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氯胺酮復(fù)合異丙酚麻醉對抑郁大鼠電休克后海馬谷氨酸受體亞基1和亞基2的影響

發(fā)布時間:2019-01-12 11:06
【摘要】:目的評價小劑量氯胺酮復(fù)合異丙酚麻醉對抑郁大鼠電休克(electroconvulsive therapy,ECT)后海馬谷氨酸受體亞基1(glutamate receptor subunit 1,Glu R1)及亞基2(glutamate receptor subunit 2,Glu R2)的影響。方法健康成年雄性SD大鼠32只,采用孤養(yǎng)與慢性輕度不可預(yù)見性應(yīng)激(chronic unpredictable mild stress,CUMS)建立抑郁模型,建模成功后隨機(jī)分為抑郁組(A組)、ECT組(B組)、ECT+異丙酚組(C組)和ECT+異丙酚+氯胺酮組(D組)4組,每組8只;另取8只正常大鼠作為對照組。對照組不做任何處理;A組腹腔注射生理鹽水8 m L/kg后給予偽ECT處理;B、C、D組分別腹腔注射生理鹽水8 m L/kg、異丙酚80 mg/kg、異丙酚80 mg/kg+氯胺酮10 mg/kg后行ECT處理,上述處理連續(xù)7 d。分別采用糖水偏好實驗和Morris水迷宮實驗評價大鼠抑郁狀態(tài)和學(xué)習(xí)記憶功能,Western-blot及RT-PCR檢測大鼠海馬Glu R1和Glu R2及其m RNA表達(dá)。結(jié)果 ECT處理后,B、C、D組糖水偏好百分比變化均較A組和對照組明顯,其中D組升高最為明顯(均P0.05);B組逃避潛伏期延長且變化值與其他組均具有統(tǒng)計學(xué)差異,而D組逃避潛伏期縮短最為明顯,其次為A組(均P0.05);B組空間探索時間縮短且變化值均大于其他組,D組空間探索時間延長最為明顯(均P0.05)。ECT處理后,B、C、D組Glu R1表達(dá)較A組高,其中D組最高(均P0.05);Glu R1m RNA表達(dá)在組間無統(tǒng)計學(xué)差異B、C組Glu R2及其m RNA表達(dá)較其余組低,其中B組最低(均P0.05),A、D組和對照組間Glu R2及其m RNA差異無統(tǒng)計學(xué)意義(P0.05)。結(jié)論小劑量氯胺酮復(fù)合異丙酚麻醉在協(xié)同ECT抗抑郁效果的同時,能夠更大程度地改善ECT后學(xué)習(xí)記憶功能,其機(jī)制可能與上調(diào)海馬Glu R1和Glu R2表達(dá)相關(guān)。
[Abstract]:Objective to evaluate the effects of low-dose ketamine combined with propofol anesthesia on glutamate receptor subunit 1 (glutamate receptor subunit 1 Glu R1 and subunit 2 (glutamate receptor subunit 2Glu R2 in hippocampus of depressed rats after electroshock (electroconvulsive therapy,ECT). Methods Thirty-two healthy male SD rats were randomly divided into depression group (group A,), ECT group), and chronic mild unpredictable stress (chronic unpredictable mild stress,CUMS). ECT propofol group (group C) and ECT propofol ketamine group (group D) with 8 rats in each group. Another 8 normal rats were taken as control group. Group A was treated with pseudo-ECT after intraperitoneal injection of normal saline for 8 m L/kg. In group B, normal saline 8 mL / kg was injected intraperitoneally, propofol 80 mg/kg, propofol 80 mg/kg ketamine was treated with ECT for 10 mg/kg, and the above treatment lasted 7 days. The depression state and learning and memory function of rats were evaluated by sugar water preference test and Morris water maze test respectively. The expressions of Glu R1, Glu R2 and m RNA in hippocampus of rats were detected by Western-blot and RT-PCR. Results after ECT treatment, the percentage change of sugar water preference in group D was significantly higher than that in group A and control group, especially in group D (P0.05). The escape latency of group B was prolonged and the change value was significantly different from that of other groups, while the escape latency of group D was shortened most obviously, followed by group A (P0.05). The time of space exploration in group B was shorter than that in other groups, and the time of space exploration in group D was the most obvious (P0.05). After treatment with). ECT, the expression of Glu R1 in group D was higher than that in group A, among which the expression of Glu R1 in group D was the highest (P0.05). There was no significant difference in the expression of Glu R1m RNA between the two groups. The expression of Glu R2 and m RNA in group B was lower than that in group B (P0.05), but there was no significant difference in Glu R2 and m RNA between group A and control (P0.05). Conclusion low dose ketamine combined with propofol anesthesia can significantly improve the learning and memory function after ECT in combination with the antidepressant effect of ECT. The mechanism may be related to the up-regulation of the expression of Glu R1 and Glu R2 in hippocampus.
【作者單位】: 重慶醫(yī)科大學(xué)附屬第一醫(yī)院麻醉科;
【基金】:國家自然科學(xué)基金面上項目(編號:81271501) 國家臨床重點?平ㄔO(shè)項目經(jīng)費資助(編號:財社(2011)170號) 重慶市科委應(yīng)用開發(fā)項目經(jīng)費資助(編號:cstc2014yykf A110028)
【分類號】:R614

【共引文獻(xiàn)】

相關(guān)期刊論文 前10條

1 李額;田紹文;;抗抑郁效應(yīng)的mTOR信號級聯(lián)機(jī)制[J];華夏醫(yī)學(xué);2014年04期

2 Xiao-Lei AN;Fa-Dao TAI;;AVP and Glu systems interact to regulate levels of anxiety in BALB/cJ mice[J];動物學(xué)研究;2014年04期

3 張喜梅;陳景旭;;非單胺靶標(biāo)抗抑郁藥的研究進(jìn)展[J];國際精神病學(xué)雜志;2014年03期

4 王輝;張志s,

本文編號:2407704


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