| Objective:To explore effect of CSA on the Th17 cell and pregnant outcomes in abortion prone matings,And investigate the role and clinical significance of IL-17(interleukin-17,IL-17)in early spontaneous abortion.Methods:The normal pregancy model(group A)and the abortion-prone model(group B)were established.Group B were then randomized and divided into five groups named group BO?B1?B2?B3 and B4 respectively(group BO named as abortion-prone group,CSA-treated groups for group B1-B4).On the day 4 of pregnancy(implantation window),1,5,10,15 mg/kg Cyclosporin A(CSA)were injected intraperitoneally(i.p)to mice in group B1?B2?B3 and B4 respectively.On the day 14 of gestation,the pregnant females were sacrificed,and the blood,spleen,and embryo were collected.? The resorption rates was calculated.? The serum levels of IL-17,IL-6 and IL-23 were measured by enzyme linked immunosorbent assay(ELISA).? The percentage of splenic CD4+IL-17A+cell in CD4+cells were analysed by flow cytometric analysis.?The expression of RORyt mRNA in placenta were detected By Real-time PCR.ELISA was used to determine the serum level of IL-17 in threatened abortion patients,inevitable abortion patients,normal pregnant women,normal non-pregnant women,successful treatment group,and unsuccessful treatment group.Chemiluminesent immunoassay assay(CLIA)were used to determine the serum level of Progesterone in threatened abortion patients,inevitable abortion patients,normal pregnant women.Real-time PCR was used to determine the expression of IL-17 mRNA in uterine deciduas of inevitable abortion patients and normal pregnant group.Results:1.Compared with normal pregnancy group,the resorption rates was significantly higher(P=0.03),the serum levels of IL-17,IL-6 and IL-23 were all significant higher(P<0.05),was significantly higher(P<0.05),and RORyt mRNA expression was significantly increased in abortion-prone group(P<0.01).2.Compared with abortion-prone group,the resorption rates was lower(P<0.05 in B2 and B3),the serum levels of IL-17,IL-6 and IL-23 were lower to different extent,the proportion of splenic CD4+IL-17A+cell were lower to different extent(P<0.05 in B2 and B3),and RORyt mRNA expression was significantly lower in CSA-treated groups.3.There were no significant difference between normal pregnancy group and CSA-treated groups in the resorption rates,the serum levels of IL-17,IL-6 and IL-23,the proportion of splenic CD4+IL-17A+cell,and the expression of RORyt mRNA(P<0.05).4.The serum level of IL-17 was increased stepwise from normal pregnant group,normal non-pregnant women,threatened abortion to inevitable abortion patients(P<0.05).Compared with normal pregnant group,normal non-pregnant women,the serum level of IL-17 was significantly higher(P<0.05).Compared with threatened abortion group,the serum level of IL-17 was higher in inevitable abortion group(P>0.05).Compared with normal pregnant group and normal non-pregnant women,the serum level of IL-17 was higher in threatened abortion group(P>0.05).5.The mRNA of inevitable abortion patients in uterine deciduas was significantly higher than that in normal pregnant group(P<0.05).6.IL-17 in serum was low-degree correlated with in the deciduas between normal pregnancy and inevitable abortion(r=0.049?0.034,P<0.05).7.The serum level of IL-17 for latter treatment in successful treatment group of threatened group,was distinctively lower than before(P<0.05).While the level of IL-17 for latter treatment was increased than former in failed treatment group.8.The serum level of IL-17 was low-degree negatively correlated with progesterone value in pregnant women(r=-0.498?-0.362?-0.435,P<0.05).Conclusion:1.The abnormal increase in Th17 cell and its related cytokines were involved in the occurrence of abortion.2.Administration of CSA at day 4 of gestation could inhibit the differentiation and function of Th17 cell in abortion-prone model,and improve the pregnancy outcome.3.Our pilot research didn't show the dose-dependent effect of CSA on Th17 cell and the related cytokines,however.Above all,CSA may be an effective drug for pregnancy failure,but more studies are needed to explore the safe and effective dosage.4.IL-17 may get involved in a pro-inflammatory response in mediated-fetal interface and lead to the imbalance of maternal-fetal immune tolerance,and play a role in the occurrence and development of abortion.5.Serum IL-17 may be mainly derived from deciduas.6.Progesterone might inhibit TH17 cells to secrete IL-17 by progesterone receptor,which could maintain the stabilization of internal environment and the balance of maternal-fetal immune tolerance,and may benefit the maintenance of pregnancy. |
PDF Full Text Request