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
2013年
4期
289-292
,共4页
陈怡环%王磊%杨帆%吴迪%彭正午%王化宁%谭庆荣
陳怡環%王磊%楊帆%吳迪%彭正午%王化寧%譚慶榮
진이배%왕뢰%양범%오적%팽정오%왕화저%담경영
喹硫平%慢性不可预见应激%磷酸化细胞外信号调节激酶%大鼠%海马
喹硫平%慢性不可預見應激%燐痠化細胞外信號調節激酶%大鼠%海馬
규류평%만성불가예견응격%린산화세포외신호조절격매%대서%해마
Qutiapine%Chronic unpredictable stress%Phosphorylated extracellular signal-regulated protein kinase%Rat%Hippocampus
目的 观察喹硫平(quetiapine,QUE)对慢性不可预见应激(chronic unpredictable stress,CUS)模型大鼠行为学的改善作用及对海马磷酸化细胞外信号调节激酶(phosphorylated extracellular signal-regulated protein kinase,pERK1/2)表达的影响.方法 32只SD大鼠按随机数字表法分为对照组(Control)、模型组(CUS)、CUS+ QUE(5 mg/kg,L)组及CUS+ QUE(10 mg/kg,M)组,每组8只.除Control组外,余各组大鼠均接受CUS造模28 d,随后Control组和CUS组大鼠连续7d接受含1％二甲基亚砜的生理盐水(5 ml/kg体质量)腹腔注射,CUS+QUE(L)组和CUS+ QUE(M)组大鼠腹腔注射QUE(分别为5 mg/kg和10 mg/kg体质量),连续7d.实验期间观察大鼠体质量的变化并在给药结束后采用旷场实验和强迫游泳实验评估大鼠抑郁样行为,用蛋白质印迹法(Western blot)检测大鼠海马pERK1/2的表达水平.结果 (1)体质量测试:持续28 d的慢性不可预见应激抑制了动物体质量的增长(F=7.969,P＜0.05),而给予10 mg/kg的喹硫平可以改善这种现象(与CUS组比较,P＜ 0.05),给予5 mg/kg的喹硫平差异无统计学意义(P＞0.05).(2)旷场和强迫游泳实验:各处理组大鼠在水平活动距离(F=17.846),进入中央区的总次数(F=4.720)以及强迫游泳静止时间(F=26.090),均差异有统计学意义(均P＜0.05).与CUS组大鼠比较,Control组和CUS+ QUE (M)组大鼠水平活动距离和进入中央区的总次数均显著增加,静止时间明显减少[分别为:CUS组:(6696.30±1061.19)mm,(19.63 ±9.15)次,(110.73±15.98)s；Control组:(10824.61±1399.37) mm,(37.75±13.02)次,(66.13 ±5.18) s;CUS+ QUE(M)组:9637.51±1630.16) mm,(32.38±6.23)次,(73.40±11.99)s;均P＜0.05].而CUS+ QUE(L)组与CUS组相比上述指标差异无统计学意义(均P＞0.05).(3)Western blot结果显示,CUS组大鼠海马pERK1/2的表达水平低于Control组和CUS+QUE(M)组,而与CUS+ QUE(L)组之间差异无统计学意义(F=6.641,P＜0.01).结论 喹硫平能够改善CUS动物的抑郁行为,而这一作用可能与其促进海马pERK1/2的表达有关.
目的 觀察喹硫平(quetiapine,QUE)對慢性不可預見應激(chronic unpredictable stress,CUS)模型大鼠行為學的改善作用及對海馬燐痠化細胞外信號調節激酶(phosphorylated extracellular signal-regulated protein kinase,pERK1/2)錶達的影響.方法 32隻SD大鼠按隨機數字錶法分為對照組(Control)、模型組(CUS)、CUS+ QUE(5 mg/kg,L)組及CUS+ QUE(10 mg/kg,M)組,每組8隻.除Control組外,餘各組大鼠均接受CUS造模28 d,隨後Control組和CUS組大鼠連續7d接受含1％二甲基亞砜的生理鹽水(5 ml/kg體質量)腹腔註射,CUS+QUE(L)組和CUS+ QUE(M)組大鼠腹腔註射QUE(分彆為5 mg/kg和10 mg/kg體質量),連續7d.實驗期間觀察大鼠體質量的變化併在給藥結束後採用曠場實驗和彊迫遊泳實驗評估大鼠抑鬱樣行為,用蛋白質印跡法(Western blot)檢測大鼠海馬pERK1/2的錶達水平.結果 (1)體質量測試:持續28 d的慢性不可預見應激抑製瞭動物體質量的增長(F=7.969,P＜0.05),而給予10 mg/kg的喹硫平可以改善這種現象(與CUS組比較,P＜ 0.05),給予5 mg/kg的喹硫平差異無統計學意義(P＞0.05).(2)曠場和彊迫遊泳實驗:各處理組大鼠在水平活動距離(F=17.846),進入中央區的總次數(F=4.720)以及彊迫遊泳靜止時間(F=26.090),均差異有統計學意義(均P＜0.05).與CUS組大鼠比較,Control組和CUS+ QUE (M)組大鼠水平活動距離和進入中央區的總次數均顯著增加,靜止時間明顯減少[分彆為:CUS組:(6696.30±1061.19)mm,(19.63 ±9.15)次,(110.73±15.98)s；Control組:(10824.61±1399.37) mm,(37.75±13.02)次,(66.13 ±5.18) s;CUS+ QUE(M)組:9637.51±1630.16) mm,(32.38±6.23)次,(73.40±11.99)s;均P＜0.05].而CUS+ QUE(L)組與CUS組相比上述指標差異無統計學意義(均P＞0.05).(3)Western blot結果顯示,CUS組大鼠海馬pERK1/2的錶達水平低于Control組和CUS+QUE(M)組,而與CUS+ QUE(L)組之間差異無統計學意義(F=6.641,P＜0.01).結論 喹硫平能夠改善CUS動物的抑鬱行為,而這一作用可能與其促進海馬pERK1/2的錶達有關.
