行为缺损抑郁大鼠脑环磷酸腺苷含量及蛋白激酶C表达的变化

Change of cyclic adenosine monophosphate concentration and PKC expression in behavioral deficit-induced depression rat brain

目的 在第二信使水平研究抑郁症发病的生化机制及抗抑郁药帕罗西汀的药理作用机理。方法 15只Sprague Dawley雄性大鼠随机分为抑郁模型组 5只 ,帕罗西汀治疗组 5只 ,正常对照组 5只。采用行为限制方法建立应激诱导行为缺损抑郁模型 ,连续 7日将所有动物绑缚在特制的观察笼中 ,第 7天行为限制 2 4h后对各组大鼠进行旷场试验 ;旷场试验后帕罗西汀组每天腹腔注射盐酸帕罗西汀 (3mg·kg-1·d-1) 1次 ,模型组、对照组每天腹腔注射等体积生理盐水 1次 ,均持续 14天。用放射免疫分析方法测定大鼠脑皮层环磷酸腺苷 (cAMP)的含量 ,用蛋白质免疫印渍法检测脑皮层蛋白激酶CβⅡ (PKCβⅡ )的表达水平。结果 抑郁大鼠脑皮层cAMP含量 (0 0 14± 0 0 0 1)pmol/mg ,低于正常对照组 (0 10 3± 0 0 6 4 )pmol/mg ,P <0 0 5 ;PKCβⅡ蛋白表达 (7± 4 ) % ,较对照组 (2 2± 4 ) %减弱 ,P <0 0 1。用帕罗西汀治疗 2周后 ,帕罗西汀治疗组大鼠脑皮层cAMP含量较治疗前无明显变化 (P >0 0 5 ) ,但PKCβⅡ蛋白表达则明显增强 [(34± 5 ) % ],与接受生理盐水腹腔注射的抑郁模型组大鼠[(7± 4 ) % ]的差异有非常显著性 (P <0 0 1)。结论 抑郁发生可能与第二信使腺苷酸环化酶 环磷酸腺苷 (AC cAMP)、磷酸肌醇

Objective In order to investigate the mechanism of depression induced by behavioral deficits and antidepression of paroxetine in the level of the second message system. Methods Fifteen male Sprague Dawley rats were randomly divided into three groups: depression model, paroxetine treated and control group Rats were immobilized for 2 hours per day in 7 days to build up depression model The brain concentration of cyclic adenosine monophosphate (cAMP) was determined with 3H radioimmunoassay, and expression of protein kinase C βⅡ(PKC βⅡ) with western blotting Results The cAMP concentration [(0 014±0 001)pmol/mg] and expression level of PKC β Ⅱ in the depression model rats brain were significantly lower than that in control group [(0 103±0 064) pmol/mg, P <0 05; (22±4)%, P <0 01] After 2 week paroxetine treatment, PKC β Ⅱ expression in cortex obviously increased ( P <0 01), but the cAMP concentration in cortex was unchanged ( P > 0 05) Conclusion It is suggested that the suppression of second messenger pathways, including AC cAMP and PI Ca 2+ systems, may be involved in the mechanism of depression The antidepressive effect of paroxetine may be related to PI Ca 2+ pathway