Cyclosporine A Inhibits Th2 Cell Activation In The Treatment Of Antiphospholipid Antibody Related Abortion

Objective: To study the effect of cyclosporine A(CsA)on the pregnancy outcome of anti phospholipid antibody(APL)positive abortion model mice,and whether it can reduce the antibody formation by inhibiting the abnormal activation of Th2 cells,so as to provide a scientific basis for the application of CsA in the treatment of APL related abortion.Methods: The Female C57 mice were randomly divided into five groups:Blank control group,APL group(model group),aspirin group,High concentration CsA group,Low concentration CsA group,8 mice in each group.Except for the blank control group,the other groups were given humanβ2 glycoprotein I as immunogen to establish APL-positive abortion mouse model.From the first day of pregnancy,mice in aspirin group,High dose CsA group,Low dose CsA group were given drug gavage,while mice in blank control group and APL positive group(model group)were given equal volume distilled water gavage once a day for 14 consecutive days.After 14 days,pregnant rats were sacrificed,uterine tissues were collected,and peripheral blood was tested respectively:(1)Calculate the embryo absorption rate of eachgroup.(2)ELISA method is used to detect the concentration of IFN-γ,IL-10,IL-4,ACA and anti-β2I antibody.(3)The percentage of Th1 and Th2 cells in peripheral blood cell suspension samples was analyzed by flow cytometric analysis.Results:(1)The embryo absorption rate of APL group was significantly higher than that of other groups(P < 0.05).Compared with APL group,the embryo absorption rate of CsA group and aspirin group decreased the most significantly(P < 0.05),and there was no significant difference between the two groups(P > 0.05).(2)The levels of ACA and anti β 2gp1 in APL group were significantly higher than those in blank group(P < 0.05),and the concentrations of ACA and anti β 2gpi in low dose CsA group,high dose CsA group and aspirin group were significantly lower(P < 0.05).Among them,the high dose CsA group decreased the most significantly,and the ability of clearing antibody was significantly better than aspirin group and low dose CsA(P < 0.05).(3)The expression level of Th2 cells in APL group was significantly higher than that in blank control group(P < 0.05).The level of Th2 in CsA group was significantly lower than that in APL group(P < 0.05).The Th1 level of APL group decreased,but there was no significant difference between the groups.(4)Compared with the blank group,IL-4 and IL-10 in APL group increased significantly(P < 0.05),while IFN-γ decreased,suggesting that the balance was biased in Th2 direction.Compared with APL,the average concentrations of IL-4 and IL-10 decreased significantly(P < 0.05),but the level of Th2 cytokines decreased significantly in CsA group compared with aspirin group.Conclusion:(1)CsA can significantly reduce the embryo absorption rate of APL abortion model rats and clear the peripheral blood APL.(2)CsA may reduce APL related abortion by inhibiting Th2 bias.