摘要
目的观察原因不明复发性流产(URSA)患者蜕膜组织中miR-133a-3p、TGF-β_(1)、SAR1A表达及免疫细胞改变,探讨miR-133a-3p、TGF-β1、SAR1A对孕妇发生URSA的预测价值.方法2023年7-12月邯郸市第一医院诊治URSA患者67例为URSA组,早孕期自愿终止妊娠者48例为对照组,2组均行清宫术.取2组蜕膜组织,采用实时荧光定量PCR法检测miR-133a-3p、TGF-β1 mRNA、SAR1A mRNA相对表达量;采用流式细胞术检测NK细胞、巨噬细胞、Treg细胞、CD4+T细胞、CD8+T细胞百分比;采用Pearson相关法分析URSA患者蜕膜组织miR-133a-3p、TGF-β1 mRNA、SAR1A mRNA表达的相关性;绘制ROC曲线,评估miR-133a-3p、TGF-β1 mRNA、SAR1 A mRNA单独及联合预测URSA的价值.结果(1)URSA组蜕膜组织miR-133a-3p相对表达量(32.17±9.47)高于对照组(17.15±6.42)(t=9.527,P=0.001),TGF-β1 mRNA、SAR1A mRNA相对表达量(0.62±0.23、0.75±0.23)均低于对照组(1.10±0.10、1.35±0.26)(t=13.610、13.240,P均<0.001).(2)URSA组蜕膜组织NK细胞、巨噬细胞、Treg细胞百分比[(57.01±10.99)%、(7.09±2.26)%、(6.03±1.12)%]低于对照组[(66.68±13.69)%、(15.25±2.18)%、(11.81±4.35)%](t=4.192、19.360、10.420,P均<0.001),CD4+T细胞、CD8+T细胞百分比[(18.24±5.04)%、(9.89±2.49)%]均高于对照组(10.83±3.09)%、(6.61±1.66)%](t=9.041、7.950,P均<0.001).(3)miR-133a-3p相对表达量与TGF-β1 mRNA、SAR1A mRNA相对表达量均呈负相关(r=—0.817,P=0.001;r=—0.821,P=0.001),TGF-β1 mRNA相对表达量与SAR1A mRNA相对表达量呈正相关(r=0.789,P=0.001).(4)miR-133a-3p、TGF-β1 mRNA、SAR1A mRNA分别以24.565、0.971、0.807为最佳截断值,预测孕妇发生URSA的AUC分别为0.890(95%CI:0.846~0.954,P=0.002)、0.830(95%CI:0.756~0.905,P=0.001)、0.817(95%CI:0.741~0.892,P=0.001),灵敏度分别为87.5%、75.0%、97.9%,特异度分别为79.1%、82.1%、56.7%;三者联合预测孕妇发生URSA的AUC为0.922(95%CI:0.849~0.955,P=0.001),灵敏度为95.8%,特异度为73.1%;三者联合预测孕妇发生URSA的AUC大于单独预测(Z=—2.885~—2.582,P均<0.05).结论URSA病理进程中可能存在miR-133a-3p/TGF-β1/SAR1 A调控途径和免疫异常,miR-133a-3p表达上调及TGF-β1、SAR1A表达下调的孕妇发生URSA的风险增大,三者联合预测孕妇发生URSA的价值较高.
Objective To observe the expressions of miR-133a-3p,TGF-β1,and SAR1 A in decidual tissue and the changes of immune cells in patients with unexplained recurrent spontaneous abortion(URSA),and to explore the predictive value of miR-133a-3p,TGF-β1 and SAR1 A for URSA.Methods From July to December 2023,67 URSA patients diagnosed and treated in the First Hospital of Handan were selected as the URSA group,and 48 women who voluntarily terminated pregnancy in the first trimester were selected as the control group.Both groups underwent uterine curettage.Decidual tissues were collected from both groups.The relative expressions of miR-133a-3p,TGF-β1 mRNA and SAR1 A mRNA were detected using quantitative real-time PCR.The percentages of NK cells,macrophages,Treg cells,CD4+T cells,and CD8+T cells were measured by flow cytometry.Pearson correlation analysis was used to analyze the correlations of the expressions of miR-133a-3p,TGF-β1 mRNA and SAR1 A mRNA in decidual tissue of URSA patients.ROC curves were plotted to evaluate the predictive values of miR-133a-3p,TGF-β1 mRNA and SAR1 A mRNA alone or in combination for URSA.Results(1)The relative expression of miR-133a-3p in decidual tissue was higher in the URSA group(32.17±9.47)than that in the control group(17.15±6.42)(t=9.527,P<0.001),while the relative expressions of TGF-β1 mRNA and SAR1 A mRNA were lower in the URSA group(0.62±0.23,0.75±0.23)than those in the control group(1.10±0.10,1.35±0.26)(t=13.610,13.240;both P values<0.001).(2)The percentages of NK cells,macrophages,and Treg cells in decidual tissue were lower in the URSA group[(57.01±10.99)%,(7.09±2.26)%,(6.03±1.12)%]than those in the control group[(66.68±13.69)%,(15.25±2.18)%,(11.81±4.35)%](t=4.192,19.360,10.420;all P values<0.001),while the percentages of CD4+T cells and CD8+T cells were higher in the URSA group[(18.24±5.04)%,(9.89±2.49)%]than those in the control group[(10.83±3.09)%,(6.61±1.66)%](t=9.041,7.950;both P values<0.001).(3)The relative expression of miR-133a-3p was negatively correlated with the relative expressions of TGF-β1 mRNA and SAR1 A mRNA(r=—0.817,P=0.001;r=—0.821,P=0.001),while the relative expression of TGF-β1 mRNA was positively correlated with that of SAR1 A mRNA(r=0.789,P=0.001).(4)Using the optimal cut-off values of 24.565 for miR-133a-3p,0.971 for TGF-β1 mRNA,and 0.807 for SAR1 A mRNA,the AUCs for predicting URSA were 0.890(95%CI:0.846-0.954,P=0.002),0.830(95%CI:0.756-0.905,P=0.001),and 0.817(95%CI:0.741-0.892,P=0.001),with sensitivities of 87.5%,75.0%,and 97.9%,and specificities of 79.1%,82.1%,and 56.7%,respectively.The combined prediction of them three yielded an AUC of 0.922(95%CI:0.849-0.955,P=0.001),with a sensitivity of 95.8%and a specificity of 73.1%.The AUC of the combined prediction was greater than that of each alone(Z=—2.885 to—2.582,all P values<0.05).Conclusions The pathological process of URSA may involve the miR-133a-3p/TGF-β1/SAR1 A regulatory pathway and immune abnormalities.Upregulation of miR-133a-3p and downregulation of TGF-β1 and SAR1 A are associated with an increased risk of URSA.The combination of these three markers has a high predictive value for URSA.
作者
王旭
王晓静
赵志红
刘璐
李利敏
张秀俊
WANG Xu;WANG Xiaojing;ZHAO Zhihong;LIU Lu;LI Limin;ZHANG Xiujun(Department of Laboratory,the First Hospital of Handan,Handan,Hebei 056002,China;Department of Obstetrics and Gynecology,the First Hospital of Handan,Handan.Hebei 056002.China)
出处
《中华实用诊断与治疗杂志》
2025年第11期1000-1006,共7页
Journal of Chinese Practical Diagnosis and Therapy
基金
河北省卫生健康委医学科学研究课题计划项目(20240441)。
