脊髓糖皮质激素受体在吗啡耐受大鼠PI3K／Akt信号通路中的作用  

Role of spinal glucocorticoid receptor in PI3K/Akt signaling pathway in rats with morphine tolerance

作　　者：陈怡[1] 于泳浩[1] 孙云菲[1] 王晓娜[1] 王国林[1] 

机构地区：[1]天津医科大学总医院麻醉科,300052

出　　处：《中华麻醉学杂志》2011年第10期1220-1223,共4页Chinese Journal of Anesthesiology

基　　金：天津医科大学科学基金（2008ky33）;天津医科大学重点学科基金（Yjzhd0908）

摘　　要：目的探讨脊髓糖皮质激素受体（GR）在吗啡耐受大鼠磷脂酰肌醇-3激酶，蛋白激酶B（P13K／Akt）信号通路中的作用。方法健康雄性SD大鼠，8～10周龄，体重300～350g，取鞘内置管成功的大鼠40只，采用随机数字表法，将大鼠随机分为4组（n=10）：对照组（C组）鞘内注射生理盐水10μl；吗啡耐受组（M组）鞘内注射吗啡10μg；地塞米松组（GR激动剂，DEX组）鞘内注射地塞米松4μg，30min后注射吗啡10μg；RU38486组（GR阻断剂，R组）鞘内注射RU384862μg，30min后注射吗啡10μg。注射药物容量均为10μl，2次／d，连续7d。于每天第1次鞘内给药前和鞘内给药结束后1d测定甩尾潜伏期，计算最大抗伤害效应百分比（MPAE），最后一次甩尾潜伏期测定结束后，取脊髓背角组织，测定P13K、Caspase．3的表达水平和Akt活性。结果M组、DEX组和R组发生了吗啡耐受，C组未发生吗啡耐受。与C组比较，M组脊髓背角Akt活性降低，P13K表达下调，Caspase．3表达上调（P〈0．01）；与M组比较，DEX组MPAE和Akt活性降低，P13K表达下调，Caspase-3表达上调，R组MPAE和Akt活性升高，P13K表达上调，Caspase-3表达下调（P〈0．05）。结论脊髓GR可通过抑制P13K／Akt信号通路参与吗啡耐受的形成。Objective To investigate the role of spinal glucocorticoid receptors （GR） in phosphoinositide 3-kinase/protein kinase B （PI3K/Akt） signal pathway in rats with morphine tolerance. Methods Forty healthy male SD rats aged 8-10 weeks weighing 300-350 g in which intrathecal （IT） catheters were successfully implanted without complication were randomly divided into 4 groups （n = 10 each） ：control group（group C） received IT injection of normal saline 10 μl twice a day for 7 consecutive days; morphine tolerance group（group M） received IT injection of morphine 10 μg twice a day for 7 consecutive days; dexamethasone （a GR agonist）group（group DEX） received IT injection of dexamethasone 4μg 30 min before IT injection of morphine, twice a day for 7 consecutive days;RU38486（a GR blocker）group （group R） received IT injection of RU38486 2μg 30 min before IT injection of morphine, twice a day for 7 consecutive days. Tail-flick test was measured once a day after first IT administration and 1 d after the end of IT administration, and the percentage of maximum possible antinociceptive effect （MPAE） was cacnlated. After the last measurem of tail-flick test, the spinal dorsal horns were removed for determination of PI3K, Caspase-3 expression and Akt activity. Results Morphine tolerance developed in groups M, DEX and R, but did not develop in group C. Compared with group C, Akt activity was decreased, PI3K expression was downregulated and Caspase-3 expression was up-regulated in group M （ P 〈 0.05 ）. Compared with group M, MPAE and Akt activity were decreased, PI3K expression was down-regulated and Caspase-3 expression was up-regulated in group DEX, and MPAE and Akt activity were inecreased, PI3K expression was up-regulated and Caspase-3 expression was down-regulated in group R （P 〈 0.05）. Conclusion Spinal cord GR is involved in morphine tolerance by inhibiting PI3K/Akt signal pathway.

关 键 词：药物耐受性 吗啡 受体 糖皮质激素 1-磷脂酰肌醇3-激酶 蛋白质丝氨酸 苏氨酸激酶 脊髓 

分 类 号：R96[医药卫生—药理学]