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阴道益生菌卷曲乳杆菌对宫腔粘连小鼠模型及临床的改善作用。

Improvement of vaginal probiotics Lactobacillus crispatus on intrauterine adhesion in mice model and in clinical practice.

机构信息

Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.

National Engineering Research Center for Bioengineering Drugs and The Technologies, Institute of Translational Medicine, Nanchang University, Nanchang, China.

出版信息

BMC Microbiol. 2023 Mar 22;23(1):78. doi: 10.1186/s12866-023-02823-y.

Abstract

BACKGROUND

Intrauterine adhesion (IUA) is a frequent acquired endometrial condition, for which there is no effective preventive or treatment. Previous studies have found that vaginal microbiota dysregulation is closely related to endometrial fibrosis and IUA. Therefore, we wondered whether restoration of vaginal microbiota by vaginal administration of L. crispatus could prevent endometrial fibrosis and ameliorate IUA.

RESULTS

First, we created a mechanically injured mouse model of IUA and restored the mice's vaginal microbiota by the addition of L. crispatus convolvulus. The observations suggested that intrauterine injections of L. crispatus significantly decreased the degree of uterine fibrosis, the levels of IL-1β and TNF-α in blood, and downregulated the TGF-β1/SMADs signaling pathway in IUA mice. A therapy with L. crispatus considerably raised the abundance of the helpful bacteria Lactobacillus and Oscillospira and restored the balance of the vaginal microbiota in IUA mice, according to high-throughput sequencing. Then we conducted a randomized controlled trial to compare the therapeutic effect of L. crispatus with estrogen after transcervical resection of adhesion (TCRA). And the results showed that vaginal probiotics had a better potential to prevent intrauterine adhesion than estrogen.

CONCLUSIONS

This study confirmed that L. crispatus could restore vaginal microbiota after intrauterine surgery, inhibit endometrial fibrosis, and finally play a preventive and therapeutic role in IUA. At the same time, it is a new exploration for the treatment of gynecological diseases with vaginal probiotics.

CLINICAL TRIAL REGISTRATION

http://www.chictr.org.cn/ , identifier (ChiCTR1900022522), registration time: 15/04/2019.

摘要

背景

宫腔粘连(IUA)是一种常见的获得性子宫内膜疾病,目前尚无有效的预防或治疗方法。先前的研究发现,阴道微生物群失调与子宫内膜纤维化和 IUA 密切相关。因此,我们想知道阴道内给予 L. crispatus 是否可以通过恢复阴道微生物群来预防子宫内膜纤维化并改善 IUA。

结果

首先,我们创建了机械性损伤的 IUA 小鼠模型,并通过添加卷曲乳杆菌来恢复小鼠的阴道微生物群。观察表明,宫腔内注射 L. crispatus 可显著降低子宫纤维化程度、血液中 IL-1β 和 TNF-α 的水平,并下调 IUA 小鼠的 TGF-β1/SMADs 信号通路。高通量测序结果显示,L. crispatus 治疗可显著增加有益菌乳杆菌和 Oscillospira 的丰度,并恢复 IUA 小鼠阴道微生物群的平衡。然后,我们进行了一项随机对照试验,比较了经宫颈粘连切除术后 L. crispatus 与雌激素的治疗效果。结果表明,阴道益生菌在预防宫腔粘连方面比雌激素更有潜力。

结论

本研究证实 L. crispatus 可以在宫腔内手术后恢复阴道微生物群,抑制子宫内膜纤维化,最终在 IUA 中发挥预防和治疗作用。同时,这是使用阴道益生菌治疗妇科疾病的新探索。

临床试验注册

http://www.chictr.org.cn/ ,标识符(ChiCTR1900022522),注册时间:2019 年 4 月 15 日。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8210/10032012/3165548a40da/12866_2023_2823_Fig1_HTML.jpg

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