钾离子通道TASK-1、TASK-3在大鼠脑干的表达与睡眠呼吸暂停的关系

Relationship between TWlK-related acid-sensitive K^+ channel-1 and TWIK-related acid-sensitive K^+ channel-3 expression and the occurrence of central sleep apnca:experiment with rats

目的探讨钾离子通道 TASK-1、TASK-3在大鼠睡眠呼吸暂停发生中的可能作用。方法对自由活动的 SD 大鼠进行睡眠呼吸监测。采用 Western 印迹的方法检测不同大鼠脑干TASK-1和 TASK-3的蛋白表达水平,并分析其与睡眠呼吸暂停指数的相关性。建立持续性和间歇性缺氧大鼠模型,分析缺氧对 TASK-1和 TASK-3表达的影响。结果正常 SD 大鼠总自发呼吸暂停(SP)指数、NREM 期自发呼吸暂停指数与脑干中 TASK-1蛋白的表达量成正相关(r 值分别为0.547,0.601,均 P<0.01),而叹息后呼吸暂停(PS)指数与 TASK-1表达量无关。自发呼吸暂停指数和叹息后呼吸暂停指数均与 TASK-3的表达量无相关性(P>0.05)。间歇性缺氧伴高碳酸血症可以使TASK-1、TASK-3 在脑干中的表达增加。结论 TASK-1在大鼠呼吸中枢表达量的增加可能参与了睡眠呼吸暂停的发生。间歇性缺氧伴高碳酸血症可上调 TASK-1、TASK-3的表达。

Objective To investigate the role of the TWIK-related acid-sensitive K^＋ channel-1 （TASK-1） in the occurrence of sleep apnea. Methods Brain and muscle electrodes were put on 27 SD rats to monitor the apneic episodes. Then the rats were killed with their brains taken out. Western blotting was used to examine the expression of TASK-1 as well as its family member TASK-3 in the brainstem. Another 32 rats were randomly divided into 3 groups： intermittent hypercapnic hypoxia （IHH） group （n = 14, undergoing IHH 2 hours a day for 14 days）, continuous hypoxia （CH） group （n =6, undergoing CH for 2 hours everyday for 14 days）, and normal control group （n = 10）. On the day 15 the rats were killed with venous blood samples collected to undergo blood routine examination and brainstem samples collected to undergo Western blotting to measure the expression of TASK-1 and TASK-3. The relationship between TASK-1 and TASK-3 expression and the occurrence of central sleep apnea was analyzed. Results In the normal rats the spontaneous apnea index （SPAI） was positively correlated with the protein expression of TASK-in the brainstem and the ratio of the TASK-1 protein expression to the TASK-3 protein expression （ r = 0. 547 and 0. 406 respectively, beth P 〈 0.05 ）. However, the post-sign apnea index （PSAI） was not correlated with the TASK-1 protein expression （P = 0. 986 ）, and beth the SPAI and PSAI were not correlated with the TASK-3 protein expression （ P = 0. 986 and 0. 916 respectively）. Only the SPAI in the non-rapid eye movement, stage was positively correlated with the TASK-1 protein expression and the ratio of TASK-1 protein expression to TASK-3 protein expression （ r = 0.601, 0. 523 respectively, beth P 〈 0.01 ）. The TASK-1 protein expression of the IHH group was significantly higher than those of the CH group and normal control group （ P =0. 032 and 0.004 respectively）. The TASK-3 protein expression of the IHH group was significantly higher than that of the CH group （ P = 0. 005 ）. There were no significant differences in the TASK-1 protein expression and that of TASK-3 between the CH group and the normal control group （beth P 〉 0.05）. Conclusion TASK-1 may play an important role in spontaneous sleep apnea.