| Objective:Buxinruanmai particles(BXRMP)made by Jiangsu Province Hospital of TCM,which consist of Rhodiola,Radix,dogwood,leeches,ginkgo biloba and Polygonum,can invigorate heart and kidney and remove blood stasis.Several experiments have demonstrated significant effects of BXRMP in protecting coronary heart disease and angina.In the present study,we explore further the protective effects and potential mechanisms of BXRMP on myocardial ischemia.Methods:The SD rats model of myocardial ischemia was developed by injecting vasopressin(Pit)(1.5u/kg)into sublingual intravenous.The effects of BXRMP on ECG T-wave height was observed on 5s、15s、30s、45s、1、3、5、10 min after injection.The dog model of myocardial ischemia was developed by ligating the left coronary anterior descending artery.The EECG was recorded before the ligation and after 15min ligation,also injection of pit 30、45、60、90、120、150、180 min by epicardial electrocardiogram system.Through the EECG,Σ-ST and N-ST was counted.Changes of SAP、DAP、MAP and HR were collected and analyzed by Power-lab software.Electromagnetic flowmeter was used to measure the coronary blood flow.The heart was taken to be stained with TTC.After that,the effects of BXRMP on infarct size were observed.The SD rats model of acute myocardial ischemia was developed by injecting isoproterenol hydrochloride(ISO)(30mg/kg)into subcutaneous and roots of the limbs.The effects of BXRMP on the displacements of ST region was observed on 1、2、3、5、10、15、20、30 min after injection.Orbital blood was collected after 30 min after modeling.Then,serum was separated and LDH,CK activity,Na+-K+-ATPase,inflammatory cytokines(IL-1β、IL-6、TNF-α),PPARa mRNA and protein expression,cardiac pathology were determined.Results:1、In terms of the acute myocardial ischemia of SD rats induced by Pit,the T-wave changes were significantly inhibited in each dose group.The heights of T-wave were significantly decreased from 5s to 5 min in different dose groups compared with the model(P<0.05;P<0.01).2、In terms of the dog model of the myocardial ischemia,Σ-ST and N-ST moved up markedly,comparing each dose group with the model(P<0.05;P<0.01).But changes of SAP、DAP、MAP and HR were not significant.The coronary blood flow in each dose were improved in different degrees(P<0.05),indicating the dose-effect relationship.The effects of three doses of BXRMP on infarct size were significantly different with the model(P<0.05;P<0.01).3、The effects of BXRMP on ST region in myocardial ischemia induced by ISO indicated that LDH and CK were improved significantly and dose-effect dependent.Compared with the Xinyuan Capsule,BXRMP could protect the heart through strengthening the body’s tolerance to ischemia,stabilizing the membrane and reducing the areas of myocardial necrosis.4、BXRMP could improve the activity of Na+-K+-ATP enzyme,indicating the important roles in sustaining energy metabolism of damaged myocardial cells and ion balance of intracellular and extracellular.5、BXRMP could significantly reduce serum IL-1β levels,which is dose-effect dependent and superior to Xinyuan Capsule.The absence of notable effects on IL-6、TNF-α showed that BXRMP protected endothelial function by regulating the secretion of IL-1β to inhibit the inflammatory response.6、BXRMP could improve the PPARa mRNA and protein expression levels,and maintain the integrity of myocardial cell membrane and mitochondrial structure.Conclusion:BXRMP can significantly protect SD rats from myocardial ischemia induced by Pit/ISO and protect dogs from myocardial ischemia induced by coronary artery ligation.The potential mechanism may be related to these factors as follows:improving the PPARa mRNA and protein expression levels,inhibiting the generation of IL-1β,suppressing inflammation response and sustaining energy metabolism of myocardial cells.In conclusion,BXRMP can protect ischemia myocardial cells through a variety of ways. |
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