목적 관찰규류평(quetiapine,QUE)대만성불가예견응격(chronic unpredictable stress,CUS)모형대서행위학적개선작용급대해마린산화세포외신호조절격매(phosphorylated extracellular signal-regulated protein kinase,pERK1/2)표체적영향.방법 32지SD대서안수궤수자표법분위대조조(Control)、모형조(CUS)、CUS+ QUE(5 mg/kg,L)조급CUS+ QUE(10 mg/kg,M)조,매조8지.제Control조외,여각조대서균접수CUS조모28 d,수후Control조화CUS조대서련속7d접수함1％이갑기아풍적생리염수(5 ml/kg체질량)복강주사,CUS+QUE(L)조화CUS+ QUE(M)조대서복강주사QUE(분별위5 mg/kg화10 mg/kg체질량),련속7d.실험기간관찰대서체질량적변화병재급약결속후채용광장실험화강박유영실험평고대서억욱양행위,용단백질인적법(Western blot)검측대서해마pERK1/2적표체수평.결과 (1)체질량측시:지속28 d적만성불가예견응격억제료동물체질량적증장(F=7.969,P＜0.05),이급여10 mg/kg적규류평가이개선저충현상(여CUS조비교,P＜ 0.05),급여5 mg/kg적규류평차이무통계학의의(P＞0.05).(2)광장화강박유영실험:각처리조대서재수평활동거리(F=17.846),진입중앙구적총차수(F=4.720)이급강박유영정지시간(F=26.090),균차이유통계학의의(균P＜0.05).여CUS조대서비교,Control조화CUS+ QUE (M)조대서수평활동거리화진입중앙구적총차수균현저증가,정지시간명현감소[분별위:CUS조:(6696.30±1061.19)mm,(19.63 ±9.15)차,(110.73±15.98)s；Control조:(10824.61±1399.37) mm,(37.75±13.02)차,(66.13 ±5.18) s;CUS+ QUE(M)조:9637.51±1630.16) mm,(32.38±6.23)차,(73.40±11.99)s;균P＜0.05].이CUS+ QUE(L)조여CUS조상비상술지표차이무통계학의의(균P＞0.05).(3)Western blot결과현시,CUS조대서해마pERK1/2적표체수평저우Control조화CUS+QUE(M)조,이여CUS+ QUE(L)조지간차이무통계학의의(F=6.641,P＜0.01).결론 규류평능구개선CUS동물적억욱행위,이저일작용가능여기촉진해마pERK1/2적표체유관.
Objective To investigate the effect of quetiapine on the behavior and expression of pERK1/2 in chronic unpredictable stress(CUS) model rats.Methods 32 adult male Sprague Dawley rats were randomly divided into four groups (n =8 for each group):control group,CUS group,CUS + QUE (5 mg/kg,L) group and CUS + QUE(10 mg/kg,M)group.The rats in control group were left undisturbed in their home cage for 28 days and the other groups were exposed to 28 consecutive days of CUS,then the rats in control group and CUS group were treated with 1％ DMSO in saline (5 ml/kg,intraperitoneal injection),the rats in CUS + QUE (L)group and CUS + QUE(M) group respectively treated with quetiapine (5 mg/kg)or quetiapine(10 mg/kg) for consecutive 7 days.The weight data of each group were recorded,and the behavioral changes in these rats were analyzed by open field test and forced swimming test;and the expression of pERK1/2 was measured by Western blot.Results (1)Compared with control group,quetiapine (10 mg/kg) ameliorated the inhibition of body weight gain that induced by chronic unpredictable stress (P ＜ 0.05),but quetiapine (5 mg/kg) did not have this effect.(2)Open field and Forced swimming test showed significant difference (P ＜ 0.05) of horizontal motion distance (F =17.846),the number of central region entering(F=4.720) and the immobility time(F=26.090) in each group.And these tests showed that horizontal motion distance and the number of central region entering in CUS group ((6696.30 ±1061.19)mm,(19.63 ±9.15)times) were significantly lower than that of control group ((10824.61 ± 1399.37) mm,(37.75 ± 13.02) times) and CUS + QUE (M) group ((9637.51 ± 1630.16) mm,(32.38 ± 6.23)),while the immobility time (110.73 ± 15.98)s were significantly higher than that of control group((66.13 ± 5.18)s)and CUS + QUE (M) group((73.40 ± 11.99) s,P ＜ 0.05).But there was no significant difference between that of CUS group and CUS + QUE(L) group(P＞0.05).(3)The expression of pERK1/2 in CUS group showed significant decrease when compared with control group or CUS + QUE (M) group,but showed no significant difference with CUS + QUE(L) group(F=6.641,P＜ 0.01).Conclusion Quetiapine can ameliorate depressive-like behaviors induced by chronic unpredictable stress,and this effect may be carried out by up-regulation the expression of pERK1/2 in the hippocampus.
