) Serum hs-CRP,IL-1β,IL-6 changes:Compared with group B,IL-1β,IL-6,hs-CRP decreased significantly in group C,D,EandF(P＜0.05,P＜0.01).Compared with group C, IL-1βdecreased significantly in group F(P＜0.05),IL-6 decreased significantly in group EandF(P＜0.05),hs-CRP decreased significantly in group E(P＜0.05);(5) Serum CK-MB and cTnT changes:Compared with group B,cTnT decreased in group C,D, EandF,but there was no remarkable difference among the 4 groups(P＞0.05);(6) ST segment change on leadⅡECG:Compared with group BandC,ST segment elevation was significantly reduced at the time of 15min of ischemic in group DandF(P＜0.01). Compared with group BandC,elevated ST segment was significantly fallen at the time of 30min of ischemic in group F(P＜0.01).Compared with group B,elevated ST segment was significantly lower at the time of 30min,60minof reperfusion in group C,D,EandF (P＜0.01).Compared with group C,elevated ST segment was significantly lower at the time of 30min of reperfusion in group C,D,EandF(P＜0.01);elevated ST segment was significantly lower at the time of 60min of reperfusion in group EandF(P＜0.05).Conclusion:(1) Postconditioning could improve ischemia-reperfusion injury,regulate inflammatory reaction,diminish myocardium infarct size;(2) The therapy of activating blood circulation and detoxicating(fufangchuanxiong capsule+huanglian alkaloid) could significantly enhance the SOD activity,reduce ischemia-reperfusion injury of myocardium;(3) Both the therapy of activating blood and detoxicating (fufangchuanxiong capsule+huanglian alkaloid) and the therapy of supplementing qi and nourishing yin and detoxicating(xinyue capsule+ huanglian alkaloid) could reduce the expression of TLR2 and TLR4,degrade the level of IL-1β,IL-6,hs-CRP,decrease the inflammatory response;(4) The therapy of activating blood circulation and detoxicating (fufangchuanxiong capsule+huanglian alkaloid) could decreased ECG ST segment elevation,promote myocardial tissue perfusion,and reduce myocardial infarct size significantly.