黄芪注射液抗心肌细胞再灌注损伤的作用及机制

Protective effect and possible mechanism of Astragalus injection in ischemia reperfusion cardiocytes

该研究采用离体兔心缺血再灌注模型和培养心肌细胞缺氧复氧模型，从器官和细胞两个水平，运用免疫组织细胞化学、流式细胞仪、免疫印记、RT-PCR，生化学检测等多种方法，较系统地研究了黄芪注射液抗再灌注损伤的作用和机制。特别是该论文从细胞信号转导角度研究了黄芪药物作用的分子药理机制．发现该药物具有调节抗再灌注损伤的MAPK细胞信号通路的作用．而这种作用很可能是其心肌保护效应的机制之一。并且特异性抑制剂并不能减弱黄芪作用，说明黄芪可能是通过多种途径发挥作用。

Objective Astragalus ＂survival＂ signaling attenuates apoptosis. We therefore examined the effects of Astragalus on reperfusion injury myocardial cells and assessed the role of p42/p44 MAPK signaling in Astragalus-induced protection. Methods Using a blood-perfused, parabiotic, Langendorff rabbit model, hearts underwent 45 minutes of normothermic ischemia protected with Astragalus or not, and 60 minutes of reperfusion. Hemodynamic parameter and myocardial enzyme leak were compared. Further studies were conducted on cultured myocytes. Rat ventricular myocytes were subjected to hypoxia 4 h and reoxygenation 2 h. Astragalus was applied to cells before or during ischaemia/reoxygenation and the extent of cell death and myocardial enzyme were determined. Results When intact hearts received astragalus during ischamia, Hemodynamic parameter and CK release and ischemic size were better, compared with control group （P〈0.01）.In cells, incubation with Astragalus before or during reoxygenation attenuated the extent of cell damage and also reduced the numbers of apoptotic cells. Reduction of anontosis was decreased by PD98059, an inhibitor of p42/p44 MAPK activation. Astragalus activated p42/p44 MAPK transiently in normoxic myocytes. Conclusions This study show that Astragalus attenuates cardiac myocytes injury during reperfusion and the mechanism perhaps involves p42/44 MAPK activition.