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人类子宫内膜中的炎症小体:在评估“母体方面”的进一步研究。

Inflammosome in the human endometrium: further step in the evaluation of the "maternal side".

机构信息

Department of Obstetrics and Gynecology, Università Cattolica Del Sacro Cuore, A. Gemelli Universitary Hospital, Rome, Italy.

Department of Obstetrics and Gynecology, Università Cattolica Del Sacro Cuore, A. Gemelli Universitary Hospital, Rome, Italy; International Scientific Institute Paolo VI, ISI, Università Cattolica Del Sacro Cuore, A. Gemelli Universitary Hospital, Rome, Italy.

出版信息

Fertil Steril. 2016 Jan;105(1):111-8.e1-4. doi: 10.1016/j.fertnstert.2015.09.027. Epub 2015 Oct 30.

Abstract

OBJECTIVE

To investigate the expression of inflammosome components (NALP-3, associated speck-like protein containing a CARD [ASC]) and their activation (caspase-1, interleukin [IL]-1β, and IL-18 secretion) in the human endometrium from fertile and women with history of recurrent pregnancy loss (RPL).

DESIGN

Experimental study.

SETTING

University hospital.

PATIENT(S): Ten fertile women (control group [CTR]) and 30 women with RPL.

INTERVENTION(S): None.

MAIN OUTCOME MEASURE(S): Endometrial samples were collected by hysteroscopy during the putative window of implantation and evaluated for chronic endometrial inflammation by hystopathological analysis. Inflammosome expression was analysed by immunohystochemical staining (27 RPL and 10 CTR women). The expression of NALP-3 and ASC protein was quantified by Western blot (30 RPL and 10 CTR women). Caspase-1 activation and IL-1β and IL-18 secretion was quantified by ELISA (30 RPL and 10 CTR women).

RESULT(S): We observed a significantly increased expression of inflammasome NALP-3 and ASC protein, an increased activation of caspase-1, and increased levels of IL-1β and IL-18 in RPL endometrium compared with CTR.

CONCLUSION(S): Abnormal activation of endometrial innate immunity by means of inflammosome, stimulated by pathogen- or damage-associated molecular patterns, may represent an additional mechanism, currently not investigated, negatively interfering with endometrial receptivity. More studies are required [1] to identify the primary trigger of endometrial inflammosome activation and its clinical impact in the occurrence of RPL; and [2] to validate the inflammosome components as a novel family of endometrial biomarkers and promising therapeutic targets in RPL.

摘要

目的

研究炎症小体成分(NALP-3、含 CARD 的衔接蛋白[ASC])的表达及其在有反复妊娠丢失(RPL)病史的女性和生育期女性的子宫内膜中的激活(半胱天冬酶-1、白细胞介素[IL]-1β和 IL-18 分泌)。

设计

实验研究。

地点

大学医院。

患者(或参与者):10 名生育期女性(对照组[CTR])和 30 名有 RPL 病史的女性。

干预措施

无。

主要观察指标

通过宫腔镜在假定的着床窗口期采集子宫内膜样本,并通过组织病理学分析评估慢性子宫内膜炎症。通过免疫组织化学染色(27 名 RPL 和 10 名 CTR 女性)分析炎症小体表达。通过 Western blot 分析 NALP-3 和 ASC 蛋白的表达(30 名 RPL 和 10 名 CTR 女性)。通过 ELISA 定量测定半胱天冬酶-1的激活以及 IL-1β和 IL-18 的分泌(30 名 RPL 和 10 名 CTR 女性)。

结果

与 CTR 相比,RPL 子宫内膜中炎症小体 NALP-3 和 ASC 蛋白表达显著增加,半胱天冬酶-1激活增加,IL-1β和 IL-18 水平升高。

结论

病原体或损伤相关分子模式刺激的子宫内膜固有免疫的异常激活(通过炎症小体)可能代表一种尚未被研究的额外机制,该机制对子宫内膜容受性产生负面影响。需要更多的研究[1]来确定子宫内膜炎症小体激活的主要触发因素及其在 RPL 发生中的临床影响;[2]验证炎症小体成分作为 RPL 的一种新型子宫内膜生物标志物家族和有前途的治疗靶点。

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