| Objective:Treatment of cardiovascular disease is the focus of today's social studies. Ischemia-reperfusion injury is the key link which is the development of many cardiovascular diseases.How to alleviate the cardiovascular damage caused is now a hot research. The shortcomings of ischemic preconditioning limit its clinical application.It is proposed the concept of pharmacological preconditioning, through drugs stimulating or simulating the emergence of endogenous protective substances on myocardial protection. In previous work, we have shown that AsⅣcould protect the damaged myocardium in a preliminary study. It was found that AsⅣcan enhance the activity of SOD, reduce the role of peroxidation,and improve electrocardiogram,reduce infarct size, induce the NO generation. NO is an important trigger factor pretreatment. On this basis we assume that Astragalus injection can stimulate or simulate the body's own endogenous anti-injury substance,mimic ischemic preconditioning. It can replace preconditioning and produce preconditioning-like protective effect. This is great vale for the development of new drugs or new use of old drugs .Astragalus injection is a perennial herb and more expensive Chinese herbal medicine with roots, mainly distributes in north China. Astragalus injection contains flavonoids, polysaccharide,saponin,alkaloids, amino and microelements other active ingredients. Astragalus injection has been applied cardiovascular and achieved significant effective ,because it has its clear radicals, antagonistic calcium overload, protection endothelial cell, improve cardiac function multiple roles. Astragalus injection has significantly enhanced myocardial contractility, dilated coronary , protected myocardial cells , improved heart functions, expansed of blood vessels, lowered blood pressure;Astragalus injection can inhibit platelet aggregation, lower blood viscosity and improve microcirculation; Astragalus injection can increase adrenaline cortex function,and improve kidney function; Astragalus injection also prevents glycogen reduce and protects liver. Currently Astragalus injection is widely used clinical treatment. Cardiovascular protective effect of Astragalus injection molecular mechanism is still a lack of system. This study explores the protects and mechanisms of the Astragalus injection on myocardial ischemia-reperfusion injury in rats. Methods:1.Animal experiments: Rats were randomly divided into 4 groups, i.e,control group,ischemia/reperfusion group,Astragalus injection pretreatment Preconditioning,Ischemia preconditioning group. The left anterior coronary artery was ligated to establish the animal model of myocardial ischemia reperfusion injury. The content of LDH ,MDA and the activity of SOD in the myocardium were detected,the ECG is compared, the effect of against Astragalus injection cardiomyocyte apoptosis was observed.2.Cell level experiment: Cultured neonatal rat cardiomyocytes were divided into:①Control group ;②H2O2 group, in which cells were treated with H2O2 (0.15mmol? L-1) for 5 h ;③AI+H2O2 group,in which cells were pretreated with AI (with final concentration of 90 g?L-1) 30min before H2O2 treatment.④AI+ H2O2 + L-NAME (20μg? L-1 ). The cardiomyocyte viability was analysed by MTT assay, lactate dehydrogenase (LDH) activity and nitric oxide (NO) content were detected in culture media. ROS were measured by laser-confocal- microscopy system,mitochondrial memberane potential(Δψm) and apoptosis rate were measured by flowcytometry.Results:1.The results showed that Astragalus injection decreased the LDH and MDA contents ,improved SOD activitie. Astragalus injection also decreased the number of apoptosis cells in myocardium injuried by ischemia / reperfusion in rats.2.Cardiomyocyte viability in AI (90g?L-1) groups was higher than that in H2O2 group ( P<0.01). Compared with H2O2 group,LDH activity and reactive oxygen species (ROS) content in AI (90g?L-1)group were decreased (P<0.01),NO content were increased (P<0.01),Δψm of cardiomyocytes were increased and apoptosis rate were decreased. Compared with AI (90 g?L-1)group after treatment combining with L-NAME ,LDH activity and ROS content in AI (90 g?L-1)group were increased (P<0.01),NO content were decreased (P<0.01),Δψm of cardiomyocytes were decreased and apoptosis rate were increased (P<0.05).CONCLUSION:1.AI reduces ischemia-reperfusion injury in rats caused by the incidence of arrhythmias, improves ischemic myocardial injury caused by pathological changes,inhibites cardiomyocyte apoptosis,reduces injury.2.AI can protect mitochondria,reducing the membrane permeability, increasing membrane potential,inhibiting cardiomyocyte apoptosis.3.AI can protect cardiomyocytes from MIPI by improving cell antioxidant ability and increasing NO content ,inducing pharmacological preconditioning, reducing apoptosis. |
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