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脊髓蛋白激酶C#alpha#和#gamma#亚型在吗啡依赖和戒断反应中的不同作用

曹君利, 丁海雷, 何建华, 张励才, 王俊科, 曾因明

中国医科大学第一临床学院附属第一医院麻醉科.辽宁,沈阳 110001；江苏省麻醉医学研究所,江苏省麻醉学重点实验室江苏,徐州 221002

摘要

在大鼠吗啡依赖和戒断模型上,采用行为学、免疫组织化学和Western blot方法观察鞘内应用蛋白激酶C(protienkinase C,PKC)抑制剂chelerythrine chloride(CHE)对吗啡依赖大鼠纳洛酮催促戒断反应、脊髓Fos蛋白表达和脊髓神经元胞膜和胞浆PKC#alpha#、#gamma#表达的影响,以探讨不同亚型PKC在吗啡依赖和戒断反应中的作用。结果表明,鞘内注射CHE能明显减轻吗啡戒断症状的评分和吗啡戒断引起的痛觉异常,抑制吗啡戒断期间脊髓Fos蛋白表达的增加;吗啡依赖可引起脊髓神经元PKC #alpha#和#gamma#表达的上调和转位;吗啡戒断期间存在明显的且可被鞘内注射CHE抑制的PKC#alpha#转位,但未观察到明显的PKC #gamma#转位。上述结果提示,脊髓PKC表达上调和转位可能参与吗啡依赖的形成和戒断反应的表达,且PKC #alpha#和#gamma#亚型在吗啡依赖和戒断反应中的作用存在差异。

关键词： 吗啡依赖; 戒断综合征; 脊髓; 蛋白激酶C; 转位; 痛觉异常

Different roles of the spinal protein kinase C #alpha# and #gamma# in morphine dependence and naloxone--precipitated withdrawal

Cao Junli, Ding Hailei, He Jianhua, Zhang Licai, Wang Junke, Zeng Yinming

Department of Anesthesiology, Affiliated Hospital of First Clinical College, China Medical University.Shenyang 110001,Liaoning；China

Abstract

Our previous studies showed that spinal neurons sensitization was involved in morphine withdrawal response. This study was to investigate the roles of spinal protein kinase C (PKC) #alpha#，#gamma# in morphine dependence and naloxone-precipitated withdrawal response. To set up morphine dependence model, rats were subcutaneously injected with morphine (twice a day, for 5 d). The dose of morphine was 10 mg/kg in the first day and was increased by 10 mg/kg each day. On day 6, 4 h after the injection of morphine (50 mg/kg), morphine withdrawal syndrome was precipitated by an injection of naloxone (4 mg/kg, ip). Chelerythrine chloride (CHE), a PKC inhibitor, was intrathecally injected 30 min before the administration of naloxone. The scores of morphine withdrawal symptom and morphine withdrawal-induced allodynia were observed. One hour after naloxone-precipitated withdrawal, Fos protein expression was assessed by immunohistochemical analysis and western blot was used to detect the expression of cytosol and membrane fraction of PKC #alpha# and #gamma# in the rat spinal cord. The results showed that intrathecal administration of CHE decreased the scores of morphine withdrawal, attenuated morphine withdrawal-induced allodynia and also inhibited the increase of Fos protein expression in the spinal cord of morphine withdrawal rats. The expression of cytosol and membrane fraction of PKC #alpha# was significantly increased in the spinal cord of rats with morphine dependence. Naloxone-precipitated withdrawal induced PKC #alpha# translocation from cytosol to membrane fraction, which was prevented by intrathecal administration of CHE. During morphine dependence, not naloxone-precipitated withdrawal, PKC #gamma# in the spinal cord translocated from cytosol to membrane fraction, and intrathecal administration of CHE did not change the expression of PKC #gamma# in the spinal cord of naloxone-precipitated withdrawal rats. It is suggested that up-regulation and translocation of PKC in the spinal cord contribute to morphine dependence and naloxone-precipitated withdrawal in rats and that PKC #alpha# and #gamma# play different roles in the above-mentioned effect.

Key words: morphine dependence;substance withdrawal syndrome;Spinal cord;Protein kinase C;translocation;allodynia

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引用本文：

曹君利, 丁海雷, 何建华, 张励才, 王俊科, 曾因明. 脊髓蛋白激酶C#alpha#和#gamma#亚型在吗啡依赖和戒断反应中的不同作用[J]. 生理学报 2005; 57 (2): .

Cao Junli, Ding Hailei, He Jianhua, Zhang Licai, Wang Junke, Zeng Yinming. Different roles of the spinal protein kinase C #alpha# and #gamma# in morphine dependence and naloxone--precipitated withdrawal. Acta Physiol Sin 2005; 57 (2): (in Chinese with English abstract).