中性粒细胞对缺血心肌的损伤作用及药物防治的研究

Study of the injurious effects of neutrophils on myocardium and their medicinal therapy in rabbits

异丙肾上腺素皮下注射2h循环白细胞即明显升高,反复注射3 d心肌方发生严重坏死。预先用环磷酰胺耗竭循环白细胞再致伤动物则心肌坏死明显减少。另一方面,对照组兔中性粒细胞(Neu)吞噬功能显著增强,酸性磷酸酶释放明显增多,显示Neu功能亢进;试用地塞米松、吲哚美辛抑制Neu功能再致伤动物,则心肌中前列腺素E_2及丙二醛含量明显降低,超氧化物歧化酶活性显著升高,心肌坏死也随之明显减少,并与功能呈显著正相关。上述结果表明,Neu通过释放溶酶体酶。产生氧自由基及花生四烯酸代谢产物等方式可能在心肌梗塞发病中有重要病理学作用,用药物调控Neu功能对心肌梗塞可产生一定防治效果,这为寻找防治心肌梗塞的新药开辟了新途径。

It was found that there was a significant increase of the number of circulating leucocytes 2h after a subcutaneous injcetion of isoprenaline and severe myocardial necrosis occurred after consecutive injections for 3 d.Cytoxan-induced depletion of leucocytes resulted in an obvious decrease of the percentage of myocardial necrosis.In the control.the neutrophilic phagocytosis was enhanced and their release of acid phosphatase elevated greatly,which indicates that the neutrophils are in an activated state.After the.neutrophils were inhibited with dexamethasone or indomethacint significant reduction of the contents of prostaglandin E2 and malondialdehyde and an increase of superoxide dismutase activty in the myocardium were observed and consequently myocardial necrosis was greatly alleviated.Our findings suggest that neutrophils might play an important role in the pathogenesis of myocardial infarction through the release of lysosomal enzymes and the production of oxygen-derived free radicals and certain metabolites of arachidonic acid,and proper regulation of the neutrophilic functions could exert prophylactic effects on myocardial infarction.This might be a promising direction to look for more effective drugs to treat myocardial infarction.