地屈孕酮对不明原因复发性自然流产患者外周血辅助T细胞的影响

目的探讨地屈孕酮补充治疗对不明原因复发性自然流产(URSA)患者外周血辅助性T细胞(Th)亚群Th1/Th2的影响。方法选取30例不明原因复发性自然流产患者为URSA组,另选取30例正常育龄妇女作为对照组,URSA组予以地屈孕酮治疗,对照组不采取任何治疗措施。两组均进行γ干扰素(IFN-γ)(Th1细胞因子)、白细胞介素-4(IL-4)(Th2细胞因子)的检测,观察URSA组妊娠情况,比较两组Th细胞因子变化情况、妊娠后不同时期Th1/Th2的变化,分析地屈孕酮对不同流产次数患者再次妊娠成功后Th细胞因子的影响。结果30例URSA患者妊娠28例,其中2例生化妊娠,3例妊娠40+d胚胎停育清宫,23例妊娠成功已转入产科定期产前检查。URSA组外周血Th1型细胞因子IFN-γ(26.37±3.13)pg/ml高于对照组的(17.01±3.22)pg/ml,差异有统计学意义(P<0.05)。两组Th2型细胞因子IL-4比较差异无统计学意义(P>0.05)。流产2次患者与流产>2次患者之间,IFN-γ活性出现升高趋势,Th1/Th2比值明显向Th1偏移。妊娠40 d及妊娠3个月,外周血Th1型细胞因子IFN-γ活性低于妊娠前,差异有统计学意义(P<0.05);与对照组比较差异无统计学意义(P>0.05);Th2型细胞因子IL-4活性高于妊娠前,差异有统计学意义(P<0.05)。Th1/Th2模式向后者偏移,Th1/Th2比值为4.37 vs 2.37。至孕3个月,偏移越趋于明显,5例妊娠失败患者外周血中,Th1型细胞因子IFN-γ及Th2型细胞因子IL-4与妊娠前比较,差异无统计学意义(P>0.05)。经地屈孕酮治疗后,流产2次的URSA患者Th1型细胞因子IFN-γ(16.03±5.11)pg/ml低于流产>2次的(21.48±1.83)pg/ml,差异有统计学意义(P<0.05);流产>2次的URSA患者呈现出更为明显的Th2偏移现象。结论地屈孕酮治疗可以使Th1/Th2平衡向Th2偏移,对免疫调节起重要作用,有利于妊娠成功。

The effect of dydrogesterone on peripheral blood T-helper in patients with unexplained recurrent spontaneous abortion

Objective To discuss the effect of dydrogesterone on peripheral blood T-helper(Th)in patients with unexplained recurrent spontaneous abortion(URSA).Methods There were 30 patients with unexplained recurrent spontaneous abortion selected as the URSA group,and 30 women of normal childbearing age as the control group.The URSA group was treated with dydrogesterone,and the control group did not take any treatment measures.Both groups were tested for interferon-gamma(IFN-γ)(Th1 cytokine)and interleukin 4(IL-4)(Th2 cytokine).The pregnancy situation in the URSA group was observed.The changes of Th cytokines,the changes of Th1/Th2 in different periods after pregnancy was compared,and the effect of dydrogesterone on Th cytokines in patients with different times of miscarriage was analyzed.Results There were 28 pregnancies in 30 URSA patients,including 2 biochemical pregnancies,3 pregnancies with 40+d of gestation plus embryo withdrawal and curettage,and 23 pregnancies were successful and transferred to obstetrics for regular prenatal examination.The IFN-γof peripheral blood Th1 type cytokine(26.37±3.13)pg/ml of the URSA group was higher than(17.01±3.22)pg/ml of the control group,and the difference was statistically significant(P<0.05).There was no statistically significant difference in Th2 cytokine IL-4 between the two groups(P>0.05).For patients with 2 miscarriages and patients with>2 miscarriages,the activity of IFN-γshowed an increasing trend,and the ratio of Th1/Th2 significantly shifted to Th1.On the 40 th d and the third month of pregnancy,the IFN-γactivity of peripheral blood Th1 type cytokine was lower than before pregnancy,the difference was statistically significant(P<0.05);there was no statistically significant difference compared with the control group(P>0.05).The IL-4 activity of Th2 type cytokine was higher than that before pregnancy,the difference was statistically significant(P<0.05).The Th1/Th2 pattern shifts to the latter,and the Th1/Th2 ratio was 4.37 vs 2.37.By the third month of pregnancy,the deviation became more obvious.In the peripheral blood of 5 patients with pregnancy failure,there was no statistically significant difference in Th1 type cytokine IFN-γand Th2 type cytokine IL-4 compared with those before pregnancy(P>0.05).After treatment with dydrogesterone,the IFN-γ(16.03±5.11)pg/ml of Th1 type cytokine in URSA patients with 2 miscarriages was lower than(21.48±1.83)pg/ml of patients with>2 miscarriages,and the difference was statistically significant(P<0.05);URSA patients with more than 2 miscarriages showed more obvious Th2 shift.Conclusion Dydrogesterone treatment can shift the Th1/Th2 balance to Th2,which plays an important role in immune regulation and is conducive to successful pregnancy.