粒-巨噬细胞集落刺激因子在流产患者血清中的浓度及在子宫蜕膜组织中的表达研究

摘要

目的 测定粒-巨噬细胞集落刺激因子(GM-CSF)在流产患者血清中的浓度及在子宫蜕膜组织中的表达量,探讨其意义并分析可能的影响因素.方法 前瞻性留取2012年5月至2014年10月间就诊的先兆流产、难免流产患者与同期正常妊娠妇女外周血及子宫蜕膜组织,采用酶联免疫吸附试验(ELISA)分别测定先兆流产(58例)、难免流产(40例)、正常妊娠妇女(50例)血清GM-CSF浓度,并采用实时PCR技术分别检测难免流产(16例)、正常妊娠者(23例)子宫蜕膜组织中GM-CSF mRNA的表达量.运用统计学方法比较各组间GM-CSF水平差异,分析血清GM-CSF浓度与蜕膜GM-CSF mRNA的表达量的相关性,并探讨GM-CSF水平与患者年龄、孕龄、血清β人绒毛膜促性腺激素(β-hCG)水平及孕酮水平的关系.结果 先兆流产组与正常妊娠组血清GM-CSF浓度分别为(497.8 ± 25.4) pg/ml、(543.1 ± 29.3)pg/ml,均显著高于难免流产组血清GM-CSF水平(186.7 ± 16.8)pg/ml(P <0.05).难免流产组子宫蜕膜组织中GM-CSF mRNA的表达相对值(1.952 ± 0.166)显著低于正常妊娠组(3.203 ± 0.257)(P <0.05).难免流产组和正常妊娠组的血清与蜕膜组织中GM-CSF水平均呈高度正相关(r =0.921、0.854,P <0.05).三组患者的血清GM-CSF水平均与其年龄因素无关,而与孕龄呈中度正相关(r =0.723、0.573、0.509,P <0.05),与血清β-hCG水平(r =0.417、0.381、0.453,P <0.05)及孕酮水平(r =0.359、0.302、0.467,P <0.05)低度正相关.结论 ①难免流产患者血清GM-CSF水平显著低于正常妊娠妇女,提示GM-CSF在妊娠维持中可能起保护作用,GM-CSF水平降低至一定水平将导致流产发生.②GM-CSF在先兆流产和难免流产患者体内水平有显著性差异,提示测定流产患者体内GM-CSF水平对于判断预后具有一定意义.③妊娠时的血清和蜕膜组织中的GM-CSF水平具有高度相关性,反映了血清GM-CSF主要来源于蜕膜组织.④GM-CSF在妊娠维持中的作用可能与hCG和孕酮作用有关.%Objective To determine the serum concentration of granulocyte-macrophage colony-stimulating factor(GM-CSF)in pa-tients with spontaneous abortion and its expression in decidual tissue,and to analysis its affecting factors. Methods Patients with threatened abor-tion,inevitable abortion and normal pregnancy from May 2012 to October 2014 diagnosed in Affiliated Hospital of North Sichuan Medical College were enrolled in our study. Serum granulocyte-macrophage colony-stimulating factor concentration by using enzyme-linked immunosorbent as-say(ELISA)were measured in 58 threatened abortions,in 40 inevitable abortions and in 50 normal pregnancies. Expressions of GM-CSF mRNA in decidual tissues were detected using real time PCR(real-time PCR)in 16 inevitable abortions and in 23 normal pregnancies. GM-CSF level differences between groups were compared,correlation analysis between the expression of serum concentration of GM-CSF and GM-CSF mRNA in decidual cells mRNA were determined,and to explore the association between age of patients,gestational age,beta -hCG level serum,proges-terone level and serum GM-CSF level. Results The concentration of serum GM-CSF in threatened abortion group and in normal pregnancy group were 497.8 ± 25.4 pg/ml,and 543.1 ± 29.3 pg/ml,respectively,which were significantly higher than that in inevitable abortion group (186.7 ± 16.8 pg/ml)(P <0.05). The expression relative values in decidual tissues of GM-CSF mRNA in patients with inevitable abortions were 1.952 ± 0.166,significantly lower than that in normal pregnancy group(3.203 ± 0.257)(P <0.05). The serum GM-CSF levels in in-evitable abortion group and normal pregnancy group in decidual tissues showed highly positive correlation(r =0.921,0.854,P <0.05). The serum GM-CSF levels in all three groups were associated with gestational age(r =0.723,0.573,0.509,P <0.05),with serum beta-human chorionic gonadotropin(beta-HCG)levels(r =0.417,0.381,0.453,P <0.05)and with progesterone(r =0.359,0.302,0.467,P<0.05). Conclusion Serum GM -CSF levels in patients with inevitable abortions were significantly lower than those in normal pregnant women,suggesting that serum GM-CSF may play a protective role in pregnancy maintenance,reduce to a certain level will lead to abortion. There was a significant difference in threatened abortion and inevitable abortion in patients with GM-CSF levels,suggesting that serum GM-CSF level may have a prediction role in prognosis of abortion. Serum GM-CSF may mainly come from decidua because of association between serum and decidual tissue. GM-CSF may be associated with hCG and progesterone in maintenance of pregnancy.