慢性吗啡耐受大鼠脑内P糖蛋白的表达及意义  

Expression and significance of P-glycoprotein in rats brain of chronic morphine tolerant

作　　者：王淼[1] 许学兵[2] 佘守章[3] 

机构地区：[1]绍兴第二医院,浙江绍兴312000 [2]广东省第二人民医院,广东广州510317 [3]广州医科大学附属第一人民医院,广东广州510180

出　　处：《浙江实用医学》2014年第3期157-159,232,共4页Zhejiang Practical Medicine

摘　　要：目的观察大鼠慢性吗啡耐受过程中大脑皮质毛细血管内皮细胞P糖蛋白的变化及意义。方法雄性SD大鼠,随机分为3组(n=6):慢性吗啡耐受组、生理盐水组和空白对照组。吗啡耐受组皮下注射10mg/kg的吗啡。生理盐水组皮下注射10mL/kg的生理盐水。空白对照组则不予任何处理。各组每天重复用药两次,上午8点钟和下午6点钟,连续7天给药。测定大鼠吗啡耐受形成的最大镇痛百分率(MPE%),采用免疫组化方法观察大鼠脑内皮质毛细血管内皮细胞P糖蛋白阳性面积的表达情况。结果吗啡耐受组大鼠在第1天的MPE%为(82.50±26.39)%,第3天、第5天、第7天分别下降至(68.33±27.92)%、(46.17±21.50)%和(23.17±15.41)%,与生理盐水组和空白对照组比较差异有统计学意义(P<0.05)。第7天吗啡耐受组P糖蛋白阳性面积为(0.82±0.04)%;生理盐水组P糖蛋白阳性面积为(0.53±0.01)%;空白对照组P糖蛋白阳性面积为(0.31±0.08)%,吗啡耐受组与生理盐水组和空白对照组比较,差异有统计学意义(P<0.05)。结论产生慢性吗啡耐受后,大鼠大脑皮质毛细血管内皮细胞P糖蛋白阳性面积大量表达,而生理盐水组和空白对照组显示不明显,本研究初步表明P糖蛋白参与吗啡耐受的发生机制。Objective To investigate the change of brain P-glycoprotein in the development of morphine tolerance in rats .Methods Male adult SD rats were randomly divided into three groups ：group morphine tolerance received morphine 10mg/kg S .C;group saline received normal saline 10mL/kg S .C .group blank received blank control .changes in tail flick latency（TFL）were expressed as percentage of maximal possible effect （MPE% ） .The change of brain P-glycoprotein response to chronic morphine tolerance were examined by immunohistochemistry .Results In group morphine tolerance MPE% was 82 .50% on the 1st day and gradually decreasing on the 3rd and 5th day and became 23.17% on the 7th day signifying full development of morphine tolerance .group morphine tolerance exhibited significant difference when compared to group saline and group blank （ P〈0.05） .In group saline the P-glycoprotein positive area percentage was 0.53% on the 7th day ,in group blank the P-glycoprotein positive area percentage was 0.31% on the 7th day but in group morphine tolerance the P -glycoprotein positive area percentage was significantly more than in group saline and group blank on the 7th day （ P〈0.05） .Conclusions Chronic morphine exposure appears to increase P -glycoprotein in rat brain .induction of P-glycoprotein may be one mechanism involved in the development of morphine tolerance .

关 键 词：吗啡耐受 脑毛细血管内皮细胞 P糖蛋白 

分 类 号：R96[医药卫生—药理学]