基于网络药理学方法的中西医结合治疗多囊卵巢综合症作用机制

Polycystic ovary syndrome is a common endocrine disease in clinical department of gynecology. Traditional Chinese medicine as well as western medicine thinks it as a complex diseases. The treatment effect with pure western medicine or Chinese medicine is not ideal. So analysis of drug intervention and influence of pathology on the basis of system biology by network Pharmacology undoubtedly is an important strategy to study the complex diseases and their treatments methods such as PCOS. Firstly, the project will clean the PCOS prescriptions from doctors of all dynasties and establish the database of PCOS by data mining. We will screen the basic medicines for PCOS on the base of syndrome differentiation. Then we will set up a network model of Chinese traditional medicine function, western medicine （Clomiphene ）function and PCOS disease which can bring about the effective connection between component - target - channel - disease. This will reveal the main mechanism of core group medicine for PCOS with different symptoms ,and will interpret traditional Chinese medicine syndrome differentiation as well as it's mechanism of multiple components, multiple targets and multiple ways . This will also interpret the advantage of combining traditional Chinese medicine with western medicine in treating PCOS from the aspects of molecules, and Using network model to predict potential targets of PCOS and effective new prescriptions. All of this can help us to combine traditional Chinese medicine with western medicine in the clinical for PCOS reasonably and provide the basis of development of new drugs in the future.

多囊卵巢综合征（Polycystic Ovary Syndrome，PCOS）是妇科临床常见的内分泌疾病。中医或西医都认为PCOS属于复杂性疾病，单纯的西医或中医治疗效果并不理想。采用网络药理学方法从系统生物学的角度来分析药物对病理的干预和影响，无疑是研究PCOS这种复杂疾病及其治疗方法的重要策略。项目首先用数据挖掘的方法对历代医家治疗PCOS的方药进行清洗并建立数据库，在辨证分型的基础上筛选出中药治疗PCOS的核心组药；然后采用网络药理学方法建立中药作用网络、西药（克罗米芬）作用网络和PCOS疾病网络模型，实现成分-靶点-通路-疾病之间的有效关联；揭示不同证型核心组药治疗PCOS的主要机制，阐释中医辨证论治和多成分、多靶点、多途径的作用机理；从分子学层面阐释中西医结合治疗PCOS的优势；利用网络模型预测PCOS潜在的作用靶点和有效新方。有助于我们今后临床合理运用中西医治疗PCOS及其新药开发。

多囊卵巢综合征（Polycystic Ovary Syndrome，PCOS）是妇科临床常见的内分泌疾病。中医或西医都认为PCOS属于复杂性疾病，单纯的西医或中医治疗效果并不理想。课题采用网络药理学方法从系统生物学的角度来分析药物对病理的干预和影响。首先用数据挖掘的方法对历代医家治疗PCOS的方药进行清洗并建立数据库，数据显示肾虚血瘀型、痰湿型和肝经湿热型为主要中医证型，对三种证型的核心药物进行成分-靶点-通路-疾病网络药理学分析，发现不同证型核心组药治疗PCOS的靶点和通路仍存在差异，但多成分、多靶点、多途径是中医治疗PCOS的主要特征；然后选取肝经湿热型代表方剂龙胆泻肝汤进行体内外药物实验验证，采用6周龄的Wistar大鼠，将来曲唑（Letrozole, LE）（1mg/kg/d）溶于1%羧甲基纤维素钠（CMCNa）中，灌胃28d，诱导大鼠PCOS模型，同时给予克罗米芬（Clomiphene, CC）和龙胆泻肝汤。28d后，将大鼠处死，对各组大鼠卵巢进行形态学观察，用Elisa法测定其血清中黄体生成素（FSH）、促卵泡素（LH）、睾酮（T）、雌二醇（E2）的含量并进行分析。从体内实验初步研究龙胆泻肝汤等药对大鼠PCOS模型是否具有明显的治疗作用。随后用血清药理学的方法进行体内实验，用含药血清处理中国仓鼠卵巢细胞系CHO-K1，观察其对细胞存活率的影响。继而对大鼠卵巢组织进行蛋白质组学分析，得到药效靶点，运用de novo的网络药理学方法构建龙胆泻肝汤治疗PCOS药效网络，发现龙胆泻肝汤可能通过LDHB，RPL5，HIST1H2BM，GPI，GLUD1的分泌对核糖体，糖酵解，卵母细胞减数分裂以及Hippo等信号通路进行调控，继而发挥延缓PCOS发生发展的作用，为龙胆泻肝汤治疗PCOS的临床应用提供理论支持。