宫颈上皮内瘤变证素辨证及其相关蛋白质组学基础研究

Cervical intraepithelial neoplasia (CIN) is a group of precancerous lesions which is closely related with invasive cervical cancer. It reflects the entire development process of cervical carcinoma. CIN has no specific clinical features, and the main symptoms and signs is not obvious. It is a relatively lengthy process from CIN to cervical cancer, which normally takes about 10 years. It contains subside or reverse the outcome, maintenance, and cancer transplantation. At present, the western medicine treatment includes follow-up, medication, physical therapy and surgery. Conization of cervix has been the most common cervical treatment modality for high grade CIN. The post-treatment rate of CIN falls with time; however, even women with negative margins are at risk for disease residual or recurrence. According to literatures and textbooks, it is not difficult to find that the Traditional Chinese Medicine treatment for CIN has no uniform standard type. However, the traditional Chinese medicine plays a vital role in improving symptoms and signs and slowing the progress of the cancer transplantation. Based on our previous study, we aim to establish a standardized program for associated clinical information collection during the diagnostic course of cases with CIN by means of Four Diagnostic Methods in order to set up the related standards for quantitative pattern differentiation among CIN cases based on the principles of pattern elements. Our research also identifies differential proteins in cervix tissue with and without CIN using two-dimensional electrophoresis (2-DE) and MALDI-MS/MS. The differential proteins identified may play important roles in the presence and advance of CIN. We explore the molecular basis underlying these patterns of CIN on the basis of proteomics carried out with cervix tissue.

宫颈上皮内瘤变（CIN），属于中医"带下病"范畴。现代医学对宫颈病变的研究已经深入到分子水平，现有治疗CIN的主要手段仍是清除存在病变上皮组织的宫颈锥形切除术，对导致宫颈病变发生发展的人乳头瘤病毒感染，无有效抗病毒药物，且锥切术后CIN的残留和复发率有逐年增高的趋势，给进一步的随访和治疗带来一系列难题。中医学"未病先防、已病防变"理念在CIN防治方面有独特优势，但至今中医界关于CIN领域的规范化研究鲜见。基于本课题组在CIN中医证型、演变规律及流行病学的前期研究基础，我们采用证素计量辩证法探讨CIN四诊信息的规范化采集方案，在此基础上建立CIN证素计量辨证的相关标准。采用亚细胞差异蛋白质组学策略，探索CIN组织与正常宫颈组织蛋白质组表达图谱的差异，从蛋白质水平阐明CIN发生发展机制，且对CIN常见证型的相关分子本质进行初步探讨，建立"证候－蛋白质表达谱"，为中医辨证客观化提供依据和方法。

采用证素计量辩证法探讨CIN 四诊信息的规范化采集方案，在此基础上建立 CIN 证素计量辨证的相关标准；利用阴道镜对CIN患者按照RCI评分步骤进行评分，发现CIN 的证型分布中湿热证(占63. 8% ) 为最常见的临床证型，脾虚证次之，阴虚夹湿证最少，CIN 阴道镜 ＲCI 评分与 CIN不同中医证型间有相关性；另外，基于阴道镜显像技术观察，发现高级别CIN阴道镜下宫颈局部征象望诊以宫颈颜色、宫颈病变部位血管颜色、质地与中医证有关，其证的分布特点为常见病位证素为胞宫，其次为肝、脾、肾，常见病性证素为湿，其次为热、阴虚、血瘀。采用亚细胞差异蛋白质组学策略，研究CIN组织与正常宫颈组织蛋白质组表达图谱，但发现二者之间无明显差异。. 本研究为CIN 的中医辨证分型提供参考标准，并为阴道镜征象应用于中医辨证资料提供理论依据，延伸了妇科望诊的形式与内容，可使临床诊疗更具有针对性,为中医防治CIN提供一定的指导。