姜黄素预处理对慢性心理应激大鼠中枢神经的保护作用

NEUROPROTECTIVE EFFECT OF CURCUMIN ON RATS UNDER CHRONIC UNPREDICTABLE MILD STRESS

目的观察姜黄素预处理对慢性应激大鼠行为学、单胺类递质水平及血清糖皮质激素的影响,为评价姜黄素对慢性心理应激大鼠中枢神经的保护作用提供依据。方法 48只Wistar大鼠随机分为对照组、慢性应激组、氟西汀干预组、姜黄素(低、中、高剂量)干预组,每天应激前1 h灌胃给药。对大鼠进行28 d应激刺激建立慢性不可预知性慢性应激模型。旷场试验测定大鼠行为学指标;糖水试验测定大鼠"快感缺乏";高效液相-电化学检测法测定海马单胺类递质;ELISA检测血清糖皮质激素。结果慢性应激组大鼠的体质量、旷场活动性和糖水偏嗜度均明显低于对照组(P<0.05,P<0.01);海马5-HT含量下降(P<0.05),血清糖皮质激素水平升高(P<0.01)。3个剂量姜黄素组大鼠体质量于第4周分别为(310.60±21.35)、(315.60±23.73)和(319.91±18.76)g,高于慢性应激组〔(270.24±19.60)g,P<0.05〕;旷场竖立时间分别为(18.86±9.49)、(24.14±4.38)和(24.14±5.41)s,高于慢性应激组〔(11.00±9.20)s,P<0.05〕;血清糖皮质激素水平分别为(567.94±22.54)、(338.62±63.79)和(259.96±17.79)ng/L,低于慢性应激组〔(908.57±22.86)ng/L,P<0.01〕。实验后低、中剂量组海马5-HT含量分别为(1063.89±149.61)和(1340.96±42.62)ng/g,高于慢性应激组〔(941.23±80.00)ng/g,P<0.05〕。结论姜黄素预处理可改善慢性不可预知性应激大鼠抑郁状态,起到中枢神经保护作用,其作用机制可能与单胺类递质水平的增加和调节HPA轴活性有关。

Objective To observe the effect of curcumin on behavior,monoamine neurotransmitter,and serum glucocorticoid of rats under chronic unpredictable mild stress（CUMS）,in order to provide theoretical basis for assessing the neuroprotection of curcumin.Methods Forty-eight male Wistar rats were randomly divided into six groups： normal control group,stress group,curcumin groups（low,moderate,high dose）,and fluoxetine group.CUMS model of rat was established after 28 days.Curcumin（15,30,and 60 mg/kg）,and fluoxetine（5 mg/kg）were given to the rats respectively 1 h before daily stress.Body weight,sucrose solution consumption test,and open-field test were used to estimate the behavioral change.The levels of monoamine neurotransmitters,and serum glucocorticoid were detected by HPLC-ECD,and ELISA respectively.Results The body weight,open-field behavior frequency,preference for sucrose solutions,and level of 5-HT in the hippocampus in stress group were lower,while serum glucocorticoid content was higher than in control group（P0.05,or P0.01）.The body weight in 3 curcumin groups after experiment（（310.60±21.35）g,（315.60±23.73）g,and（319.91±18.76）g respectively） was higher than in stress group（（270.24±19.60）g）;open-field erection time in curcumin groups（（18.86±9.49）s,（24.14±4.38）s,and（24.14±5.41）s respectively） was also higher than in stress group（（11.00±9.20）s,P0.05）;and the serum glucocorticoid content in 3 curcumin groups（（567.94±22.54）ng/L,（338.62±63.79） ng/L,and（259.96±17.79） ng/L respectively） was lower than in stress group（（908.57±22.86） ng/L,P0.01）.The level of hippocampal 5-HT in low,moderate dose curcumin groups（（1063.89±149.61） ng/g,and（1340.96±42.62）ng/g,respectively） was higher than in stress group（（941.23±80.00） ng/g,P0.05）.Conclusion Pre-administration of curcumin may relieve the rat depressive disorder and protect central nervous system against CUMS,and the mechanism may be related to increasing the levels of monoamine neurotransmitter in the hippocampus and regulating the function of the hypothalamo-pituitary-adrenal（HPA）axis.