下丘脑NK2受体在应激介导抑郁症发生中的作用

目的 阐明神经激肽A的受体NK2在慢性不可预见性温和刺激(CUMS)所致的抑郁样行为发生、发展中的可能作用和机制.方法 SD大鼠随机分为对照组、氟西汀组和抑郁模型组3组,行为学检测后,氟西汀组和抑郁模型组均给予孤养+CUMS造成大鼠抑郁症模型,再次行为学检测后,氟西汀组大鼠给予氟西汀腹腔注射21d,抑郁模型组给予同体积生理盐水腹腔注射21d,再次进行行为学检测,麻醉后取大鼠下丘脑,提取组织mRNA和蛋白后,采用荧光定量PCR技术和Western Blot技术检测NK2的表达.结果 应激前3组大鼠的糖水偏好率和强迫游泳的不动时间均无统计学意义.应激后,氟西汀组和抑郁模型组大鼠的糖水摄入明显减少、强迫游泳不动时间明显增长,差异均有统计学意义(P＜0.05).而给予氟西汀后,氟西汀组大鼠的糖水偏好率有所增加,强迫游泳的不动时间有所减少,与对照组比较差异无统计学意义(P＞0.05),但与抑郁组大鼠相比,差异均有统计学意义(P＜0.05).与对照组和氟西汀组比较,抑郁组下丘脑NK2受体的mRNA和蛋白的表达量明显升高,差异有统计学意义(P＜0.05),而氟西汀组与对照组相比差异无统计学意义(P＞0.05).结论 CUMS可引起大鼠行为学改变,造成大鼠抑郁模型;NK2受体的mRNA和蛋白的表达量在应激后大鼠的下丘脑中明显升高,经氟西汀干预后可恢复到正常水平,说明NK2受体与抑郁症的发生、发展过程具有相关性,在抑郁症的发病机制中可能发挥重要作用.

Effect of hypothalamic neurokinin-2 receptor on depression induced by stress

Objective To investigate the effect and mechanism of neurokinin-2 (NK2) receptor on depression behaviors induced by chronic unpredictable mild stimulations (CUMS).Methods SD rats were randomly divided into control group,CUMS group and CUMS+fluoxetine group.Experimental depression model was set up under three-week period of social isolation rearing and CUMS.Rats in CUMS group and CUMS+fluoxetine group were treated with normal saline and fluoxetine for 3 weeks,respectively.The sucrose preference test and forced swimming test (FST) were used to explore the effects of stress and fluoxetine on anhedonia and activity.The expression level of NK2 in hypothalamus were determined by real-time fluorescence quantitative PCR and Western blot.Results No significant differences were found between three groups in sucrose preference and immobility time of FST before stress (P ＞ 0.05).Compared with control group,rats in CUMS group and CUMS+ fluoxetine group exhibited decrease sucrose preference (P ＜ 0.05) and increase immobility time of FST (P ＜ 0.05).However,after given fluoxetine for 21 d,CUMS+ fluoxetine group showed no significant difference compared with control group in sucrose preference and the immobility time of FST (P ＞ 0.05).Compared with control rats,the mRNA and protein expression of NK2 in hippocampus increased significantly in CUMS group (P ＜ 0.05).After fluoxetine treatment,the mRNA and protein expression of NK2 in hypothalamus showed no significant difference with control group (P ＞ 0.05).Conclusions SD rats depression model established by CUMS and separation is feasible and effective.Stress rats showes marked increase in mRNA and protein expression of NK2 in hypothalamus,and treatment with fluoxetine could reverse these changes.NK2 possesses an important role in depression and may be a new therapeutic target for depression.