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经宫颈乙醇灌注构建和优化小鼠子宫内膜损伤模型。

Construction and Optimization of an Endometrial Injury Model in Mice by Transcervical Ethanol Perfusion.

机构信息

The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453100, China.

Stem Cell and Biotherapy Technology Research Center, College of Life Science and Technology, Xinxiang Medical University, Xinxiang, 453003, China.

出版信息

Reprod Sci. 2021 Mar;28(3):693-702. doi: 10.1007/s43032-020-00296-2. Epub 2020 Sep 16.

Abstract

This study aimed to establish a stable animal model of intrauterine adhesion (IUA) using a minimally invasive method that recapitulates the clinicopathologic characteristics of IUA. Mice were randomly divided into groups based on the ethanol treatment time (the EtOH-10 s, EtOH-20 s, EtOH-40 s, EtOH-1 min, and sham operation groups), and after the cervix was relaxed with phloroglucinol, the uterine horn was perfused with 95% ethanol through the cervix to induce endometrial injury. Eight days after the procedure, routine biochemical assays were performed to assess liver and kidney function; HE and Masson staining were used to assess uterine morphology and fibrosis; and immunohistochemistry was performed to evaluate the expression of CD31 and F4/80 in the endometrium. Furthermore, the fertility of mice in the EtOH-40 s group and the sham operation group was compared. As expected, the ethanol treatment time was positively correlated with the degree of uterine damage and kidney dysfunction in mice. In particular, the endometria of mice in the EtOH-40 s group were significantly thinner than those of mice in the sham operation group and exhibited severe necrosis, glandular loss, incomplete epithelial and glandular epithelial cell structure, severe tissue fibrosis, an activated inflammatory response, and a significant decrease in the number of fetuses, consistent with the clinical characteristics of severe IUA. In conclusion, this study resulted in successful establishment, by a minimally invasive transcervical ethanol perfusion technique, of a mouse model of endometrial injury, which could support an in-depth study of IUA pathogenesis and further promote the development of IUA therapies.

摘要

本研究旨在建立一种微创方法,以复制 IUA 的临床病理特征,从而建立稳定的宫腔粘连(IUA)动物模型。根据乙醇处理时间,将小鼠随机分为各组(EtOH-10 s、EtOH-20 s、EtOH-40 s、EtOH-1 min 和假手术组),并用 phloroglucinol 松弛宫颈后,经宫颈向子宫角内灌注 95%乙醇,以诱导子宫内膜损伤。术后 8 天,进行常规生化检测评估肝肾功能;HE 和 Masson 染色评估子宫形态和纤维化;免疫组织化学评估子宫内膜 CD31 和 F4/80 的表达。此外,比较了 EtOH-40 s 组和假手术组小鼠的生育能力。正如预期的那样,乙醇处理时间与小鼠子宫损伤和肾功能障碍的严重程度呈正相关。特别是,EtOH-40 s 组小鼠的子宫内膜明显比假手术组小鼠的薄,且表现出严重的坏死、腺体丢失、不完全的上皮和腺体上皮细胞结构、严重的组织纤维化、活跃的炎症反应以及胎儿数量显著减少,与严重 IUA 的临床特征一致。总之,本研究通过微创经宫颈乙醇灌注技术成功建立了小鼠子宫内膜损伤模型,这有助于深入研究 IUA 的发病机制并进一步促进 IUA 治疗方法的发展。

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