外周血液狼疮抗凝物质比值及Ｔ细胞免疫球蛋白黏蛋白分子３水平与孕早期复发性流产的相关性研究

目的 探讨外周血液狼疮抗凝物质(lupus anticoagulant, LA)比值和T细胞免疫球蛋白黏蛋白分子3(T cell immunoglobulin mucin molecule 3,Tim-3)水平与孕早期复发性流产(recurrent spontaneous abortion,RSA)的相关性。方法 收集2017年5月～2018年5月期间在陕西省商洛市中心医院产科就诊的97例妊娠妇女的血液及临床资料进行回顾性分析。所有研究对象经多普勒超声检查均为宫内妊娠; 依据妊娠早期是否有流产或流产史分为正常妊娠组(32例)、流产史组(35例)及流产组(30例)。血浆LA比值采用改良蝰蛇毒磷酯时间法测定,血清Tim-3水平采用酶联免疫吸附法检测。血清β-人绒毛膜促性腺激素(Beta-human chorionic gonadotropin,β-HCG)及孕酮水平采用电化学发光法检测。子宫螺旋动脉血流阻力指数(RI)采用彩色多普勒超声分析仪检测。比较分析以上指标的变化与孕早期RSA的相关性。结果 血浆LA在正常妊娠组、流产史组和流产组中的比值分别为1.04±0.19,1.14±0.22和1.28±0.33; 而血清Tim-3在三组中的水平分别为352.21±120.28,553.17±129.53和779.35±162.33ng/L,与正常妊娠组比较,LA比值及Tim-3水平在流产史组和流产组中显著增高,其中流产组中两指标增高的趋势更显著。以上结果的比较差异均有统计学意义(F=117.07～162.20,均P=0.000)。血清β-HCG,孕酮及RI在正常妊娠组、流产史组和流产组中的结果分别为91 369.6±39 237.2,53 963.5±28 653.2和23 659.3±11 357.9mIU/ml; 78.02±3.19,67.53±2.37和23.10±1.28nmol/L; 1.73±0.46,2.16±0.53和2.79±0.72。流产史组和流产组中的β-HCG和孕酮水平显著低于正常妊娠组,而RI则显著高于正常妊娠组,其中流产组β-HCG和孕酮水平降低更显著,而RI则增高更显著。以上结果比较的差异均有统计学意义(F=109.32～128.26,均P=0.000)。在流产组和流产史组中,LA比值及Tim-3水平分别呈正相关性(r=0.813,0.839,P均<0.01)。在流产史组中,LA比值及Tim-3水平分别与β-HCG水平,孕酮水平及RI有相关性(r_LA=-0.767,-0.739,0.753; r_Tim-3=-0.782,-0.757,0.769,P<0.01)。在流产组中,LA比值及Tim-3水平分别与β-HCG水平、孕酮水平及RI有相关性(r_LA=-0.798,-0.759,0.787; r_Tim-3=-0.813,-0.775,0.793,P<0.01)。结论 检测孕早期外周血液LA比值及Tim-3水平可以预测RSA的发生,并为RSA的临床治疗提供依据。

Study on the Relationship between Ratio of Lupus Anticoagulant and Levels of T-cell Immunoglobulin-Mucin Molecule 3 in Peripheral Blood and Recurrent Abortion in Early Pregnancy

Objective To investigate the correlation between the ratio of lupus anticoagulant(LA)and levels of T cell immunoglobulin mucin molecule 3(Tim-3)in peripheral blood and recurrent abortion(RSA)in early pregnancy. Methods The data were collected from May 2017 to May 2018. The blood and clinical data of 97 pregnant women hospitalized in the obstetrics department of Shangluo Central Hospital of Shaanxi Province were retrospectively analyzed.All the subjects were diagnosed as early intrauterine pregnancy by ultrasonography.They were divided into normal pregnancy group(32 cases), abortion history group(35 cases)and abortion group(30 cases)according to whether abortion occurred or abortion history existed in the early pregnancy.LA ratio and Tim-3 levels were measured by modified phospholipid ester time method and enzyme-linked immunosorbent assay,the levels beta-human chorionic gonadotropin(beta-HCG)and progesterone were detected by electrochemiluminescence analysis, and uterine spiral artery blood flow parameter resistance index(RI)was detected by color Doppler ultrasonography. Results The ratio of plasma LA in normal pregnancy group, abortion history group and abortion group were 1.04±0.19,1.14±0.22 and 1.28±0.33 respectively, while the level of serum Tim-3 in three groups were 352.21±120.28,553.17±129.53 and 779.35±162.33ng/L respectively. Compared with normal pregnancy group, LA ratio and Tim-3 levels were significantly higher in abortion history group and abortion group. In the abortion group,the two indicators increased more significantly,and the differences between the above results were statistically significant(F=117.07～162.20,P=0.000).The results of serum β-HCG, progesterone and RI in normal pregnancy group, abortion history group and abortion group were 91 369.6±39 237.2,53 963.5±28 653.2 and 23 659.3±11 357.9mIU/mL; 78.02±3.19,67.53±2.37 and 23.10±1.28 nmol/L,1.73±0.46,2.16±0.53 and 2.79±0.72, respectively. The levels of HCG and progesterone significantly decreased whereas RI significantly increased in abortion history group and abortion group compared with those in normal pregnancy group,which in abortion group decreased or increased more significantly than those in normal pregnancy group.The differences between the above results were statistically significant(F=109.32～128.26,P=0.000).The correlation analysis showed that LA ratio and Tim-3 levels were positively correlated in the abortion group and the abortion history group(r=0.813, 0.839,P< 0.01). In the abortion history group, LA and Tim-3 levels were negatively correlated with serum levels of β-HCG and progesterone whereas positively correlated with RI(r_LA=-0.767,-0.739,0.753; r_Tim-3=-0.782,-0.757,0.769,P<0.01).In the abortion group, LA and Tim-3 showed a similar trend with serum levels of β-HCG and progesterone, and RI(r_LA=-0.798,-0.759,0.787; r=-0.813,-0.775,0.793,P<0.01).Conclusion Detection of LA ratio and Tim-3 levels in peripheral blood can predict the occurrence of RSA in early pregnancy and provide a basis for clinical treatment of recurrent abortion.