ET-1和NO对脂多糖引起的大鼠心肌收缩抑制作用的影响  

ENDOTHELIN-1 AND NITRIC OXIDE MEDIATED THE LIPOPOLYSACCHARIDE-INDUCED CARDIAC NEGATIVE INOTROPIC ROLE

作　　者：姚慧[1] 屠洁[2] 单绮娴[2] 夏强[2] 

机构地区：[1]杭州师范大学基础医学部,浙江杭州310036 [2]浙江大学医学院生理系,浙江杭州310058

出　　处：《中国应用生理学杂志》2009年第2期228-232,共5页Chinese Journal of Applied Physiology

基　　金：杭州师范大学科研基金资助(2008XMM04)

摘　　要：目的:观察内皮素-1(ET-1)和一氧化氮(NO)在脂多糖(LPS)引起的大鼠心肌收缩抑制中的作用及其可能机制。方法:大鼠腹腔注射LPS(10 mg.kg-1)建立败血症休克模型,应用Langendorff离体灌流心脏及单个心室肌细胞观察LPS对大鼠心肌动力学、心肌细胞内钙稳态的影响及ET-1和NO在其中的作用。结果:①LPS处理4 h可使大鼠血清中NO代谢产物NO2-/NO3-水平和ET-1含量显著增加;②在离体Langendorff灌流心脏上,LPS组心脏收缩功能受到抑制,心率与发展压的乘积(RPP)显著降低,左心室舒张末压(LVEDP)升高。预先用iNOS特异性抑制剂aminoguanidine(AMG)(100 mg.kg-1i p)或ETA受体阻断剂BQ-123(1mg.kg-1i p)处理15 min,均可部分逆转LPS引起的心脏收缩功能抑制;两者联合预处理15 min则基本消除LPS引起的心脏收缩功能抑制;③LPS处理4 h后,咖啡因诱导的单个心室肌细胞内钙瞬变幅度较对照组显著降低(P<0.01),同时LPS显著抑制心室肌细胞肌浆网Ca2+-AT-Pase活性(P<0.01);BQ-123或AMG预处理15 min可部分逆转LPS对心室肌细胞内钙瞬变的抑制效应,但均不能逆转LPS对肌浆网Ca2+-ATPase活性的抑制作用。结论:ET-1和NO均参与LPS引起的大鼠心肌收缩抑制作用及细胞内钙储备降低,但两者对LPS所致肌浆网Ca2+-ATPase活性降低无影响。To investigate the effects of endothelin- 1 （ ET- 1 ） and nitric oxide （NO） on lipopolysaccharide （ LPS ）-induced myocardial dysfunction, and explore the related underlying mechanisms. Methods： Experimental septic model was established by intraperitoneal injection of LPS （10 mg·kg^-1）. The study was carried out on the isolated rat hearts to determine the roles of ET-1 and NO in the effect of LPS on the cardiac contractility and on the isolated rat ventficular myocytes model to observe the [ Ca^2＋ ]i homeostasis in cardiac myocytes. Results： ①The levels of serum NO2^-/NO3^- and plasma ET-1 were markedly increased by LPS treatment for 4 hours. ②LPS induced the decrease in rate-pressure preduct（RPP）, and increase in left ventricular end-diastolic pressure（LVEDP） in the isolated perfttsed rat hearts. Pretreatment with either aminoguanidine（AMG） （ 100 mg·kg^-1, i p） or BQ-123（ 1 mg·kg^-1, i p） partially attenuated LPS-induced myocardial depression. When these two drugs were simultaneously given, myocardial depression elicited by LPS was almost abolished. ③LPS significantly decreased the amplitude of caffeine induced [ Ca^2 ＋ ] i transients compared to the control cells. The activity of SR Ca^2 ＋ -ATPase was significantly decreased in the cardiac myocytes from LPS-treated rats. Single pretreatment with either AMG or BQ-123 did not attenuate the impairment of SR Ca^2 ＋ -ATPase induced by LPS. Conclusion： ET- 1 and NO mediate myocardial dysfunction in hearts isolated and decrease [ Ca^2 ＋ ] i transients in cardiac myocytes from LPS-treated rats. But neither ET-1 nor NO participates in the impairment of SR Ca^2＋ -ATPase induced by LPS.

关 键 词：内皮素-1 一氧化氮 脂多糖 心肌抑制 

分 类 号：R331.3[医药卫生—人体生理学]