中华行为医学与脑科学杂志
中華行為醫學與腦科學雜誌
중화행위의학여뇌과학잡지
CHINESE JOURNAL OF BEHAVIORAL MEDICINE AND BRAIN SCIENCE
2015年
5期
385-388
,共4页
陈冠婕%吴迪%彭正午%王莹%谭庆荣
陳冠婕%吳迪%彭正午%王瑩%譚慶榮
진관첩%오적%팽정오%왕형%담경영
抑郁症%治疗抵抗%白介素-1β%氟西汀
抑鬱癥%治療牴抗%白介素-1β%氟西汀
억욱증%치료저항%백개소-1β%불서정
Depression%Treatment-resistant%Interleukin-1β%Fluoxetine
目的 利用对氟西汀不敏感小鼠的抑郁行为模拟难治性抑郁临床表现,并分析其行为和脑内白介素-1β(IL-1β)表达水平之间关系.方法 50只BALB/c小鼠随机分为对照组(Control),模型组(chronic unpredictable mild stress,CUMS)及模型+治疗组,分别接受常规饲养9周,CUMS处理9周及CUMS处理8周+氟西汀处理1周.在第9周结束时,根据氟西汀抗抑郁治疗效果,从模型+治疗组中筛选出氟西汀疗效不佳小鼠,即治疗抵抗小鼠(antidepressant treatment-resistant mice,ATRM),以及症状改善小鼠,即一般抑郁小鼠(depression mice,DM).对Control组、CUMS组、ATRM组以及DM组进行体质量检测、旷场和强迫游泳测试,随后处死动物、提取脑组织进行IL-1β的Elisa检测,比较组间差异.结果 (1)体质量测试:1周盐酸氟西汀抗抑郁治疗未能改善ATRM组小鼠体质量偏低现象.ATRM体质量[(18.56±7.56)g]与CUMS组[(19.03±8.58)g]比较差异无统计学意义,与Control组、DM组小鼠体质量[分别为(24.56±5.45)g,(20.12±9.17)g]比较,差异有统计学意义(P＜0.05).(2)旷场和强迫游泳实验:旷场实验中,水平运动距离(F=0.355)及进入中心区次数(F=0.327)的组间比较差异无统计学意义;强迫游泳实验中,ATRM游泳不动时间[(241.50±36.55)s]较DM组[(156.00±25.47)s]明显延长(F=13.573,P＜0.05).(3)脑内IL-1β的Elisa检测结果:ATRM脑内IL-1β水平[(164.90±46.70) pg/mg]显著高于Control组和DM组小鼠[分别为:(72.94±1.44) pg/mg,(93.09±4.65) pg/mg](P＜0.01),与CUMS组小鼠相比差异无统计学意义.ATR小鼠的抑郁样行为表现与其脑内IL-1β水平呈正相关(r=0.669,P=0.006).结论 CUMS可在BALB/c小鼠身上较好地模拟出难治性抑郁针对治疗抵抗的疾病特点,中枢内IL-1β水平的升高可能在难治性抑郁形成中具有重要作用.
目的 利用對氟西汀不敏感小鼠的抑鬱行為模擬難治性抑鬱臨床錶現,併分析其行為和腦內白介素-1β(IL-1β)錶達水平之間關繫.方法 50隻BALB/c小鼠隨機分為對照組(Control),模型組(chronic unpredictable mild stress,CUMS)及模型+治療組,分彆接受常規飼養9週,CUMS處理9週及CUMS處理8週+氟西汀處理1週.在第9週結束時,根據氟西汀抗抑鬱治療效果,從模型+治療組中篩選齣氟西汀療效不佳小鼠,即治療牴抗小鼠(antidepressant treatment-resistant mice,ATRM),以及癥狀改善小鼠,即一般抑鬱小鼠(depression mice,DM).對Control組、CUMS組、ATRM組以及DM組進行體質量檢測、曠場和彊迫遊泳測試,隨後處死動物、提取腦組織進行IL-1β的Elisa檢測,比較組間差異.結果 (1)體質量測試:1週鹽痠氟西汀抗抑鬱治療未能改善ATRM組小鼠體質量偏低現象.ATRM體質量[(18.56±7.56)g]與CUMS組[(19.03±8.58)g]比較差異無統計學意義,與Control組、DM組小鼠體質量[分彆為(24.56±5.45)g,(20.12±9.17)g]比較,差異有統計學意義(P＜0.05).(2)曠場和彊迫遊泳實驗:曠場實驗中,水平運動距離(F=0.355)及進入中心區次數(F=0.327)的組間比較差異無統計學意義;彊迫遊泳實驗中,ATRM遊泳不動時間[(241.50±36.55)s]較DM組[(156.00±25.47)s]明顯延長(F=13.573,P＜0.05).(3)腦內IL-1β的Elisa檢測結果:ATRM腦內IL-1β水平[(164.90±46.70) pg/mg]顯著高于Control組和DM組小鼠[分彆為:(72.94±1.44) pg/mg,(93.09±4.65) pg/mg](P＜0.01),與CUMS組小鼠相比差異無統計學意義.ATR小鼠的抑鬱樣行為錶現與其腦內IL-1β水平呈正相關(r=0.669,P=0.006).結論 CUMS可在BALB/c小鼠身上較好地模擬齣難治性抑鬱針對治療牴抗的疾病特點,中樞內IL-1β水平的升高可能在難治性抑鬱形成中具有重要作用.
