内向整流机械门控双孔钾离子通道拮抗剂对抑郁症大鼠行为及齿状回神经再生的影响  

Effects of TREK-1 channel antagonist on behavior and dentate gyrus neurogenesis in depressed rats

作　　者：徐华 张俊华 张志珺[2] Xu Hua;Zhang Junhua;Zhang Zhijun(Department of Neurology,Jintan Hospital Affiliate to Jiangsu University,Changzhou 213200,Jiangsu Province,China)

机构地区：[1]江苏大学附属金坛医院神经内科,213200常州 [2]东南大学附属中大医院神经内科

出　　处：《中华老年心脑血管病杂志》2022年第12期1310-1314,共5页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：国家自然科学基金(31371074);金坛区科技项目(KJ201924)。

摘　　要：目的探讨内向整流机械门控双孔钾离子通道(TREK-1)拮抗剂对抑郁症大鼠行为及海马齿状回神经再生的影响。方法用慢性不可预见的温和性应激结合孤养法造模,筛选抑郁症大鼠18只,随机分为抑郁+生理盐水组、抑郁+氟西汀组及抑郁+SID1900组,每组6只;筛选同质性较高的正常饲养大鼠18只,随机分为正常+生理盐水组、正常+氟西汀组和正常+SID1900组,每组6只,分别腹腔注射氟西汀,SID1900以及等体积生理盐水。用免疫组织化学方法检测各组大鼠海马齿状回的新生细胞及新生细胞的分化和凋亡。结果抑郁+生理盐水组糖水偏好、开放场实验水平路程、垂直站立次数、体质量明显低于正常+生理盐水组,强迫游泳累计不动时间明显增加(P<0.01)。与正常+生理盐水组比较,正常+氟西汀组和正常+SID1900组5'-溴-2'-脱氧尿苷(BrdU)阳性细胞数明显增加(P<0.05),抑郁+生理盐水组BrdU阳性细胞数、神经元特异性核蛋白(NeuN)/BrdU双重标记阳性细胞数明显降低,TUNEL/BrdU双重标记阳性细胞数明显增加(P<0.01)。抑郁+氟西汀组和抑郁+SID1900组BrdU阳性细胞数、NeuN/BrdU双重标记阳性细胞数明显高于抑郁+生理盐水组,TUNEL/BrdU双重标记阳性细胞数明显低于抑郁+生理盐水组(P<0.05,P<0.01)。与抑郁+氟西汀组比较,抑郁+SID1900组大鼠强迫游泳累计不动时间明显减少[(52.29±17.43)s vs(98.26±18.90)s],体质量[(509.28±20.54)g vs(461.03±17.29)g]、NeuN/BrdU双重标记阳性细胞数[(510.83±67.29)个vs(369.20±54.01)个]明显增加(P<0.05)。结论TREK-1拮抗剂可能通过改善受损的海马神经再生及细胞存活来缓解大鼠的抑郁样症状。Objective To investigate the effect of the antagonist of tandem P-domain weak inward rectifying TREK-1 on the behavior and neurogenesis of hippocampal dentate gyrus in rats with depression.Methods After a rat model of depression was established with unpredictable chronic mild stress in combination with isolated living conditions,18 rats with depression were selected and randomly divided into depression+saline group,depression+fluoxetine group and depression+SID1900 group,with 6 rats in each group.Meanwhile,18 naive rats with high homogeneity were randomly divided into normal+saline group,normal+fluoxetine group and normal+SID1900 group,6 rats per group.Fluoxetine,SID1900 and equal volume of saline were injected intraperito-neally to the corresponding rats.The immunohistochemical assay was used to detect newborn cells in the dentate gyrus as well as differentiation and apoptosis of the cells.Results The depres-sion+saline group had dramatically lower ratio of sucrose consumption,shorter total movement distance in open field test,less rearing times and lower body weight,but significantly longer im-mobility time in forced swimming test in the depression+saline group than the normal+saline group(P<0.01).When compared with the normal+saline group,the number of BrdU positive cells was significantly increased in the normal+fluoxetine group and the normal+SID1900 group(P<0.05).However,the numbers of BrdU positive and NeuN/BrdU double positive cells were decreased dramatically,but the number of TUNEL/BrdU positive cells was markedly higher in the depression+saline group than the normal+saline group(P<0.01).The numbers of BrdU positive cells and the NeuN/BrdU double positive cells were obviously larger,but that of TUNEL/BrdU positive cells were reduced markedly in the depression+fluoxetine group and the depression+SID1900 group than the depression+saline group(P<0.05,P<0.01).Notably,SID1900 treatment resulted in shorter immobility time(52.29±17.43 s vs 98.26±18.90 s,P<0.05),larger body weight(509.28±20.54 g vs 461.03±1

关 键 词：抑郁症 海马 氟西汀 齿状回 细胞增殖 

分 类 号：R749.4[医药卫生—神经病学与精神病学]