急、慢性吗啡处理对大鼠大脑皮层tau蛋白和神经微丝磷酸化水平的影响  

Phosphorylation of tau and neuroflament in prefrontal cortex of rat brain after acute and chronic morphine administration

作　　者：曹铭辉[1] 纪风涛[1] 何惠燕[2] 刘付宁[1] 梁建军[1] 刘玲[1] 

机构地区：[1]中山大学附属第二医院麻醉科,广州广东510120 [2]中山大学附属第二医院供应中心,广州广东510120

出　　处：《中国病理生理杂志》2010年第9期1718-1721,共4页Chinese Journal of Pathophysiology

基　　金：广东省自然科学基金资助项目(No7001595)

摘　　要：目的:观察急、慢性吗啡处理对大鼠大脑皮质细胞骨架蛋白磷酸化水平的影响,探讨吗啡导致细胞周期依赖性蛋白激酶-5(cyclin dependent kinase-5,CDK5)过度表达与细胞骨架蛋白过度磷酸化的关系。方法:雄性SD大鼠40只,随机均分为急性对照组、急性吗啡处理组、慢性对照组、慢性吗啡处理组。急性吗啡处理组腹腔注射吗啡30mg/kg1次,慢性吗啡处理组腹腔注射吗啡10mg/kg,每天2次(时间8:00、20:00)共10d。采用免疫印迹法测定大鼠大脑皮质tau蛋白和神经微丝的磷酸化水平及CDK5、p35表达水平。结果:(1)与急性对照组比较,急性吗啡处理组tau蛋白和神经微丝磷酸化水平升高,CDK5的表达增加;(2)与慢性对照组比较,慢性吗啡处理组tau蛋白和神经微丝磷酸化水平升高,CDK5的表达无明显变化;(3)与急性吗啡处理组比较,慢性吗啡处理组tau蛋白和神经微丝蛋白磷酸化水平降低;(4)各组间p35表达水平无明显改变。结论:急、慢性吗啡处理可导致大鼠大脑皮质tau蛋白和神经微丝的异常过度磷酸化,但这种变化可能与CDK5的过度表达无关。AIM： To investigate the phosphorylation of cytoskeletal protein in the rat brain after acute and chronic morphine administration,and to determine the relationship between morphine-induced cyclin-dependent kinase-5 （ CDK5） over-expression and herphosphorylation of cytoskeletal protein. METHODS： Forty male SD rats,weighing 220-250 g,were randomly divided into acute control group,acute morphine administration group,chronic control group and chronic morphine administration group （ 10 rats in each group） . The rats in acute morphine administration group received intraperitoneal injection of morphine at dose of 30 mg/kg. The rats in chronic morphine administration group were injected with morphine intraperitoneally twice a day （ 10 mg/kg at time 8： 00 and 22： 00,respectively） for 10 days. The rats in acute control group and chronic control group received equi-volume of normal saline in the same way. Two hours after the last injections,the rats were sacrificed and the prefrontal cortex was collected for detecting the phosphorylation levels of neuronal cytoskeletal proteins,CDK5 and p35 by the method of immunoblotting. RESULTS： （ 1） In acute morphine administration group,the level of phosphorylated tau at the sites of Thr205,Ser404 and phosphorylated neurofilament was increased. The level of CDK5 was also increased. （ 2） In chronic morphine administration group,the levels of phosphorylated tau and phosphorylated neurofilament were enhanced,but the level of CDK5 was not changed markedly. （ 3） Compared to acute morphine administration group,the levels of phosphorylated tau and phosphorylated neurofilament were decreased in chronic morphine administration group. （ 4） The level of p35 was unchanged in all groups. CONCLUSION：Acute or chronic morphine administration induces hyperphosphorylation of tau and neurofilament in the rat cortex,and the changes may be not relevant to over-expression of CDK5.

关 键 词：吗啡 TAU蛋白质类 神经微丝 过度磷酸化 CDK5 

分 类 号：R749.61[医药卫生—神经病学与精神病学]