中华精神科杂志
中華精神科雜誌
중화정신과잡지
CHINESE JOURNA OF PSYCHIATRY
2011年
3期
163-168
,共6页
隋毓秀%张志珺%郭怡菁%孙奕
隋毓秀%張誌珺%郭怡菁%孫奕
수육수%장지군%곽이정%손혁
氟西汀%抑郁%信号传导%神经再生%慢性不可预知温和应激模型
氟西汀%抑鬱%信號傳導%神經再生%慢性不可預知溫和應激模型
불서정%억욱%신호전도%신경재생%만성불가예지온화응격모형
Fluoxetine%Depression%Signal transduction%Nerve regeneration%Chronic unpredictable mild stress
目的 探讨Notch1信号系统在抑郁海马神经再生障碍中的作用.方法 选择行为学评分相近的68只Sprague-Dawley大鼠,分为对照组、对照+氟西汀组、慢性不可预知温和应激(CUMS)组,CUMS+氟西汀组,每组17只.应用CUMS建立抑郁模型后进行行为学评估;采用免疫组织化学方法检测大鼠海马神经干细胞的增殖和存活;采用实时定量聚合酶链反应和蛋白免疫印迹方法测定Notchl信号通路各个因子(NICD、Hes1、Hes5、Jag1)的基因及蛋白表达水平的改变.结果 (1)干预前,各组体质量、糖水偏好、旷场试验、强迫游泳评分的差异均无统计学意义(P>0.05);干预后,与对照组比较,CUMS组糖水偏好、水平得分和垂直得分降低,漂浮不动时间增加,差异均有统计学意义(P<0.001);与CUMS组比较,CUMS+氟西汀组糖水偏好、水平得分和垂直得分增加,漂浮不动时间降低,差异均有统计学意义(P<0.01);(2)神经干细胞的增殖和存活:与CUMS组(1900.33±104.10)比较,CUMS+氟西汀组(3047.61±158.29)神经干细胞的增殖数显著上升,差异有统计学意义(P<0.01);与CUMS组(1845.33±126.88)比较,CUMS+氟西汀组(2704.21±154.31)神经干细胞的存活数显著上升,差异有统计学意义(P<0.01);(3)海马Notch1信号通路基因和蛋白的表达:CUMS+氟西汀组小鼠抗大鼠Notch1(NICD)mRNA、Hes1 mRNA、Hes5 mRNA、Jag1 mRNA基因表达与CUMS组比较显著上升,差异均有统计学意义(P<0.01);CUMS+氟西汀组NICD、Hes5、Jag1蛋白水平与CUMS组比较显著上升,差异均有统计学意义(P<0.01).结论 Notch1信号系统可能参与慢性应激模型大鼠海马神经再生障碍;氟西汀可能通过上调Notch1信号系统改善海马神经再生,从而缓解大鼠抑郁症状.
目的 探討Notch1信號繫統在抑鬱海馬神經再生障礙中的作用.方法 選擇行為學評分相近的68隻Sprague-Dawley大鼠,分為對照組、對照+氟西汀組、慢性不可預知溫和應激(CUMS)組,CUMS+氟西汀組,每組17隻.應用CUMS建立抑鬱模型後進行行為學評估;採用免疫組織化學方法檢測大鼠海馬神經榦細胞的增殖和存活;採用實時定量聚閤酶鏈反應和蛋白免疫印跡方法測定Notchl信號通路各箇因子(NICD、Hes1、Hes5、Jag1)的基因及蛋白錶達水平的改變.結果 (1)榦預前,各組體質量、糖水偏好、曠場試驗、彊迫遊泳評分的差異均無統計學意義(P>0.05);榦預後,與對照組比較,CUMS組糖水偏好、水平得分和垂直得分降低,漂浮不動時間增加,差異均有統計學意義(P<0.001);與CUMS組比較,CUMS+氟西汀組糖水偏好、水平得分和垂直得分增加,漂浮不動時間降低,差異均有統計學意義(P<0.01);(2)神經榦細胞的增殖和存活:與CUMS組(1900.33±104.10)比較,CUMS+氟西汀組(3047.61±158.29)神經榦細胞的增殖數顯著上升,差異有統計學意義(P<0.01);與CUMS組(1845.33±126.88)比較,CUMS+氟西汀組(2704.21±154.31)神經榦細胞的存活數顯著上升,差異有統計學意義(P<0.01);(3)海馬Notch1信號通路基因和蛋白的錶達:CUMS+氟西汀組小鼠抗大鼠Notch1(NICD)mRNA、Hes1 mRNA、Hes5 mRNA、Jag1 mRNA基因錶達與CUMS組比較顯著上升,差異均有統計學意義(P<0.01);CUMS+氟西汀組NICD、Hes5、Jag1蛋白水平與CUMS組比較顯著上升,差異均有統計學意義(P<0.01).結論 Notch1信號繫統可能參與慢性應激模型大鼠海馬神經再生障礙;氟西汀可能通過上調Notch1信號繫統改善海馬神經再生,從而緩解大鼠抑鬱癥狀.
