苍艾挥发油对大鼠抑郁样行为的影响及机制研究

目的?研究苍艾挥发油（Volatile oil of Cang Ai，VOCA）对不可预知慢性温和应激所致的大鼠抑郁样行为的影响及其可能的作用机制。方法?将40只SD大鼠，随机分为4组，正常对照组、模型对照组、阳性药组（氯米帕明，20?mg/kg）和苍艾挥发油组（14.6?μL/kg）各10只；后3组大鼠均采用6种不同刺激方式复制慢性不可预知温和应激模型(CUMS)。在CUMS造模第15~42天进行药物干预，除阳性药灌胃给药外，其他各组均雾化吸入相应剂量的药物或溶媒。于造模后第21、28、35、42天进行体质量、食量和毛态检测，造模结束后的第1天进行旷场实验和蔗糖偏好实验，以评价苍艾挥发油对应激所导致的抑郁样行为的作用。用免疫荧光染色检测大鼠海马齿状回BDNF阳性细胞数、蛋白免疫印迹法检测大鼠海马中突触囊泡蛋白(Synaptophysin)和突触后致密物质-95(PSD-95)的蛋白表达水平。结果?与模型组比较，VOCA可明显增加模型大鼠的水平运动总路程、穿行格子数和移动速度，同时缩短静止时间（P<0.01），提高蔗糖偏好度（P<0.05）。VOCA在给药第7、14、21和28天可显著增加造模动物体质量增幅和进食量（P<0.05~0.01），毛态评分则明显低于模型组（P<0.01）。同时，VOCA能够明显增加海马齿状回中BDNF阳性细胞数和海马组织中Synaptophysin表达量（P<0.01）。结论?苍艾挥发油对抗大鼠慢性不可预见应激抑郁的机制可能与增加BDNF含量进而增加突触囊泡膜蛋白表达从而改善突触传递效能有关。 

The Study on the Anti-Depression Effect and Mechanism of Volatile Oil of Cang Ai

OBJECTIVE?To discuss the antidepressant effect and related mechanism of the Volatile oil of Cang Ai(VOCA). METHODS?40 Male Sprague-Dawley rats were randomly divided into 4 groups on average．They were normal control group， model group， VOCA group（14.6?μL/kg） and clomipramine group（20?mg/kg）. Then the rats in later three groups were exposed constantly to 6 types of chronic and mild unpredictable stressors for 42 d. VOCA， solvent or clomipramine were administrated by aerosol inhalation or gavage from d15 to d42.Body weight， food intake and coat state were measured on d21， d28， d35 and d42. Open field test and sucrose preference test were applied to elucidate the antidepressant effects of VOCA at the first day after the modeling. Immunofluorescence staining was used for detection of BDNF positive cells in hippocampal dentate. Western blotting was used in the observation of the expression of Synaptophysin and PSD-95 proteins. RESULTS?Compared with model group， VOCA could increase the total horizontal movement， number of squares traveled and moving speed of CUMS rats， while shorten the rest time significantly (P<0.01). The rats' preference for sucrose solution was obviously increased in VOCA group(P＜0.05). The weight gain amplitude and food take of rats in VOCA group were also increased on the 7th， 14th， 21th and 28th day of administration（P＜0.05，P<0.01). At the same time， the coat state scores of the rats which treated with VOCA decreased significantly （P<0.01）. VOCA significantly increased the number of positive cells of BDNF and promoted the expression of Synaptophysin protein(P＜0.05). CONCLUSION?The antidepressant effect of the VOCA may be related to modulate the expression of BDNF and the critical proteins associated with synaptic structural and plasticity in the hippocampus．