基于ADP-heptose/ALPK1通路研究加味二妙颗粒调节宫颈阴道微生态清除HPV的作用机制

子宫颈鳞状上皮内病变（SIL）与子宫颈浸润癌相关，高危型人乳头瘤病毒（HR-HPV）感染是SIL的原因。阴道微生态失衡是HR-HPV感染的必要条件。无清除HPV的特效药物。文献及前期研究工作表明：加味二妙颗粒能有效清除HPV；二磷酸腺苷庚糖（ADP-heptose）作为阴道菌群代谢物在HPV阴性与阳性患者宫颈阴道分泌物中存在差异；HPV转阴患者宫颈组织中的ALPK1表达升高。推测：ADP-heptose与ALPK1结合，维持阴道菌群稳态，是加味二妙颗粒清除HPV的机制所在。HPV不能离开人体细胞存活，故本项目构建ADP-heptose-HaCat-PsV细胞模型，进一步探索ADP-heptose与HR-HPV感染的相关性；采集患者阴道拭子及宫颈脱落细胞，从分子生物学和免疫组化两个方面，阐明ADP-heptose与ALPK1结合是清除HPV的机制，为研发清除HPV的新药提供基础研究依据。

Squamous intraepithelial lesion (SIL) of cervical is closely related to invasive cervical cancer, and persistent high-risk human papillomavirus (HR-HPV) infection is an important cause of SIL. The imbalance of the vaginal microecology is required for the HR-HPV infection. There are no specific drugs for HPV elimination. Previous studies and literatures have shown that the Modified Ermiao Granules can effectively eliminate HPV, but the therapeutic mechanism has not been fully understood. Adenosine heptose diphosphate (ADP- Heptose), an important metabolite of the vaginal flora, which is presented differently in the cervical and vaginal secretion samples from HPV-negative and positive subjects. Meanwhile，ALPK1 was significantly increased in cervical tissues of HPV positive patients who turned negative. Therefore, we speculate that the Modified Ermiao Granules mechanics may clear HPV by maintaining the homeostasis of the vaginal flora through the combination of ADP-heptose and ALPK1. Due to that HPV cannot survive in vitro, this project builds an ADP-heptose-HaCat-PsV cell model to further study the correlation between ADP-heptose and HR-HPV infection. In addition, we utilize the vaginal swabs and cervical shed cells that collected from women who were involved in this project, to expound the combination of ADP-heptose and ALPK1 as a mechanism of HPV clearance from two aspects of molecular biology and immunohistochemistry. Ultimately, this project provides a research basis for the development of new and specific drugs that may have extremely high clearance rate of HPV in the future.