目的探讨TREK-1钾通道拮抗剂对抑郁模型大鼠行为学改善的影响。方法48只健康成年雄性SD大鼠分为正常+生理盐水组(CON)、正常+Fluoxetine组(CON+FLU)、正常+SIDl900组(CON+SID)、抑郁模型+生理盐水组(CUMS)、抑郁模型+Fluoxetine组(CUMS+FLU),抑郁模型+SIDl900组(CUMS+SID),每组8只。采用孤养结合慢性不可预见的温和性应激(Chronic unpredicted mild stress, CUMS)方法建立抑郁大鼠模型,建模4周后分别腹腔注射氟西汀10mg·kg^-1、SIDl9005.1mg·kg^-1以及等体积生理盐水,抑郁模型组持续给予应激刺激至实验结束。药物处理7d、14d、21d和28d后观察各组大鼠的体质量及行为学(包括蔗糖水偏好实验、旷场实验和强迫游泳实验)变化。结果药物干预对正常大鼠的体质量及行为学表现无明显影响(P〉0.05),应激刺激显著降低大鼠的体质量、蔗糖水消耗百分比以及在旷场实验中的运动距离及站立次数,增加强迫游泳实验中的不动时间(均P〈0.01);药物干预14d,CUMS+SID组蔗糖水消耗百分比及旷场实验中站立次数[分别为(62.03±6.99)%,(18.57±6.37)次]高于CUMS组[分别为(45.46±15.54)%,(5.83±3.06)次],强迫游泳不动时间[(123.57±26.73)S]低于CUMS组[(174.33±40.68)s],差异有统计学意义(P〈0.05);28d后,CUMS+FLU组蔗糖水消耗百分比及旷场实验中运动路程、站立次数[分别为(79.64±11.37)%,(13.18±3.17)m,(19.33+3.33)次]高于CUMS组[分别为(48.06±17.10)%,(4.45±3.69)m,(5.17±2.99)次],不动时间[(97.83±18.97)s]低于CUMS[(194.83±37.97)s],差异有统计学意义(P〈0.05),CUMS+SID组不动时间[(44.29±14.30)S]低于CUMS+FLU组[(97.83±18.97)s],差异有统计学意义(P〈0.01)。结论拮抗TREK-1钾通?
Objective To study the effect of TREK-1 potassium channel blocker on the behavior in rats with depression. Methods Forty-eight healthy adult male Sprague Dawley (SD) rats were divided into 6 groups as following : control + saline ( CON group), control + fluoxetine ( CON + FLU group ), control + SID1900 (CON+SID group) ,CUMS + saline (CUMS group) ,CUMS + fluoxetine (CUMS+FLU group) and CUMS + SID1900 (CUMS+SID group) with 8 in each group. Isolated living conditions combining chronic unpredicted mild stress (CUMS) were used to establish depression model in rats. Four weeks after modeling, fluoxetine 10 mg · kg^-1 ,SID1900 5.1 mg · kg^-1 and 0.9% sodium chloride were given by intraperitoneal injection respectively. Body weight and behavioral performance of rats in several experiment paradigms were measured after drug administration. The behavioral paradigms included sucrose preference test(SPT) ,open field test(OFT) and forced swimming test(FST). Results Drug administration had no significant effect on body weight and behavioral performance in non stress rats (P〉0.05), however, after chronic unpredicted mild stress the body weight, percentage of sucrose consumption, movement distances and rearing times in CUMS group were decreased dramatically contrast to CON group, but the immobility duration was increased significantly (all P〈0.001 ). After treatment with drug for 14 days, the sucrose consumption percentage (62.03 ± 6.99) %) and rearing times ( 18.57 ± 6.37) in CUMS + SID group were increased contrast to CUMS group ((45.46±15.54) %, (5.83±3.06)) ,while the immobility time( (123.57±26.73) s) was decreased compared with that in CUMS group((174.33±40.68) s). When drug administration for 28 days ,the sucrose consumption percentage( (79.64±11.37)%),the total distance as well as the rearing times ((13.18±3.17) m, (19.33±3.33) ) within OFT in CUMS+FLU group were increased