摘要
目的:研究干扰素-α(IFN-α)对大鼠离体心脏及其乳头肌的影响和可能机制。方法:采用离体Langendorff灌流心脏和离体右心室乳头肌模型,观察IFN-α对左心室发展压、左心室内压最大上升和下降速率、左心室舒张末压、心率、冠脉流量和乳头肌平均最大收缩力的影响。结果:在离体Langendorff灌流心脏上,IFN-α(10 U/m l、100 U/m l、1 000 U/m l、10 000 U/m l)浓度依赖性的抑制左心室发展压、左心室内压最大上升和下降速率,抬高左心室舒张末压,高浓度IFN-α增加冠脉流量,但对心率无明显影响。在离体右心室乳头肌模型上,IFN-α浓度依赖性的抑制离体右心室乳头肌的发展张力。一氧化氮合酶抑制剂左旋硝基精氨酸甲酯(L-NAM E,1-0 4m o l/L)预处理后,可阻断IFN-α在离体灌流心脏和离体右心室乳头肌上的负性肌力作用。同时,IFN-α(1 000 U/m l)预处理10 m in可以引起右心室乳头肌对β-肾上腺素受体激动剂异丙肾上腺素(ISO,1-0 9m o l/L^1-0 6m o l/L)浓度曲线的反应性降低,合用L-NAM E(1-0 4m o l/L)预处理后,可削弱IFN-α的作用。结论:IFN-α对大鼠离体心肌具有负性肌力作用,并且能降低乳头肌对β-肾上腺素受体激动剂ISO的反应性,以上作用可能部分是由一氧化氮介导的。
Objective： To investigate the effects and underlying mechanisms of interferon-α （IFN-α） on the isolated Langendorff perfused rat hearts and the isolated papillary muscles. Methods： The left ventricular developed pressure （LVDP）, maximal rise/fall rate of left ventricular pressure （ ±dP/dtmax）, left ventricular end-diastolic pressure （LVEDP）, heart rate （HR） and coronary flow（CF） were recorded in isolated Langendorff perfused rat hearts. The average contractile force was measured in the isolated papillary muscles of rat right ventricle. Results： IFN-α（10～10 000 U/ml） induced a concentration-dependent decrease of LVDP and ＋dP/dtmax and increase of LVEDP and CF in the isolated perfused rat heart（P〈0.05）,and decrease of the average contractile force of the papillary muscle （P〈0. 05）. Pretreatment with L-NAME （10.4 mol/L）,an inhibitor of nitric oxide synthase,attenuated the effect of IFN-α in the isolated rat hearts and the isolated papillary muscles （P〈 0. 05）. Isoproterenol （ISO, 10^-9～10^-6 mol/L） increased the contractile force of the rat papillary muscles in a concentration-dependent manner. Perfusion for 10 min with IFN-α at 1 000 U/ml attenuated the enhancing effect of ISO. Pretreatment with L-NAME reduced the effects of IFN-α on the isolated papillary muscles. Conclusion： IFN-α may induce a negative inotropic effect in normal and β-adrenergic activated cardiac muscles and this effect at least partly be mediated by nitric oxide.
出处
《浙江大学学报（医学版）》
CAS
CSCD
2007年第1期28-34,共7页
Journal of Zhejiang University(Medical Sciences)
基金
浙江省教育厅科研基金资助(20050723)
