氯胺酮的快速抗抑郁作用与大鼠缰核内βCaMKⅡ表达下调的关系  

Rapid antidepressant effect of ketamine associated with down-regulation of βCaMKⅡin habenular of depression rats

作　　者：李倩倩[1] 周国霞[1] 蒋克泉[1] 朋立超[1] 

机构地区：[1]复旦大学附属上海市第五人民医院麻醉科,上海200240

出　　处：《复旦学报（医学版）》2015年第3期368-372,共5页Fudan University Journal of Medical Sciences

基　　金：上海市卫生局面上基金(20114218)~~

摘　　要：目的探讨氯胺酮抗抑郁作用的潜在分子机制,以及对抑郁大鼠缰核β钙/钙调素依赖蛋白激酶Ⅱ(βcalcium/calmolulin-dependent protein kinase typeⅡ,βCaMKⅡ)和谷氨酸受体1(glutamic acid receptor 1,GluR1)分子表达的影响。方法成年Wistar大鼠11只(正常组),Wistar-Kyoto(WKY)大鼠22只随机分为抑郁组和氯胺酮(Ket组)。Ket组给予氯胺酮10mg/kg腹腔注射,抑郁组和正常组则腹腔注射等容量的生理盐水,连续3天。第4天行糖水偏好试验,测定大鼠的糖水偏好程度。第5天行开场试验及强迫游泳试验,测定大鼠的行为。行为学试验结束后0.5h取大鼠脑组织,Western blot检测大鼠缰核βCaMKⅡ和GluR1的表达。结果抑郁组与正常组大鼠相比,糖水百分比降低,站立次数减少,强迫游泳不动时间显著增加,缰核βCaMKⅡ的表达水平升高(P<0.05);Ket组与抑郁组大鼠相比,糖水百分比升高,站立次数增加,强迫游泳不动时间缩短,缰核βCaMKⅡ的表达水平降低(P<0.05),GluR1的表达无变化。结论氯胺酮具有快速的抗抑郁作用,其机制可能与缰核βCaMKⅡ的表达下调有关。Objective To investigate the antidepressant effects of ketamine,and the expressions of β calcium/calmolulin-dependent protein kinase type Ⅱ （βCaMKⅡ） and glutamic acid receptor 1 （GluR1） in habenular in depression rats.Methods Twenty-two adult Wistar-Kyoto （WKY） rats were randomly assigned to saline control group （depression group） and ketamine group （Ket group）,and 11 Wistar rats were taken as the normal group.Rats in Ket group were intraperitoneally injected with ketamine of 10 mg/kg,and those in normal group and depression group were administrated with the same amount of normal saline for 3 days.On the 4th day,sucrose preference test was adopted to measure the degree of sugar preference of rats.On the 5th day,open field test and forced swimming test were used to explore the behavior of rats.The habenular was obtained half an hour after the behavior tests,and the expressions of βCaMKⅡ and GluR1 were determined by Western blot.Results The results showed that sugar percentage was decreased,thenumber of standing was reduced in open field test,the immobility time was increased in the forced swimming test,and the levels of βCaMKⅡ in habenula were elevated （P ＜ 0.05） in depression group in comparison with normal rats.While sugar percentage was increased,the number of standing was increased in open field test,the immobility time was shortened in the forced swimming,the levels of βCaMKⅡ in habenula were reduced （P＜0.05）,and the levels of GluR1 unchanged （P＞0.05） in Ket group compared with the depression rats.Conclusions Application of ketamine in depression rats could reduce depressive symptoms,and this may be associated with the downregulation of βCaMKⅡ in habenular of depression rats.

关 键 词：抑郁症 氯胺酮 βCaMKⅡ GLUR1 大鼠 

分 类 号：R964[医药卫生—药理学]