温阳解郁汤对抑郁症模型大鼠下丘脑-垂体-肾上腺轴影响及调控机制的研究

Depression is a group symptom of mood disorders as a main symptom caused by each kind of reason。Most of the treatment of depression drugs established on the basis of the "monoamine hypothesis"，in recent years due to the limitations of it the pathophysiological mechanisms other than the monoamine neurotransmitter has become the focus of depression research，among them the the role of neuroendocrine system related to stress receiving the most attention in the pathogenesis of depression。Hypothalamus-pituitary-adrenal axis ( HPA axis ) is the key to adjust stress reaction system，HPA axis dysfunction is considered to be a common pathway for many signs and symptoms of depression。Previous studies showed that Wen Yang Jie Yu Decoction can significantly shorten the immobility time of the tail suspension test and forced swimming test in mice，but the prescription anti-depressant mechanism of action is unclear。Through preliminary clinical observation we found that Wen Yang Jie Yu Decoction can regulate plasma CORT levels in patients with depression，and we believe that the prescription may have played a role in regulating the HPA axis。In the above understanding，in this project we will further study its function and related regulating pathways of Wen Yang Jie Yu Decoction on depression animal model by radioimmunoassay method、 RT-PCR method and immunohistochemical method from the whole、 organ and molecular levels，trying to combine theory and practice and further clarify the characteristics and mechanism of the antidepressant effect of the prescription。

抑郁症是由各种原因引起的以抑郁为主要症状的一组心境障碍，目前大部分治疗抑郁症的药物都是建立在"单胺类假说"基础上，近年来由于其局限性单胺类递质以外的病理生理学机制已成为抑郁症研究的焦点。其中应激相关的神经内分泌系统在抑郁症发病中的作用最受关注，下丘脑-垂体-肾上腺轴（HPA轴）是调节应激反应的关键系统，HPA轴功能的异常被认为是许多抑郁症症状和体征产生的共同通路。前期研究表明温阳解郁汤能显著缩短悬尾试验和强迫游泳试验小鼠悬尾和游泳不动时间，但该方抗抑郁作用的机制尚不明确。从我们前期临床观察温阳解郁汤能调控抑郁症患者血浆CORT水平来看，可能是发挥了对HPA轴的调控作用。基于上述认识，本课题将从整体、器官和分子水平采用放射免疫法、RT-PCR法及免疫组化等方法对"温阳解郁汤"调控抑郁症动物模型HPA轴的作用及相关通路进行深入研究，力图从理论与实践的结合上进一步明确该方抗抑郁作用特点与机制。

温阳解郁汤以中医解郁理论为基础，对阳虚型抑郁症方证对应。本研究构建慢性不可预知应激抑郁模型（CUMS）大鼠，研究该方剂对CUMS大鼠下丘脑-垂体-肾上腺轴（HPA轴）的影响。结果发现：（1）CUMS模型大鼠较正常大鼠悬尾和游泳不动时间明显延长；旷场穿格次数减少；血皮质酮（CORT）和促肾上腺皮质激素（ACTH）水平升高；下丘脑促肾上腺皮质激素释放激素（CRH）mRNA表达水平和垂体糖皮质激素受体（GR）mRNA表达水平升高。（2）灌胃温阳解郁汤的CUMS模型大鼠较灌胃生理盐水的CUMS模型大鼠悬尾和游泳不动时间明显缩短；旷场穿格次数增加；血皮质酮（CORT）和促肾上腺皮质激素（ACTH）水平降低；下丘脑促肾上腺皮质激素释放激素（CRH）mRNA表达水平和垂体糖皮质激素受体（GR）mRNA表达水平降低，并能降低高糖皮质激素水平对大脑海马组织的损伤。这些研究结果显示，温阳解郁汤能够改善CUMS模型大鼠的抑郁行为，这一改善可能与调节HPA轴相关激素表达水平有关。