白细胞介素-2对心肌β-肾上腺素受体作用的调制  

Modulation of interleukin-2 on the positive effect of isoproterenol in the isolated cardiomyocytes

作　　者：王琳琳[1] 夏强[1] 陈莹莹[1] 曹春梅[1] 张雄[1] 

机构地区：[1]浙江大学医学院生理教研室,浙江杭州310031

出　　处：《中国病理生理杂志》2005年第1期63-67,共5页Chinese Journal of Pathophysiology

基　　金：浙江省自然科学基金青年人才专项资金资助(No.RC99038)

摘　　要：目的研究生理浓度白细胞介素-2(IL-2)对β-肾上腺素受体激动剂异丙肾上腺素(ISO)心肌细胞效应的调制作用及其信号途径。方法采用酶解分离的成鼠心室肌细胞模型,用视频跟踪系统测定单个心室肌细胞的收缩幅度、最大收缩速度和最大舒张速度(±dL/dtmax);以Fura-2/AM为钙探针,用细胞内双波长钙荧光系统检测心肌[Ca2+]i的变化。结果①ISO显著增加心肌细胞的收缩幅度和±dL/dtmax,2×103U/L的IL-2预处理15min对心肌细胞的收缩没有影响,但是使心肌细胞对ISO的反应明显降低;②ISO浓度依赖性地增加心肌细胞的钙瞬态值,EC50为(012±001)μmol/L。2×103U/L的IL-2预处理15min对心肌细胞的钙瞬态值没有影响,但是使心肌细胞对ISO的反应曲线显著降低,EC50为(044±006)μmol/L;③20mg/LCTX预处理12h可显著增加心肌细胞的钙瞬态值,2×103U/L的IL-2处理5min可显著降低钙瞬态值;④Forskolin显著增加单个心肌细胞的钙瞬态值,IL-22×103U/L预处理15min后,forskolin增加钙瞬态值的最大效应降低。结论生理浓度的IL-2(2×103U/L)能够显著抑制ISO对单个分离心肌细胞的正性肌力作用和钙瞬态值增高作用。IL-2的调制作用可能是通过抑制Gs蛋白,降低AC的活性来实现的。AIM: To explore the effects and mechanism of interleukin-2 (IL-2) on the positive effect of isoproterenol (ISO) in the isolated rat cardiomyocytes. METHODS: Enzymatically isolated cardiomyocytes were used. Peak twitch amplitude and maximal velocity of shortening/relaxation (±dL/dt_~max ) in the isolated cardiomyocytes were recorded with a microscope coupled to a charge-coupled device camera and [Ca^2+ ]i transients were determined with a fluorometric ratio method by using Fura-2/AM as Ca^2+ indicators. RESULTS: ① ISO increased the peak twitch amplitude and ±dL/dt_~max of the isolated cardiomyocytes. Perfusion for 15 min with IL-2 at 2×103 U/L, which had no effect at all, attenuated the enhancing effect of ISO on the peak twitch amplitude and ±dL/dt_~max . ② ISO increased the [Ca^2+ ]i transients of the single ventricular myocytes in a dose dependent manner and the corresponding EC_~50 values of ISO was (0.12±0.01) μmol/L. Perfusion for 15 min with IL-2 at 2×103 U/L, which had no effect on the ~[Ca^2+ ]i transient at all, attenuated the enhancing effect of ISO and the corresponding EC_~50 was (0.44±0.06) μmol/L. ③ The electrically induced [Ca^2+ ]i transient was significantly increased by pretreatment with 20 mg/L cholera toxin for ~12 h. The elevation of the [Ca^2+ ]i transient induced by cholera toxin was significantly attenuated by 2×103 U/L IL-2. ④ Forskolin (1 μmol/L), the activator of adenyl cyclase, significantly increased the electrically induced [Ca^2+ ]i transient, which was attenuated by IL-2 at 2×103 U/L. CONCLUSION: IL-2 inhibits the positive effect of isoproterenol in the isolated single ventricular myocytes, in which Gs protein and adenyl cyclase are involved. [

关 键 词：心肌 细胞 白细胞介素-2 异丙肾上腺素 

分 类 号：R363[医药卫生—病理学]