钾离子通道的活性状态对蛛网膜下腔注射腺苷抗伤害性作用的影响

目的探讨ATP敏感型钾离子通道的活性状态对鞘内注射腺苷类似物R-phenylisopropyladenosine(R-PIA)抗伤害性作用的影响.方法雄性SD大鼠在苯巴比妥钠麻醉下,蛛网膜下腔留置PE-10导管,测定注药后鼠尾对光热刺激的反应(抗伤害作用).结果蛛网膜下腔注射R-PIA产生剂量依赖性的甩尾时间曲线上移(P＜0.05).蛛网膜下腔注药后10min起效,镇痛时间长达60min.ATP敏感型通道开放剂nicorandil和阻滞剂glibenclamide单独蛛网膜下腔应用无镇痛作用(P＞0.05),但nicorandil明显增强R-PIA的抗伤害性作用,相反glibenclamide明显减弱R-PIA的抗伤害性作用(P＜0.05).结论蛛网膜下腔注射R-PIA可产生明显的剂量依赖性抗伤害作用,此作用受ATP敏感型钾离子通道活性调节.

Effect of adenosine triphosphate-sensitive potassium channel on antinociception of intrathecal adenosine agonist in rats

Objective: To investigate the effect of adenosine triphosphate-sensitive potassium channel (K+ATP) on the antinociception of adenosine agonist R-phenylisopropyladenosine (R-PIA) administered into intrathecal (IT) on conscious rats. Methods: Sprague-Dawley rat was inserted intrathecal catheter (PE-10, 8.5 cm) to the lumbar subarachnoid space under pentobarbital anesthesia. After one week of recovery from surgery, antinociceptive effect was tested by tail-flick latency method after R-PIA injection into IT with K+ATP opener nicorandil or inhibitor glibenclamide. Results: Microinjection of R-PIA into IT produced a significant does- and time-dependent antinociceptive action (P ＜0.05). The intrathecal administration of 5μg nicorandil and 2μg glibenclamide alone did not produce any antinociceptive effect (P ＞0.05), but nicorandil did strengthen the antinociception induced by intrathecal R-PIA,glibenclamide did weaken the antinociception induced by intrathecal R-PIA respectively (P ＜0.05). Conclusions:The present results suggest that adenosine agonist R-PIA administered into IT produce the antinociceptive effect on painful stimulation via K+ATP channel activation at the spinal cord level.