异丙酚和地卓西平马来酸盐对电休克后抑郁模型大鼠学习记忆和Tau蛋白过度磷酸化的影响  

Effects of Propofol and Dizocilpine Maleate on the Cognitive Abilities and the Hyperphosphorylation of Tau Protein of Rats after the Electroconvulsive Therapy

作　　者：刘超[1] 闵苏[1] 魏珂[1] 刘东[2] 董军[1] 罗洁[1] 黎平[1] 刘小滨[1] 

机构地区：[1]重庆医科大学附属第一医院麻醉科,重庆400016 [2]天津医科大学第二医院神经外科,天津300211

出　　处：《中国医学科学院学报》2012年第4期324-329,共6页Acta Academiae Medicinae Sinicae

基　　金：国家自然科学基金(30972831)~~

摘　　要：目的观察异丙酚和地卓西平马来酸盐(MK-801)对电休克(ECT)后抑郁模型大鼠学习记忆和Tau蛋白过度磷酸化的影响。方法按析因设计干预因素,即ECT(2水平:无处置和1个疗程ECT)和药物(3水平:腹腔注射生理盐水、异丙酚和MK-801),采用Morris水迷宫检测认知能力,高效液相色谱法检测谷氨酸(Glu)含量,Westernblot检测Tau5、PHF-1(pSer396/404)、AT8(pSer199/202)、12E8(pSer262)在大鼠海马中的表达。结果异丙酚、MK-801及ECT均可造成大鼠学习记忆障碍,ECT可明显增加海马中Glu浓度,异丙酚可降低海马中Glu浓度,MK-801对海马中Glu浓度无明显影响。ECT可增加海马中磷酸化Tau蛋白的表达,异丙酚和MK-801可减少海马中磷酸化Tau蛋白的表达。结论异丙酚和MK-801可能是通过降低海马Glu浓度,减缓Tau蛋白的磷酸化程度,进而改善认知能力。Objective To explore the effects of propofol and dizocilpine maleate （ MK-801 ） on the cognitive abilities the hyperphosphorylation of Tau protein of rats after the electroeonvulsive therapy. Methods Two intervention factors including electroconvulsive shock therapy （ECT） （two levels： not applied and one treatment course） and drug intervention （three levels： intravenous saline, intravenous MK-801, and intrave- nous propofol）. The morris water maze test started within 1 day after ECT to evaluate the learning-memory. Theglutamate level in the hippocampus of rats was determined by high-performance liquid chromatography. The Tau protein that includes Tau5 （ total Tau protein）, PHF-1 （ pSer396/404 ） , AT8 （ pSer199/202 ） , and 12E8 （ pSer262 ） in the hippoeampus of rats was determined using Western blotting. Results Propofol, MK-801, and ECT could induce the impairment of learning-memory in depressed rats. The electroconvulsive shock significantly up- regulated the glutamate level, which was reduces by the propofol. The ECT up-regulated the hyperphosphoryla- tion of Tau protein in the hippoeampus of depressed rats, which was reduced by propofol and MK-801. Con- clusion Both propofol and MK-801 could protect against the impairment of learning-memory and reduce the hyperphosphorylation of Tau protein induced by ECT in depressed rats.

关 键 词：异丙酚 N-甲基-D-天门冬氨酸受体拮抗剂 电休克 学习记忆 TAU蛋白 

分 类 号：R614.24[医药卫生—麻醉学]