基于NEI网络评价青娥丸治疗更年期综合征的药效学研究

Menopausal syndrome is a common disease of women, and is usually treated with hormone replacement therapy (HRT) in the clinical. However, in view of the risk of HRT, Seeking more safe and effective drugs has become a focus in this research field. Due to the single class of phytoestrogen often has weak active, Traditional Chinese prescriptions with multi-component and multi-target have attracted much more research interest.The principle for the treatment of menopausal syndrome in TCM is warming kidney. Qing'E pill has the function of invigorating the kidney, is a compound prescription comprised of four ingredients, Eucommniae Cortex, Psoraleae Fructus, Juglandis Semen and Garlic Rhizoma. Qing'E pill is rich in phytoestrogens such as flavonoids and coumarin, and also contains other compounds such as lignans and iridoid, which can relieve menopausal symptoms from the multi-channel and multi-target.Because the symptoms of menopause syndrome are widely distributed and difficult to fully evaluate by a single index, we applied the Nerve-Endocrine-Immune (NEI) network as the evaluation system for the efficacy of menopause syndrome, which is closely related with menopause syndrome and can be used to reflect the whole condition of the body.This study intends to evaluate the efficacy of Qing'E pill on the treatment of menopausal syndrome based on the NEI network by the ovariectomized rats, and then understand in depth the advantage of multi-component and multi-target for the Traditional Chinese prescription by compared with the efficacy of nilestriol and Isoflavones.

更年期综合征是女性常见病症，临床上多采用激素替代疗法(HRT)，但鉴于HRT的风险性，寻求更为安全的有效药物已成为该领域的研究热点。相比活性较弱的单一类别的植物雌激素，多成分多靶点作用的中药复方显然更具优势。中医以温补肾阳为更年期综合征的主要治则，青娥丸为补肾良方，由杜仲、补骨脂、核桃仁和大蒜组成，除含有丰富的黄酮类和香豆素类等植物雌激素外，还含有木脂素类、环烯醚萜类等成分可多途径多靶点缓解更年期症状。由于更年期综合征的症状分布广泛，单一指标很难全面反映疗效，因此我们引入与更年期综合征密切相关的神经-内分泌-免疫(NEI)网络，能够反映机体的整体状况，是评价更年期综合征疗效的理想指标。本研究拟通过青娥丸对去势大鼠进行干预，基于NEI网络全面评价青娥丸治疗更年期综合征的疗效，并通过与尼尔雌醇（雌激素）和大豆异黄酮（单一类别植物雌激素）的药效进行对比，深入剖析中药复方多成分多靶点的治疗优势。

更年期综合征的症状分布广泛，单一指标很难全面反映药物对更年期综合征的疗效，因此本项目以神经-内分泌-免疫(NEI) 网络的表达作为反映更年期综合征机体状况的评价指标，全面评价青娥丸和对照药（戊酸雌二醇和染料木黄酮）对去势大鼠NEI网络的影响，深入解析中药复方多成分多靶点的治疗优势。结果显示，去卵巢大鼠整个NEI网络相比正常大鼠严重失衡，而药物对失衡的NEI网络均有不同程度的改善，其中戊酸雌二醇主要对激素和神经递质进行调节，而青娥丸主要对甲状腺轴、肾上腺轴、血管紧张素-醛固酮系统、免疫调节因子进行调节，染料木黄酮对NEI网络的调节作用介于青娥丸和戊酸雌二醇之间。整体水平上，青娥丸对NEI网络调节作用最为明显，与正常对照组的相似度最高。以上结果提示，青娥丸可全面改善更年期失衡的NEI网络，在治疗更年期综合征方面具有较高的开发价值。因此，我们通过文献数据，构建了更年期综合征标准治疗的药效尺度，以此为基准，评估了青娥丸的临床开发价值。结果显示青娥丸起效较慢，符合典型的植物雌激素的疗效特征，但疗效高于大豆异黄酮，若以安慰剂为对照开展随机对照试验，可获得较高的试验成功率。通过计算机模拟，我们发现疗程和安慰剂效应是决定青娥丸临床试验成功的关键影响因素，12周以上疗程和采用安慰剂导入试验设计可有效提高青娥丸的试验成功率。综述所述，该项目通过引入符合中医药整体治疗优势的NEI网络，对青娥丸的疗效特点进行了全面评价，并结合文献数据，将青娥丸的临床疗效与标准药物进行对比，评估中医药的临床开发价值，以上研究思路和研究方法，可为同类中医药临床开发提供有效参考。

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