TNF-α的心肌负性肌力作用机制研究  

Mechanism of negative inotropic effect of tumor necrosis factor-α on rat myocardium

作　　者：傅琛[1] 曹春梅[1] 张晶[1] 夏强[1] 

机构地区：[1]浙江大学医学院生理学教研室,浙江杭州310031

出　　处：《浙江大学学报（医学版）》2003年第3期181-186,共6页Journal of Zhejiang University(Medical Sciences)

基　　金：浙江省自然科学基金青年人才专项资金资助(RC990 38)

摘　　要：目的 :探讨肿瘤坏死因子α(TNF-α)对心肌的负性肌力作用机制。方法 :采用离体大鼠乳头肌张力测定 ,细胞内双波长钙荧光检测和 ATP酶分析方法。结果 :1TNF-α抑制大鼠右心室乳头肌的收缩力 ,2 0 U/ ml和 2 0 0U/ ml TNF-α灌流 10 min后 ,乳头肌收缩力分别减小到对照的 91%和 76 % (P均 <0 .0 1) ;2 TNF-α处理后对心肌细胞钙瞬态变化幅度无明显影响 (0 .97± 0 .0 5 vs0 .95± 0 .0 7,P>0 .0 5 ) ;3TNF- α明显抑制肌浆网 Ca2 + - ATPase活性 ,平均抑制率达到 2 0 % ;4 TNF- α拮抗肌浆网 Ca2 + - ATPase对底物中不同水平的 Ca2 +和 ATP的正反应性 ;5TNF- α对肌膜 Ca2 + - ATP酶和 Na+ / K+ - ATP酶活性无明显抑制作用。结论 :TNF- α抑制心肌收缩力的负性肌力作用机制可能部分与心室肌浆网 Ca2 + - ATP酶活性下降有关 ,而与膜上的 Ca2 + - ATP酶和 Na+ / K+ - ATP酶活性无关。Objective: To investigate the mechanism of the negative inotropic effect of tumor necrosis factor- alpha (TNF-α) in cardiomyocytes.Methods:The spectrofluorometric method was used to verify the calcium handling of the single myocyte.The activities of Ca 2+-ATPase of sarcoplasmic reticulum (SR) and the activities of Ca 2+-ATPase and Na +/K +-ATPase of plasma membrane were measured with colorimetric methods.Results:TNF-α at 20 U/ml and 200 U/ml depressed the contractility of ventricular papillary muscle to 91% and 76% of control (P<0.01) respectively,but had no effect on the amplitude of electrically induced calcium transient in single myocyte.TNF-α inhibited the responsiveness of SR Ca 2+ATPase activity to ATP (0.1~4 mmol/L) and Ca 2+ (1~40 μmol/L).TNF-α did not alter the activities of Ca 2+-ATPase and Na +/K +-ATPase of plasma membrane compared with control group.Conclusion:TNF-α decreases the myocardial contractility,at least partly,by inhibiting the activity of SR Ca 2+-ATPase.

关 键 词：肿瘤坏死因子Α 心肌 负性肌力作用 CA^2+-ATP酶 Na^+/K^+-ATP酶 肌浆网 冠心病 心血管疾病 

分 类 号：R331[医药卫生—人体生理学] R54[医药卫生—基础医学]