목적 이용대불서정불민감소서적억욱행위모의난치성억욱림상표현,병분석기행위화뇌내백개소-1β(IL-1β)표체수평지간관계.방법 50지BALB/c소서수궤분위대조조(Control),모형조(chronic unpredictable mild stress,CUMS)급모형+치료조,분별접수상규사양9주,CUMS처리9주급CUMS처리8주+불서정처리1주.재제9주결속시,근거불서정항억욱치료효과,종모형+치료조중사선출불서정료효불가소서,즉치료저항소서(antidepressant treatment-resistant mice,ATRM),이급증상개선소서,즉일반억욱소서(depression mice,DM).대Control조、CUMS조、ATRM조이급DM조진행체질량검측、광장화강박유영측시,수후처사동물、제취뇌조직진행IL-1β적Elisa검측,비교조간차이.결과 (1)체질량측시:1주염산불서정항억욱치료미능개선ATRM조소서체질량편저현상.ATRM체질량[(18.56±7.56)g]여CUMS조[(19.03±8.58)g]비교차이무통계학의의,여Control조、DM조소서체질량[분별위(24.56±5.45)g,(20.12±9.17)g]비교,차이유통계학의의(P＜0.05).(2)광장화강박유영실험:광장실험중,수평운동거리(F=0.355)급진입중심구차수(F=0.327)적조간비교차이무통계학의의;강박유영실험중,ATRM유영불동시간[(241.50±36.55)s]교DM조[(156.00±25.47)s]명현연장(F=13.573,P＜0.05).(3)뇌내IL-1β적Elisa검측결과:ATRM뇌내IL-1β수평[(164.90±46.70) pg/mg]현저고우Control조화DM조소서[분별위:(72.94±1.44) pg/mg,(93.09±4.65) pg/mg](P＜0.01),여CUMS조소서상비차이무통계학의의.ATR소서적억욱양행위표현여기뇌내IL-1β수평정정상관(r=0.669,P=0.006).결론 CUMS가재BALB/c소서신상교호지모의출난치성억욱침대치료저항적질병특점,중추내IL-1β수평적승고가능재난치성억욱형성중구유중요작용.
Objective To investigate the correlationship between depressed behaviors and interleukin-1β (IL-1β) in brain tissue in mice which are insensitive to fluoxetine,and to mimic the treatment resistant depression (TRD) in clinical condition.Methods 50 BALB/c mice were randomly divided into Control group (Control),Chronic unpredictable mild stress (CUMS) group and CUMS+fluoxetine group.Mice in Control group were raised ad libitum for 9 weeks,those in CUMS group received CUMS for 9 weeks and those in CUMS+fluoxetine group received 8 weeks' CUMS followed 1 week' s treatment with Fluoxetine(10 mg · kg-1 · d-1).At the end of the 9th week,mice in(CUMS + treatment)group were selected into antidepressant treatment-resistant mice(ATRM) as no remission and Depression Group (DM) as symptoms improved.Body mass test (BMT),open field test (OFT) and forces swim test (FST) were completed respectively in these 4 groups at the endpoint of the experiment,and the brain tissue were extracted after the tests for IL-1β Elisa test.Results (1) BMT:there was no effect of weightgain in ATRM after 1 week' s therapy with Fluoxetine.There was no difference in body-weight between ATRM ((18.56±7.56) g) and CUMS ((19.03± 8.58) g) mice,while compared with Control ((24.56±5.45) g) and DM mice ((20.12±9.17) g) ATRM and CUMS mile's body weight were significantly lower (P＜0.05).(2)OFT and FST:in OFT,there was no significant difference in of horizontal moving distance(F=0.355) either in the frequencies of entering the central zone (F=0.327) among the 4 groups;in OFT,the immobility time of ATRM ((241.50 ± ± 36.55) s) was significantly longer than that in DM ((156.00± 25.47) s) (F=13.573,P＜0.05).(3) Elisa test of IL-1β:the brain' s IL-1β serum level in ATRM ((164.90±46.70) pg/mg) was higher than those in Control ((69.68±6.56) pg/mg)),and DM ((93.09±4.65) pg/mg) (P＜0.01),while no difference with that in CUMS mice.Additionally,the depressive behaviors in ATRM showed its positive correlation with the IL-1β level in CNS (r=0.669,P=0.006).Conclusion CUMS can elicit the refractory depressive symptoms in BALB/c mice to simulate TRD' s characteristic,and the elevated level of IL-1 β within brain tissue may play an important role in the development of TRD.
