低氧后心肌钙瞬变变化与β-肾上腺素受体脱敏的关系  

β-adrenoceptor desensitization and changes of calcium transient in rat ventricular myocytes following chronic hypoxia

作　　者：裴建明[1] 王跃民[1] 马恒[1] 毕辉[1] 朱妙章[1] 

机构地区：[1]第四军医大学生理学教研室,陕西西安710032

出　　处：《中国病理生理杂志》2003年第4期455-459,共5页Chinese Journal of Pathophysiology

基　　金：第四军医大学创新工程重点项目 (CX0 1F0 0 1);全军医药卫生科研基金军队"十五"计划课题项目 ( 0 1MB12 9)

摘　　要：目的 :慢性低氧时 ,心脏对 β -肾上腺素受体激动的反应出现脱敏现象 ,细胞内钙 [Ca2 +]i 瞬变的幅度降低、时程延长 ,本研究观察上述变化在低氧时发生和发展的时间过程和对应关系。方法 :在年龄对等的正常及慢性低氧 1d、3d、1周、2周、3周、4周和 8周的大鼠 ,分别分离正常及慢性低氧条件下的心室肌细胞 ,以Fura - 2为[Ca2 +]i 的指示剂 ,用光谱荧光法测定心肌细胞的 [Ca2 +]i 瞬变及其对心肌 β -受体激动后反应的变化。 结果 :在低氧 1d、3d、1周等时间内 ,电刺激引起的 [Ca2 +]i瞬变、咖啡因引起的 [Ca2 +]i瞬变及电刺激引起的 [Ca2 +]i 瞬变对 β-受体激动剂异丙肾上腺素的增加反应无明显变化 ;在低氧 2周以上时 ,电刺激引起的 [Ca2 +]i 瞬变的幅度开始降低 ,而时程开始延长 ,其对异丙肾上腺素的反应也开始降低。咖啡因引起的 [Ca2 +]i 瞬变幅度也开始降低 ;在低氧 3周和 4周时 ,上述变化程度逐渐加重 ;在低氧 8周时各参数的变化有所恢复 ,但与 4周时的变化程度无明显差异。结论 :低氧 2 - 4周时 ,心脏的 β -肾上腺素受体发生脱敏现象 ,脱敏的机制与 3种调节 [Ca2 +]i 瞬变的蛋白质 :L -型钙通道、ryanodine受体操纵的钙通道和钙泵等活性的降低有关 ,后者也可能是低氧时心脏功能降低的重要机制。?AIM: The present study was to investigate the time course of β-adrenoceptor desensitization and changes in the calcium transient in rat ventricular myocytes following chronic hypoxia. METHODS: With the spectrofluorometric method, the intracellular calcium( i) transient and its response to β-adrenoceptor stimulation were determined in the single right ventricular myocytes, loaded with Fura-2.RESULTS: After 2-3 weeks of chronic hypoxia, the amplitudes of electrically induced i transient and caffeine-induced i transient started to decrease and the duration of i transient prolonged. The enhanced electrically induced i transient evoked by isoprotrenol was also decreased. After 3 or 4 weeks of chronic hypoxia, these changes aggravated gradually. After 8 weeks of chronic hypoxia, the changes of all these parameters were convalescent, meanwhile there was no significant difference compared with that of 4 weeks group. CONCLUSIONS: After 2-4 weeks of chronic hypoxia, the β-adrenoceptor desensitization occurs, the underlying mechanism is related to the decreased function of L-type of calcium channel, ryanodine receptor-operated calcium channel and calcium ATPase, which is responsible for the decreased cardiac functionl. At 8 weeks of hypoxia, the heart is in adaptation and compensatory process.

关 键 词：低氧 心肌钙 瞬变变化 Β-肾上腺素受体 脱敏 

分 类 号：R331.31[医药卫生—人体生理学]