过量肾上腺素致小鼠肺水肿的机制研究

Mechanism of murine pulmonary edema caused by injection of an overdose of adrenaline

目的探讨过量肾上腺素致小鼠肺水肿的机制。方法经腹腔注射过量肾上腺素建立小鼠肺水肿模型,并分组给予不同浓度的普萘洛尔、美托洛尔、酚妥拉明、生理盐水,或单独注射去甲肾上腺素,比较各组间小鼠肺系数、肺组织病理学变化和呼吸活动等的改变;观察比较单独注射肾上腺素组与注射肾上腺素后分别加注阿托品、普萘洛尔、美托洛尔组小鼠心电图的变化;观察比较注射肾上腺素和注射生理盐水对照鼠心肌超微结构形态。结果肾上腺素组小鼠肺系数大于生理盐水组(P<0.05);加注酚妥拉明组小鼠肺系数明显小于肾上腺素组(P<0.05);加注普奈洛尔与加注美托洛尔各组小鼠肺系数均高于生理盐水组(均P<0.05),而与肾上腺素组无明显差别(P>0.05);去甲肾上腺素组小鼠肺系数显著高于生理盐水组(P<0.05);注射肾上腺素的各组小鼠均见到不同程度肺组织充血和渗出,但联合注射酚妥拉明组小鼠肺组织病变较轻;注射肾上腺素小鼠给药数分钟内心率显著降低并伴明显的节律异常,加注大剂量阿托品可拮抗此效应。结论过量肾上腺素致小鼠急性肺水肿主要由外周血管α受体强烈兴奋收缩引起;给药后小鼠心率减慢、节律异常可能由外周血管阻力增加的反射效应所致。

Objective To explore the mechanism of murine pulmonary edema caused by injection of an overdose of adrenaline.Methods Models of murine acute pulmonary edema were established by injection of an overdose of adrenaline（Ad）.The mice of different groups were then given intraperitoneal injection of certain concentration of propranolol（Pro）,metoprolol（Me）,phentolamine（Ph） or normal saline（NS） respectively and the mice of group noradrenaline（NA）were injected noradrenaline.The degrees of pulmonary edema were judged by comparing the average pulmonary coefficients,histopathological changes and resepiratory conditions between different groups.The electrocardiogram changes between the group Ad and the group atropine（Atro）,propranolol,metoprolol were compared and the changes of myocardial ultramicrostructure of the group Ad and the group NS were observed.Results The average pulmonary coefficient of group Ad was apparently higher than that of group NS（P0.05）.The average pulmonary coefficient in group phentolamine was significantly lower than that of group Ad（P0.05）.The average pulmonary coefficient of group propranolol,metoprolol was higher than that of group NS（P0.05）,but there were no significant difference between the average pulmonary coefficient in group Ad and that of group propranolol,metoprolol（P0.05）.The average pulmonary coefficient of group NA was apparently higher than that of group NS（P0.05）.Pulmonary congestion and exfiltration occured in different degree in group Ad,while this process was minor in group phentolamine.The heart rate decreased apparently and cardiac rhythm became abnormal in minutes after injection of Ad.Injection of a large dose of atropine immediately after Ad injection could produce an antagonistic effect.Conclusion Overdose administration of adrenaline could induce acute pulmonary edema by strongly exciting α-receptors in peripheral blood vessels in mice.Accordingly,the depressed heart rate and abnormal cardiac rhythm after injection of an overdose of Ad could be mainly related to the vasomotor center inhibitory action to the heart caused by increased peripheral vascular resistance（depressor reflex）.