盆腔炎性疾病后遗症大鼠非手术建模评价及证候属性的研究

The modeling method of sequelae of pelvic inflammatory disease sequelae (SPID) animal model was established with laparotomy in the domestic，which did not match the process of clinical disease and was not explicit for syndrome properties of TCM．The modeling method of similar model was to ascending infection through the vagina which matched the process of clinical disease but most of model was attributable to pelvic inflammatory disease．The research group carried out long-term scientific research on prevention and treatment for SPID，which included syndromes composition、efficacy evaluation、prescription development and animal models that consist of model approach and its intervention related to inflammatory cytokines、immunomodulatory、antioxidant adhesion study．Based on these problem，The study proposed the new concept of the non-surgical modeling SPID rats model which was characterized with 8 pathological type of three tissues and organs(fallopian tubes、ovaries、pelvic connective tissue) according to clinical pathology and its basic syndromes which was defferentiated from different modeling method．At the same time，that concept also suggested that the construction methods of that model should be consistent to the clinical disease process．According to the concept，the study will introduce diseases incentives of exercise-induced fatigue which is derived from TCM theory of"evil infection with lack of righteousness"，increase exogenous pathogens and single source of infection according to changes in the types of clinical pathogens，give ascending infection through vaginal according to clinical infection route of SPID，detect repeatedly the model effect by means of pathological index(TNF-α，IL-1、IL-2、IL-6、IL-8、IL-10)、inflammatory and proliferative repair indicators(TGF-1、MMP-2、VEGF）．Then，the methods of animal characterized syndrome research will be used to the model for its syndrome properties of TCM that includes objectiving characterized syndrome、mathematical statistics and proving to the contrary with Chinese herbs．Based on the above study，we will established a new SPID rats model and its based methods with consistent to SPID clinical disease characteristics．We will also prove the model syndrome properties of TCM and its methods of evaluation．The research will play a key supporting role of laying the internationally recognized SPID research platform of TCM．

国内盆腔炎性疾病后遗症(SPID)开腹手术动物模型，与临床发病不符且证候属性不清，国外经阴道上行感染法为盆腔炎性疾病模型。基于此，在前期SPID模型炎症和免疫修复等指标分析及临床证候、疗效评价基础上，本研究提出新的非手术SPID模型概念，其建模应符合临床发病过程、判定应为输卵管、卵巢、盆腔结缔组织3个部位的8种临床病理分型，应有基本证候和不同构模的差异。据此，本研究以正气不足而感邪，引入大鼠运动性疲劳诱因，依SPID临床病原体种类，增设外源性病原体和单一感染源，设立比拟临床的阴道上行感染，结合炎症因子(TNF-α、IL-1、IL-2、IL-8、IL-10）及增生粘连指标(TGF-1、MMP-2、VEGF），多时点检测成模效果；并依中医辨证理念比拟临床证候，纳入SPID大鼠动物表征，结合方药反证，明确SPID大鼠证候属性及其评价方法。这对奠定SPID中医药研究平台，将发挥关键支撑作用。

国内盆腔炎性疾病后遗症(SPID)开腹手术动物模型，与临床发病不符且证候属性不清，国外经阴道上行感染法为盆腔炎性疾病模型。基于此，在前期SPID模型炎症和免疫修复等指标分析及临床证候、疗效评价基础上，本研究提出新的非手术SPID模型概念，其建模应符合临床发病过程，判定应为输卵管、卵巢、盆腔结缔组织3个部位的8种临床病理分型（包括输卵管（增粗、阻塞、积水），输卵管卵巢（粘连、肿块、囊肿），盆腔结缔组织（增生、粘连）），应有基本证候和不同构模的差异。据此，本研究以正气不足而感邪，引入大鼠疲劳及饥饿诱因，设立比拟临床的阴道上行感染，通过检测模型大鼠的体态行为，阴道分泌物，卵巢、输卵管、盆腔结缔组织的大体形态学和显微形态学改变，检测外周血以及各组织匀浆中的炎症调控因子和与组织增生修复密切相关指标，多时点检测非手术造模成模效果；并依中医辨证理念比拟临床证候，纳入SPID大鼠动物表征，结合方药反证，明确SPID大鼠证候属性及其评价方法。结果显示，SPID大鼠非手术造模成功；非手术建模SPID大鼠模型以气滞血瘀证占绝对优势。各组药物干预后，各实验组大鼠指标均趋向正常大鼠的表达水平，差异有统计学意义；对比4种干预，逍遥舒坤汤更能显著降低CD8、CD161、Th-17、Foxp3、IL-4、IL-6、IL-17、IL-10、TNFα、TGFβ、MMP2、VEGF及其NKG2D的表达，升高CD3、CD4及其NKG2A表达，差异有统计学意义。施加疲劳及饥饿诱因后经阴道种植感染源的非手术SPID大鼠模型更符合临床发病特征，是更适宜SPID防治研究的动物模型；结合SPID公认方剂反证评价，明确该种方法建立的SPID大鼠模型，其证候属性以气滞血瘀证占绝对优势。本研究填补了SPID非手术动物模型建模及其证候属性研究领域的空白，为探讨SPID发病机制及中医药治疗SPID的机理研究奠定了基础。