复发性流产患者外周血Th1、Th2细胞因子水平变化及维生素D的干预效果

Changes of Th1 and Th2 cytokine levels in peripheral blood of patients with recurrent spontaneous abortion and the intervention mechanism of vitamin D

目的观察复发性流产(recurrent spontaneous abortion,RSA)患者外周血中Th1/Th2细胞因子水平变化,并使用维生素D对患者进行干预治疗,观察维生素D对RSA的防治效果及其可能作用机制。方法选取2018年1月至2019年8月就诊处于备孕期且曾有RSA史女性患者200例为观察组,采集入选患者肘静脉血,使用FACS Calibur型流式细胞仪(美国BD公司生产)采用流式荧光法测定测定Th1/Th2型细胞因子水平,选取同期在本院孕检无RSA史的正常育龄备孕期女性100例为对照组进行对照分析。对比2组入选者外周血中白介素-2(interleukin-2,IL-2)、白介素-4(interleukin-4,IL-4)、白介素-6(interleukin-6,IL-6)、白介素-10(interleukin-10,IL-10)、肿瘤坏死因子(tumor necrosis factor-α,TNF-α)、γ-干扰素(interferon-γ,INF-γ)水平变化;并根据观察组治疗后随访是否正常妊娠进行分组,对比不同妊娠结局组间Th1/Th2细胞因子水平变化。结果观察组外周血中IL-2、TNF-α及INF-γ水平均明显低高对照组,IL-4、IL-6、IL-10水平则明显低于对照组,差异组间比较均有统计学意义(P<0.05)。观察组患者治疗后经随访正常妊娠分娩160例,再发RSA 40例,流产组外周血中IL-2、TNF-α及INF-γ水平均明显高于正常组,IL-4、IL-6、IL-10水平则明显低于正常组,组间比较差异均有统计学意义(P<0.05)。结论RSA患者存在外周血Th1/Th2的平衡向Th1偏移现象,Th1/Th2型细胞因子水平异常与RSA发病关系密切;维生素D可通调整RSA患者Th1/Th2平衡向Th2偏移,进而达到防治RSA再次发病的防治目的。

Objective To observe the changes in T-helper 1(Th1)/T-helper 2(Th2)cytokine levels in the peripheral blood of patients with recurrent spontaneous abortion(RSA),and to explore the outcome of vitamin D intervention to RSA and the underlying mechanism.Methods A total of 200 female patients with a history of RSA and prepared for pregnancy who were treated in our hospital between January 2018 and August 2019 were enrolled in the observation group.The cubital venous blood samples were collected to measure Th1/Th2 cytokine levels by flow cytometry using the FACS Calibur platform.A total of 100 childbearing women who were prepared for pregnancy without a history of RSA during the same period were enrolled in the control group.Interleukin-2(IL-2),interleukin-4(IL-4),interleukin-6(IL-6),interleukin-10(IL-10),tumor necrosis factor-α(TNF-α),and interferon-γ(INF-γ)in the peripheral blood were compared.According to the pregnancy or not during the follow-up period,Th1/Th2 cytokin levels in subjects with different pregnant outcomes were compared.Results IL-2,TNF-αand INF-γlevels in the peripheral blood in the observation group were significantly lower than those in the control group,while IL-4,IL-6,and IL-10 levels were significantly lower than those in the control group(P<0.05).After treatment,there were 160 cases of normal pregnancy and delivery,and 40 cases of recurrent RSA in the observation group,and significantly higher levels of IL-2,TNF-αand INF-γ,and lower levels of IL-4,IL-6 and IL-10 were detected in the abortion group compared with the normal group(P<0.05).Conclusion The Th1/Th2 balance in peripheral blood of RSA patients shifts to Th1.Abnormal levels of Th1/Th2 cytokines are closely related to the pathogenesis of RSA.Vitamin D can adjust the Th1/Th2 balance to Th2 shift in RSA patients to achieve the goals of preventing and treating the recurrence of RSA.