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.
出处
《中国医学科学院学报》
CAS
CSCD
北大核心
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)~~