목적 탐토Notch1신호계통재억욱해마신경재생장애중적작용.방법 선택행위학평분상근적68지Sprague-Dawley대서,분위대조조、대조+불서정조、만성불가예지온화응격(CUMS)조,CUMS+불서정조,매조17지.응용CUMS건립억욱모형후진행행위학평고;채용면역조직화학방법검측대서해마신경간세포적증식화존활;채용실시정량취합매련반응화단백면역인적방법측정Notchl신호통로각개인자(NICD、Hes1、Hes5、Jag1)적기인급단백표체수평적개변.결과 (1)간예전,각조체질량、당수편호、광장시험、강박유영평분적차이균무통계학의의(P>0.05);간예후,여대조조비교,CUMS조당수편호、수평득분화수직득분강저,표부불동시간증가,차이균유통계학의의(P<0.001);여CUMS조비교,CUMS+불서정조당수편호、수평득분화수직득분증가,표부불동시간강저,차이균유통계학의의(P<0.01);(2)신경간세포적증식화존활:여CUMS조(1900.33±104.10)비교,CUMS+불서정조(3047.61±158.29)신경간세포적증식수현저상승,차이유통계학의의(P<0.01);여CUMS조(1845.33±126.88)비교,CUMS+불서정조(2704.21±154.31)신경간세포적존활수현저상승,차이유통계학의의(P<0.01);(3)해마Notch1신호통로기인화단백적표체:CUMS+불서정조소서항대서Notch1(NICD)mRNA、Hes1 mRNA、Hes5 mRNA、Jag1 mRNA기인표체여CUMS조비교현저상승,차이균유통계학의의(P<0.01);CUMS+불서정조NICD、Hes5、Jag1단백수평여CUMS조비교현저상승,차이균유통계학의의(P<0.01).결론 Notch1신호계통가능삼여만성응격모형대서해마신경재생장애;불서정가능통과상조Notch1신호계통개선해마신경재생,종이완해대서억욱증상.
Objective To investigate whether the effect of fluoxetine on hippocampal neurogenesis involves Notch1 signaling after chronic stress. Methods Sixty-eight male Sprague-Dawley rats were divided into control group, control + fluoxetine group, depression model group and depression model + fluoxetine group. Chronic unpredictable mild stress (CUMS) was used to make up depression animal model. The function of Notch1 signaling was measured by real-time PCR and western blotting. Simultaneously,hippocampal neurogenesis was monitored by assessing cell proliferation and survival. Results (1) Before starting CUMS protocol, the animals exhibited equivalent weight, sucrose preference, number of squares crossed, number of rearing, and immobility time in behavioral test. Twenty-eight days after CUMS protocol,these parameters were significantly difference in rats exposed to CUMS compared with the controls (sucrose preference, number of squares crossed, number of grooming and rearing, and immobility time, P<0. 01).Administration of fluoxetine was shown to dramatically improve the depression behavior (P<0. 01) .(2) The cell proliferation [(3047. 61 ± 158. 29) vs. (1900. 33 ± 104. 10)] and survive [(2704. 21 ±154. 31) vs. (1845.33 ± 126.88)] were increased after fluoxetine administration in rats with depression (P<0. 01). (3) Fluoxetine increased mRNA expressions of Notch1 signaling components [NICD mRNA (0. 23 ±0. 01) vs. (0. 10 ±0.01), Hes1 mRNA (0. 56 ±0.04) vs. (0. 28 ±0.02), Hes5 mRNA (0. 24 ±0.02) vs. (0.10 ±0.02), Jag1 mRNA (0.82 ±0.06) vs. (0.56 ±0.03)] in the rat hippocampus compared with the CUMS group (P<0. 01 or P<0. 001). Fluoxetine enhanced protein levels of Notch1 signaling components [NICD(1.99 ±0.07) vs. (0.53 ±0.10), Hes5(0. 64 ±0. 04) vs. (0.37 ±0.09),Jag1 (2. 34 ± 0. 13) vs. (0. 68 ± 0. 17)] in the rat hippocampus compared with the CUMS group (P <0.01). Conclusion The up-regulation of the Notch1 pathway with chronic fluoxetine administration might partly contribute to increased neurogenesis in the rat hippocampus with depression.
