吗啡依赖大鼠不同脑区肌动蛋白及其结合蛋白的表达变化

摘要

Aim To investigate the expression of actin and actin-binding protein p-cofilin in several brain regions of morphine dependent rats. Methods Fourtytwo male SD rats were randomly divided into morphine dependent I week group ( group M1 ), morphine dependent 2 weeks group ( group M2 ) and morphine dependent 4 weeks group ( group M4 ) with 7 animals in each group. Every morphine dependent group had corresponding control group. In morphine dependent group the animals were given intraperitoneally increasing doses of morphine starting from 5, 10, 15, 20.3 0 , 40 , 5 0 mg · kg-1 three times a day for7 days .Rats in control group received the equal volume of saline. In group M2 and group M4 the animals received continuously 50 mg · kg-1 morphine injection once a day for 1 or 3 weeks respectively. Rats were sacrificed by decapitation 5 hours after the last injection. The brain regions including prefrontal cortex, hippocampus, striatum and thalamus were separated and frozen until assay. The expression of actin and actin-binding protein p-cofilin in several brain regions of rats were determined by Western blot. Results Compared with the control group, the ratio of F-actin to C-actin in prefrontal cortex of group M2 and group M4 was upregulated by 53％ ( P ＜0. 05 ) and 102％ ( P ＜0. 01 )respectively. The expression of p-cofilin in prefrontal cortex of group M2 and group M4 was up-regulated by 93％ ( P ＜ 0. 01 ) and 88％ ( P ＜ 0. 01 ) respectively.The ratio of F-actin to G-actin in hippocampus of group M4 was up-regulated by 94％ ( P ＜ 0. 01 ). The expression of p-cofilin in hippocampus of group M2 and group M4 was up-regulated by 45％ ( P ＜ 0. 05 ) and 30％ ( P ＜ 0. 05 )respectively. The expression of p-cofilin in striatum of group M2 and group M4 was downregulated by 25％( P ＜ 0. 05 )and 30％( P ＜0. 05 )respectively. Conclusion Chronic morphine treatment can induce the development of morphine dependence,which accompanies with actin rearrangments in the brain of rats in time-dependent and brain region-dependent way.%目的 研究吗啡依赖大鼠不同脑区肌动蛋白及其结合蛋白p-cofilin的表达变化.方法 42只♂ SD大鼠,随机分为吗啡依赖1周组(M1组)、2周组(M2组)和4周组(M4组),各依赖组均设对照,每组7只.吗啡依赖组采用剂量递增法腹腔注射吗啡,每日3次,连续7 d,日剂量按5,10,15,20,30,40,50 mg·kg-1逐日递增,对照组给与等体积的生理盐水.M2和M4组大鼠继续分别给予50 mg·kg-1盐酸吗啡,每天1次,连续注射1或3周.在最后一次给药后5 h断头处死大鼠,迅速分离前额叶皮质、海马、纹状体和丘脑.Western blot检测吗啡依赖大鼠不同脑区肌动蛋白及其结合蛋白的表达变化.结果 与对照组相比,M2和M4组大鼠前额叶皮质内F-actin/G-actin比值分别上调53%(P<0.05)和102%(P<0.01);M2和M4组大鼠前额叶皮质内p-cofilin表达量分别上调93% (P<0.01)和88%(P<0.01).M4组大鼠海马中F-actin/G-actin比值上调94%;M2和M4组大鼠海马中p-cofilin蛋白表达量分别上调45%(P<0.05)和30%(P<0.05).M2和M4组大鼠纹状体内p-cofilin的蛋白表达量分别下调25%(P<0.05)和30%(P<0.05).结论 长期吗啡处理可诱导大鼠形成依赖,伴随着依赖相关脑区肌动蛋白重构,并呈现脑区特异性和时间依赖性.