柴欢宁神颗粒对肝郁失眠证候大鼠模型行为学及下丘脑-垂体-肾上腺轴的影响

Effects of Chaihuan Ningshen Granules on the behavior and hypothalamic-pituitary-adrenal axis of rats with insomnia with syndrome of stagnation of liver qi

目的探讨柴欢宁神颗粒对多因素复合法致肝郁失眠证候模型大鼠的行为学和下丘脑-垂体-肾上腺(HPA)轴的影响。方法将70只SD大鼠雌雄各半,随机分为空白组,模型组,柴欢宁神颗粒高、中、低剂量组(2.25、1.125、0.5625 g/kg),解郁安神组(1.25 g/kg),艾司唑仑组(0.5 mg/kg)。除空白组外,其余各组均采用束缚+夹尾刺激+PCPA多因素制备肝郁失眠证候的大鼠模型。各给药组经灌胃给予相应的药物,空白组及模型组给予等体积的生理盐水,每日1次,连续14 d。分别于实验第0、7、14、21天测试各组大鼠的体重、糖水消耗量、睡眠状况及水迷宫定位航行和空间搜索能力等指标评价大鼠的行为学。后采用酶联免疫吸附测定法(ELISA)检测大鼠下丘脑中促肾上腺皮质激素释放激素(CRH)、血浆促肾上腺皮质激素(ACTH)和血清皮质醇(CORT)水平。结果与空白组比较,模型组大鼠体重、糖水消耗量、睡眠时间、空间搜索能力明显降低,下丘脑CRH、血浆ACTH、血清CORT及水迷宫定位航行时间升高,差异有统计学意义(P<0.05)。经给药干预后,与模型组比较,各给药组可增加大鼠的体重、睡眠时间、糖水消耗量、穿越平台的次数,同时降低大鼠下丘脑CRH、血浆ACTH、血清CORT的水平,以及定位航行的时间,差异有统计学意义(P<0.05)。结论柴欢宁神颗粒可明显改善肝郁失眠证候模型大鼠的行为学,延长睡眠时间,其机制可能与调节改善HPA轴功能的亢进有关。

Objective To investigate the effects of Chaihuan Ningshen Granules on the behavior and hypothalamic-pi- tuitary-adrenal （HPA） axis of rats with insomnia with syndrome of stagnation of liver qi induced by muhifactor combi- nation therapy. Methods Seventy SD rats （half male and half female） were randomly divided into 7 groups： blank group, model group, high, medium and low dose of Chaihuan Ningshen Granules groups （2.25, 1.125, 0.5625 g/kg）, Jieyu Anshen Granules group （1.25 g/kg）, Estazolam group （0.5 mg/kg）. Except for the blank group, rats in each group were es- tablished for the model with syndrome of stagnation of liver qi by multifactorial stimulation including tie, pinch-tail and PCPA. Each administration group was treated daily with an oral infusion of corresponding drug, whereas, the blank group and the model group were given equal volume of saline once a day for 14 days. All rats were tested on the 0, 7th, 14th, 21st d for body weight, sugar consumption, sleep status, water maze navigation and spatial search ability to evaluate the behavior of rats, The levels of corticotropin-releasing hormone （CRH）, adrenoeorticotropic hormone （ACTH） and serum cortisol （CORT） in the hypothalamus of rats were detected by enzyme linked immunosorbent assay （ELISA）. Results Compared with blank group, the body weight, sugar consumption, sleep duration and spatial search ability of the model group were significantly decreased, while the hypothalamic CRH, plasma ACTH, serum CORT and water maze positioning sailing time were marked ly increased （P 〈 0.05）.Compared with the model group, all medicine groups could significantly increase body weight, sleep duration, consumption of sugar water and the number of crossing platform （P 〈 0.05）, meanwhile decrease the levels of the hypothalamic CRH, plasma ACTH and serum CORT, as well as water maze positioning sailing time, the differences were statistically significant （P 〈 0.05）. Conclusion Chaihuan Ningshen Granules can remarkably improve the behavior of rats with insomnia with syndrome of stagnation of liver qi, and prolong their sleep time, the mechanism underlying this event is mainly dependent on the improvement effect of Chaihuan Ningshen Granules on the function of HPA axis.