理虚解郁方对慢性疲劳综合征大鼠下丘脑-垂体-肾上腺轴功能及体温变化节律的影响

Influence of “Lixu Jieyu Recipe” on Hypothalamic-pituitary-adrenal Axis Function and Circadian Rhythm of Body Temperature in Rats with Chronic Fatigue Syndrome

目的:观察理虚解郁方对慢性疲劳综合征(chronic fatigue syndrome,CFS)大鼠体温节律及下丘脑-垂体-肾上腺轴(HPA轴)功能的影响。方法:将60只清洁级SD大鼠随机分为正常对照组、CFS模型组、中药治疗组及促肾上腺皮质激素释放因子拮抗剂(CRFA)组,每组15只。采用多重复合慢性应激建立CFS大鼠模型。造模同时,中药治疗组和CRFA组大鼠给予理虚解郁方药液灌胃,正常对照组及CFS模型组大鼠给予生理盐水灌胃;CRFA组大鼠按3.2 mg/kg腹腔注射CP-154526 1 ml,其余各组大鼠注射等体积的80%聚乙二醇400。各组干预时间均为30 d。采用单个余弦法分析各组大鼠体温昼夜节律的变化,比较各组大鼠下丘脑、垂体及左、右肾上腺脏器指数的变化,检测各组大鼠血浆促肾上腺皮质激素(ACTH)、皮质酮(CORT)、促肾上腺皮质激素释放激素(CRH)水平及下丘脑CRH mRNA的表达情况。结果:1与正常对照组比较,CFS模型组、CRFA组大鼠体温中值及振幅明显减小,且峰相位显著后移(P<0.05);与CFS模型组比较,中药治疗组大鼠体温中值及振幅显著增加,峰相位前移(P<0.05)。2与正常对照组比较,CFS模型组大鼠下丘脑指数、垂体指数及左、右肾上腺指数明显增高(P<0.05),CRFA组大鼠下丘脑指数亦明显增高(P<0.05);与CFS模型组比较,中药治疗组大鼠左、右肾上腺指数明显降低(P<0.05)。3与正常对照组比较,CFS模型组、CRFA组大鼠的血浆CORT、CRH水平均显著降低(P<0.05),且CRFA组大鼠的血浆ACTH水平亦显著降低(P<0.05);与CFS模型组比较,中药治疗组大鼠的血浆CORT、CRH水平显著升高(P<0.05)。4与正常对照组比较,CFS模型组、CRFA组大鼠下丘脑CRH mRNA表达明显下降(P<0.05);与CFS模型组比较,中药治疗组大鼠的下丘脑CRH mRNA表达水平显著升高(P<0.05)。结论:理虚解郁方可影响慢性疲劳综合征大鼠下丘脑CRH mRNA的表达,进而调控血浆CRH、ACTH与CORT含量,调节体温节律。

Objective： To observe the effects of＂Lixu Jieyu Recipe＂on the hypothalamic-pituitary-adrenal axis（ HPAA）function and the circadian rhythm of body temperature in rats with chronic fatigue syndrome（ CFS）. Methods： A total of 60 clean SD rats were randomly divided into normal control group,CFS model group,Chinese medicine treatment group and corticotropin releasing factor antagonist（ CRFA） group,with 15 rats in each group. The rat model of CFS was established by the multiple composite factors combined with chronic stress. The rats in the Chinese medicine treatment group and CRFA group were treated with＂Lixu Jieyu Recipe＂intragastrically,and the rats in the normal control group and CFS model group were treated with normal saline intragastrically; the rats in the CRFA group were intraperitoneally injected with CP-154526 at dose of3. 2 mg / kg,and the rats in other groups were intraperitoneally injected with 80% polyethylene glycol 400. The treatment course was 30 days. The changes of circadian rhythm of body temperature were analyzed by single consine method,the hypothalamus,pituitary and adrenal organ indexes were compared,and the levels of serum adrenocorticotropic hormone（ ACTH）,corticosterone（ CORT） and corticotropin releasing hormone（ CRH） and the expression of CRH mRNA of hypothalamus were detected. Results： ① Compared with the normal control group,the mean value and amplitude of body temperature were decreased and the peak phase shifted backward in the CFS model group and the CRFA group（ P〈0. 05）;compared with the CFS model group,the mean value and amplitude of body temperature were increased and the peak phase shifted forward in the Chinese medicine treatment group（ P〈0. 05）. ②Compared with the normal control group,the indexes of hypothalamus,pituitary and left and right adrenals organ were increased in the CFS model group（ P〈0. 05）,and the hypothalamus organ index was increased in the CRFA group（ P〈0. 05）; compared with the CFS model group,the left and right adrenals organ indexes were decreased in the Chinese medicine treatment group（ P〈0. 05）. ③Compared with the normal control group,the levels of CORT and CRH were decreased in the CFS model group and the CRFA group（ P〈0. 05）,and the level of ACTH was decreased in the CRFA group（ P〈0. 05）; compared with the CFS model group,the levels of CORT and CRH were increased in the Chinese medicine treatment group（ P〈0. 05）.④ Compared with the normal control group,the expression of CRH mRNA in hypothalamus was decreased in the CFS model group and the CRFA group（ P〈0. 05）; compared with the CFS model group,the expression of CRH mRNA in hypothalamus was increased in the Chinese medicine treatment group（ P〈0. 05）. Conclusion： ＂Lixu Jieyu Recipe＂can affect the expression of CRH mRNA in hypothalamus,and adjust the plasma levels of CRH,ACTH and CORT and the circadian rhythm of body temperature.