白花前胡及前胡甲素对心肌缺血再灌注大鼠IL-6水平及Fas、bax、bcl-2蛋白表达的影响

Effects of Peucedanum Praeruptorum Dunn and dl-Praeruptorin A on IL-6 Level and Fas, bax, bcI-2 Protein Expressions in Ischemia-Reperfusion Myocardium of Rats

目的:研究中药白花前胡及其有效成分对缺血再灌注心肌IL-6水平及凋亡相关蛋白表达的影响。方法:开胸麻醉大鼠左冠状动脉前降枝经30 min缺血及120 min再灌注;放射免疫法测定血清IL-6水平;免疫组化法和计算机图像分析系统检测心肌Fas,bax及bcl-2蛋白表达;苏木精-依红染色法于光镜下观察嗜中性白细胞浸润。结果:白花前胡粗提物及前胡甲素(Pd-Ia)在降压和不影响心率的情况下,减少IL-6水平及Fas,bax,bcl-2蛋白的表达,增加bcl-2/bax的比率。IL-6水平与Fas,bax,bcl-2蛋白表达之间呈密切的线性正相关,而嗜中性白细胞只有轻微浸润。结论:白花前胡及Pd-Ia在防治缺血后心肌细胞死亡上显现新靶位,原因可能与心肌缺血再灌注期间机体自身调控即早基因IL-6,Fas,bax,bcl-2的表达有关。

Objective:Our aim was to investigate the effects of crude extract of Peucedanum praeruptorum Dunn (BQ) ,a traditional Chinese herb,and its active ingredient dl-Praeruptorin A (Pd-Ia) , on IL-6 level and apoptosis-related protein expressions in ischemic-reperfused myocardium. Methods: Left anterior descending coronary artery was subjected to 30-minute ischemia followed by 120-minute reperfusion in open-chest anesthetized rats. Serum IL-6 level was measured by using radioimmunization assay. Fas, bax, and bcl-2 protein expressions were detected with immunohistochemistry and computer image analysis system. The infiltration of neutrophils was observed by using Hematoxylin-Eosin staining with optical microscope. Results: Both BQ and Pd-Ia reduced IL-6 level and Fas, bax, bcl-2 expressions under conditions of hypotension and without bradycardia, but increased the ratio of bcl-2/bax. A close linearity and positive correlation existed between IL-6 level and Fas, bax, bcl-2 expressions, whereas the infiltration of neutrophils was mild. Conclusion: The BQ and Pd-Ia produce a novel target for the therapeutic prevention of postischemic cell death in the heart. The reasons might be associated with automodulation of immediate-early gene expression including IL-6, Fas, bax, and bcl-2 during myocardial ischemia-reperfusion.