Abstract：
Premenstrual syndrome(PMS) lacks a highly consistent and feasible animal model that aligns with diagnostic and therapeutic standards in both traditional Chinese medicine(TCM) and western medicine, resulting in a lack of reliable experimental carriers for studying its pathogenesis and pharmacological effects. This study aims to systematically analyze the biological implications of PMS from the perspective of the "disease-syndrome-symptom" correlation and establish preparation and evaluation methods for an improved animal model of this disease. Firstly, clinical symptom gene sets related to the Qi stagnation syndromes due to liver depression and blood stasis in PMS in both modern medicine and TCM diagnostic standards were collected through GeneCards, DisGeNET, Mala-Cards, and the System of Foundational Diagnostic Association(SoFDA) database, as well as published literature. Based on the interaction information between genes, a "disease-syndrome-symptom" correlation network of PMS was established. Based on data mining results, an improved rat model of PMS was prepared by combining chronic restraint stress with the classical progesterone-withdrawal mo-del to simulate emotional depression caused by external environmental stimuli during the clinical onset process, inducing pathological damage from both physiological and emotional dimensions. The evaluation of the improved model before and after modification included open field experiment scores, organ indices, ovarian pathological changes, serum levels of estradiol(E_2), follicle-stimulating hormone/luteinizing hormone(FSH/LH), 5-hydroxytryptamine(5-HT), dopamine(DA), norepinephrine(NE), as well as coagulation parameters and hemorheology indexes. By calculating the degree, betweenness, and closeness centrality of nodes in the "disease-syndrome-symptom" correlation network, 163 core genes with topological importance were identified. Further biological function mining results indicated that core genes in PMS mainly participated in the regulation of the "nervous-endocrine-immune" system and pathways related to circulatory disorders. Mapping analysis of clinical phenotype symptom gene sets suggested significant correlations between core genes in PMS and depressive symptoms and pain symptoms caused by blood stasis. Compared with the simple progesterone withdrawal model, rats subjected to combined injections and restraint stress showed more significant abnormalities in open field experiment scores, ovarian tissue pathology, serum neurotransmitter levels of 5-HT and DA, as well as serum hormone levels of E_2 and FSH/LH. The modified modeling conditions exacerbated the pathological changes in blood rheology, coagulation function, and red blood cell morphology in model rats, confirming that the improved rat model could characterize the "nervous-endocrine-immune" system disorder and circulatory system disorders in the occurrence and progression of PMS, consistent with the clinical diagnostic and therapeutic standards of both TCM and western medicine. The establishment of the improved rat model of PMS can provide a reliable experimental carrier for elucidating the pathogenesis of PMS and discovering and evaluating therapeutic drugs. It also provides references for objectively reflecting the clinical characteristics of PMS in TCM and western medicine and precision treatment.
摘要：
经前综合征（PMS）缺乏一个高度一致和可行的动物模型，符合中医（TCM）和西医的诊断和治疗标准，导致缺乏可靠的实验载体来研究其发病机理和药理作用。本研究旨在从病证相关的角度系统分析经前综合征的生物学意义，并建立该疾病改良动物模型的制备和评价方法。首先,通过GeneCards收集现代医学和中医诊断标准中与PMS中肝郁血瘀气滞证相关的临床症状基因集，DisGeNet,Mala-Cards,和基础诊断协会系统(SoFDA)数据库，以及出版的文献。根据基因之间的相互作用信息，建立了经前综合征的病证相关网络。根据数据挖掘结果，通过将慢性束缚应激与经典的孕酮戒断模型相结合，制备了一种改良的PMS大鼠模型，以模拟临床发作过程中外界环境刺激引起的情绪抑郁。从生理和情感两个维度诱导病理损伤。改进模型修改前后的评价包括野外实验得分,器官指数,卵巢病理变化，血清雌二醇（E_2）水平，卵泡刺激素/黄体生成素（FSH/LH），5-羟色胺（5-HT），多巴胺（DA），去甲肾上腺素(NE),以及凝血参数和血液流变学指标。通过计算度，中间性，以及“疾病-综合征-症状”相关网络中节点的紧密中心性，鉴定了163个具有拓扑重要性的核心基因。进一步的生物学功能挖掘结果表明，PMS中的核心基因主要参与了与循环障碍相关的神经-内分泌-免疫系统和通路的调节。对临床表型症状基因集的定位分析表明，PMS中的核心基因与血瘀引起的抑郁症状和疼痛症状之间存在显着相关性。与单纯孕酮戒断模型相比，联合注射和束缚应激的大鼠在野外实验评分中表现出更显著的异常，卵巢组织病理学,血清神经递质水平5-HT和DA，以及血清E_2和FSH/LH的激素水平。改良的造模条件加剧了血液流变学的病理变化,凝血功能，模型大鼠红细胞形态,证实改进的大鼠模型可以表征神经-内分泌-免疫"PMS的发生和进展的系统疾病和循环系统疾病，符合中医和西医的临床诊断和治疗标准。改良PMS大鼠模型的建立可为阐明PMS的发病机制、发现和评价治疗药物提供可靠的实验载体。为客观反映PMS的中西医临床特点及精准治疗提供参考。
