一解合方对更年期抑郁症大鼠海马、皮质5-HTR1A表达的影响

Effect of Yijiehefang on Protein Expression of 5-HTR1A in Hippocampus and Cerebral Cortex of Rats with Perimenopausal Depression

目的:探讨一解合方治疗更年期抑郁症的作用机制。方法:对雌性成年大鼠采用去势+孤养+改良的慢性不可预见应激建立更年期抑郁症模型;将去势大鼠随机分为更年期组、模型组、西药组(百优解联用雌激素)、中药组(一解合方),并以假手术组作对照。采用免疫组化法检测海马、皮质5-HTR1A的蛋白表达;采用放射免疫分析法(RIA)测定血清CORT,观察对比分析各组大鼠上述指标的变化。结果:中药组大鼠海马、皮质的5-HTR1A蛋白表达水平显著高于模型组、西药组(P<0.01);中药组大鼠血清CORT含量低于模型组,差异极显著(P<0.01),高于假手术组,但无显著性差异(P>0.05),低于西药组,差异显著(P<0.05)。结论:应激后5-HT1A受体结合下降可能是由于糖皮质激素增高所致,一解合方可通过影响海马、皮质突触后5-HTR1A的蛋白表达水平调节HPA轴而发挥抗抑郁作用,海马、皮质突触后5-HTR1A作为药物治疗的新靶点成为可能。

Objective： To explore the mechanism of Yijiehefang in treating perimenopausal depression. Methods： Perimenopausal depression model was established in female adult rats by using castration and chronic unpredictable stress. Castrated rats were divided into four groups： menopause group, model group, western medicine group （fluoxetine plus estrogen）, and Chinese medicine group （Yijiehe- fang） . Sham operation group was considered as control. Tile protein expression of serotonin receptor- 1A （5 - HTR1A} in hippocam- pus and cerebral cortex was analyzed by immanohistochemical method, and the levels of serum Cort were detected by radioimmunoassay （RIA） method. Changes of above mentioned parameters were observed. Results： 1. The protein expression levels of 5 - HTR1A in hip- pocampus and cerebral cortex in Chinese medicine group were obviously higher than that of model group and western medicine group （ P 〈 0.01 ） . 2. The content of serum Cort in Chinese medicine group was remarkably lower than that of model group and western medicine group （ P 〈 0.01 or P 〈 0.05）, but higher than that of sham operation group with no significant difference （ P 〉 0.05） . Conclusion： The decreased 5 - HTR1A in hippocampus and cerebral cortex might result of higher Cort in serum. Yijiehefang may regulate the Hy- pothalamus- pituitary- adrenal （HPA） axis by affecting protein expression of 5 - HTR1A, and plays a role of anti - depression. The serotonin receptor- 1A may be promisingly developed as a new target for anti - depression medicine.