纳洛酮减弱白细胞介素-2对大鼠心肌的抑制作用

目的 :研究白细胞介素 - 2 (IL - 2 )的心脏作用并探讨其相关机制。方法 :采用视频跟踪系统测定大鼠单个心室肌细胞的收缩 ;细胞内双波长钙荧光系统检测细胞内游离钙离子浓度 ;应用 Langendorff灌流装置 ,观察 IL - 2对完整心脏收缩力学的影响。结果 :与对照相比 ,IL - 2 (5、5 0 U/ml)显著抑制单个心室肌细胞的收缩幅度 [(74 .95±4 .79vs98.0 9± 5 .0 2 ) % ,(6 4.30± 5 .2 4 vs97.38± 4 .0 5 ) % ]、最大收缩速度 [(70 .2 3± 4 .85 vs98.0 9± 5 .4 6 ) % ,(6 1.15± 5 .2 0 vs97.38± 6 .85 ) % ]、最大舒张速度 [(71.2 2± 4 .79vs98.32± 6 .0 8) % ,(6 8.16± 5 .2 4 vs97.5 5±5 .0 0 ) % ]和舒张末细胞长度 [(88.2 8± 5 .84 vs97.95± 5 .5 2 ) % ,(84 .18± 6 .5 2 vs98.94± 6 .76 ) % ];IL- 2 (5、5 0 U/ml)显著降低电刺激诱导的心肌细胞内钙瞬变幅度 [(74 .94± 4 .90 vs98.0 9± 3.74 ) % ,(71.0 0± 5 .2 8vs97.38±5 .5 2 ) % ],使舒张末钙水平升高 [(113.91± 5 .93vs10 0 .10± 3.0 2 ) % ,(119.0 9± 7.12 vs10 0 .5 2± 6 .0 0 ) % ]。阿片受体阻断剂纳洛酮 (10 nmol/L)可阻断 IL- 2对心肌细胞收缩和细胞内钙的作用。在离体心脏 ,与对照相比 ,IL- 2 (5 0U/ml)可显著降低左心室

Naloxone for attenuation of interleukin-2-induced myocardial depression in rat hearts

OBJECTIVE: To investigate the cardiac effect of interleukin-2 (IL-2) and to explore the underlying mechanism. METHODS: The video tracking system and spectrofluorometric method were used to measure the cell contraction and intracellular calcium. Fura-2/AM was used as a calcium fluorescence probe. Langendorff perfusion technique was used to determine the effect of IL-2 on the intact heart. RESULTS: Compared with the control group, IL-2 5 U/ml, 50 U/ml significantly decreased cell contraction amplitude [(74.95+/-4.79) vs (98.09+/-5.02)%, (64.30+/-5.24) vs (97.38+/-4.05)%], peak velocity of cell shortening [(70.23+/-4.85)% vs (98.09+/-5.46)%, (61.15+/-5.20)% vs (97.38+/-6.85)%], peak velocity of cell relengthening [(71.22+/-4.79)% vs (98.32+/-6.08)%, (68.16+/-5.24)% vs (97.55+/-5.00)%] and end- diastolic cell length [(88.28+/-5.84)% vs (97.95+/-5.52)%, (84.18+/-6.52)% vs (98.94+/-6.76)%]. IL-2 (5 U/ml, 50 U/ml) also markedly inhibited intracellular calcium transient [(74.94+/-4.90)% vs (98.09+/-3.74)%,(71.00+/-5.28)% vs (97.38+/-5.52)%], and elevated end-diastolic calcium level of ventricular myocytes [(113.91+/-5.93)% vs (100.10+/-3.02)%, (119.09+/-7.12)% vs (100.52+/-6.00)%], which were attenuated by the opioid receptor antagonist naloxone (Nal,10 nmol/L). In the isolated perfused rat heart,when compared with the control group, IL-2 50 U/ml markedly decreased left ventricular developed pressure [(79.91+/-2.18) vs (93.84+/-2.94)mmHg], maximal rate of rise of left ventricular pressure [(2370.7358.29) vs (2591.50+/-62.81)mmHg] maximal rate of fall of left ventricular [-(1460.95+/-38.6) vs -(1634.24+/-54.05) mmHg/s] and heart rate [(217.35+/-10.56) vs (244.52+/-11.23) beats/min], but increased left ventricular end-diastolic pressure (11.44+/-1.02 vs 9.23+/-0.46). Pretreatment with Nal (10 nmol/L) antagonized the cardiac depression and left ventricular end-diastolic pressure elevation induced by IL-2. CONCLUSION: The cardiac effect of IL-2 is mediated by opioid receptors on the membrane of cardiomyocytes.