李美, 楼姣英. 清毒栓对高危型HR-HPV持续感染的疗效和机制研究. 2024. biomedRxiv.202412.00028
清毒栓对高危型HR-HPV持续感染的疗效和机制研究
通讯作者: 楼姣英, doctorlou@126.com
DOI:10.12201/bmr.202412.00028
To study the efficacy and mechanism of Qingdu suppository in the treatment of high risk human papillomavirus (HR-HPV) persistent infection
Corresponding author: Lou Jiaoying, doctorlou@126.com
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摘要:目的:从阴道微生态和局部黏膜免疫角度探讨外用中药清毒栓治疗宫颈高危型人乳头瘤病毒(High-risk human papillomavirus,HR-HPV)持续感染的作用机制。方法:本研究共收集2022年4月至2023年12月在北京中医药大学妇科及妇科内分泌门诊就诊患者90例,分为三组,其中HPV阴性组30例(对照组),HR-HPV持续感染组30例(随访组),清毒栓治疗组30例(治疗组)。治疗组于用药后第4个月月经干净后第3-7天内行多重聚合酶链反应(PCR)HPV检测及液基薄层细胞学技术(TCT)检测,并于入组时及用药结束月经干净后取阴道微生态拭子及阴道灌洗液,随访组和对照组于体检时采集。酶联免疫吸附(Enzyme linked immunosorbent assay,ELISA)法检测各组患者阴道灌洗液中分泌型lgA(secreted lgA,slgA)、前列腺素E2(prostaglandin E2, PGE2)、特异性免疫球蛋白E (immunoglobulin-E,lgE)、白细胞介素-4(interleukin-4, IL-4)、IL-12和γ-干扰素(interferon-gamma, IFN-γ)水平水平。结果:随访组患者阴道菌群密集度、菌群多样性、Nugent评分、PH值与对照组之间存在显著差异(P<0.05),两组清洁度、优势菌、白细胞酯酶差异无统计学意义(P>0.05)。用药组患者阴道分泌物清洁度、菌群密集度、菌群多样性显著改善(P<0.05),优势菌、nugent评分、PH值和白细胞酯酶差异无统计学意义(P>0.05)。随访组患者阴道灌洗液中IFN-γ、IL-4、IL-12、IgE、PGE2水平显著高于对照组(P<0.01),sIGA显著低于对照组(P<0.01);用药后IFN-γ、IL-4、IL-12、IgE、PGE2表达水平显著降低,sIGA表达水平显著升高(P<0.01)。结论:阴道微生态及Th1/Th2失衡导致宫颈HR-HPV持续感染,外用中药清毒栓治疗可以调节阴道微生态,改善HR-HPV感染患者Th1/Th2平衡向Th2漂移的失衡状态,从而有利于HR-HPV转阴。
Abstract: Objective: To explore the mechanism of Qingdu suppository in the treatment of high-risk human papillomavirus (HR-HPV) persistent infection from the perspective of vaginal microecology and local mucosal immunity. Methods: from April 2022 to December 2023, 90 patients in the Department of gynecology and gynecological endocrinology clinic of Beijing University of traditional Chinese medicine were collected and divided into three groups, including 30 cases in HPV negative group (control group), 30 cases in HR-HPV persistent infection group (follow-up group), and 30 cases in Qingdu suppository treatment group (treatment group). The treatment group received multiple polymerase chain reaction (PCR) HPV detection and liquid based thin layer cytology (TCT) detection within 3-7 days after menstruation was cleaned at the fourth month after medication, and vaginal microecological swabs and vaginal lavage fluid were taken at the time of enrollment and after menstruation was cleaned at the end of medication. The follow-up group and the control group were collected at the time of physical examination. The levels of secretory LGA (slgA), prostaglandin E2 (PGE2), immunoglobulin-E (IGE), interleukin-4 (IL-4), IL-12 and interferon gamma (IFN-γ) in vaginal lavage fluid were detected by enzyme linked immunosorbent assay (ELISA). Results: there were significant differences in vaginal flora density, flora diversity, Nugent score and pH value between the follow-up group and the control group (P<0.05), but there were no significant differences in cleanliness, dominant bacteria and leukocyte esterase between the two groups(P>0.05). The cleanliness, bacterial density and bacterial diversity of vaginal secretions in the treatment group were significantly improved (P<0.05), but there were no significant differences in dominant bacteria, Nugent score, pH value and leukocyte esterase (P>0.05). The levels of IFN -γ, IL-4, IL-12, IgE and PGE2 in vaginal lavage fluid in the follow-up group were significantly higher than those in the control group (P<0.01), and SIgA was significantly lower than that in the control group (P<0.01); After treatment, the expression levels of IFN -γ, IL-4, IL-12, IgE and PGE2 were significantly decreased, while the expression level of SIgA was significantly increased (P<0.01).Conclusion:Vaginal microecology and Th1/Th2 imbalance lead to cervical HR-HPV persistent infection. External use of Qingdu suppository can regulate vaginal microecology, improve the imbalance of Th1/Th2 balance drift to Th2 in patients with HR-HPV infection, and is conducive to the negative conversion of HR-HPV.
Key words: High-risk HR-HPV infection persisted; Qingdu suppository; Vaginal microecology; Mucosal immunity; Th1/Th2提交时间:2025-01-16
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