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自然流产与胎盘内系统性 C5a 升高和补体抑制蛋白 mRNA 减少有关。

Spontaneous abortion is associated with elevated systemic C5a and reduced mRNA of complement inhibitory proteins in placenta.

机构信息

Department of Obstetrics & Gynecology, University of Texas Medical Branch at Galveston, Galveston, Texas, USA.

出版信息

Clin Exp Immunol. 2014 Sep;177(3):743-9. doi: 10.1111/cei.12371.

Abstract

Spontaneous abortion in early pregnancy due to unknown reasons is a common problem. The excess complement activation and consequent placental inflammation and anti-angiogenic milieu is emerging as an important associated factor in many pregnancy-related complications. In the present study we sought to examine the expression of complement inhibitory proteins at the feto-maternal interface and levels of complement split products in the circulation to understand their role in spontaneous abortion. Consenting pregnant women who either underwent elective abortion due to non-clinical reasons (n = 13) or suffered miscarriage (n = 14) were recruited for the study. Systemic levels of complement factors C3a and C5a were measured by enzyme-linked immunosorbent assay (ELISA). Plasma C5 and C3 protein levels were examined by Western blot. Expressions of complement regulatory proteins such as CD46 and CD55 in the decidua were investigated by quantitative polymerase chain reaction (PCR) and Western blot. The median of plasma C3a level was 82·83 ng/ml and 66·17 ng/ml in elective and spontaneous abortion patients, respectively. Medians of plasma C5a levels in elective and spontaneous abortion patients were 0·96 ng/ml and 1·14 ng/ml, respectively. Only plasma C5a levels but not C3a levels showed significant elevation in spontaneous abortion patients compared to elective abortion patients. Further, there was a threefold decrease in the mRNA expressions of complement inhibitory proteins CD46 and CD55 in the decidua obtained from spontaneous abortion patients compared to that of elective abortion patients. These data suggested that dysregulated complement cascade may be associated with spontaneous abortion.

摘要

不明原因导致的早期妊娠自然流产是一种常见问题。过多的补体激活以及随之而来的胎盘炎症和抗血管生成环境,正成为许多与妊娠相关并发症的一个重要相关因素。在本研究中,我们试图研究胎-母界面补体抑制蛋白的表达和循环中补体裂解产物的水平,以了解它们在自然流产中的作用。因非临床原因(n=13)或自然流产(n=14)而接受选择性流产的孕妇同意参与本研究。通过酶联免疫吸附试验(ELISA)测量补体因子 C3a 和 C5a 的系统水平。通过 Western blot 检测血浆 C5 和 C3 蛋白水平。通过定量聚合酶链反应(PCR)和 Western blot 研究补体调节蛋白(如 CD46 和 CD55)在蜕膜中的表达。选择性流产和自然流产患者的血浆 C3a 水平中位数分别为 82.83ng/ml 和 66.17ng/ml。选择性流产和自然流产患者的血浆 C5a 水平中位数分别为 0.96ng/ml 和 1.14ng/ml。与选择性流产患者相比,只有自然流产患者的血浆 C5a 水平而非 C3a 水平显著升高。此外,与选择性流产患者相比,自然流产患者蜕膜中补体抑制蛋白 CD46 和 CD55 的 mRNA 表达减少了三倍。这些数据表明,补体级联失调可能与自然流产有关。

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