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目的:观察选择性改变母胎界面趋化因子CXCL12、CCL2、RANTES及其受体CXCR4、CCR2、CCR5的表达对自然流产模型小鼠妊娠结局的影响,探讨免疫学改造在不明原因复发性流产(URSA)治疗中的可行性。方法:选择经典模型动物建立正常妊娠与URSA小鼠模型,正常妊娠小鼠为对照组(10例),URSA小鼠随机分为5组:未干预组(10例)、CXCL12干预组(10例)、CCR2拮抗剂干预组(10例)、CCR5拮抗剂干预组(10例)和CXCL12+CCR2拮抗剂+CCR5拮抗剂联合干预组(10例)。Western Blot方法检测各组小鼠绒毛和蜕膜组织中趋化因子及其受体CXCL12/CXCR4、CCL2/CCR2、RANTES/CCR5蛋白的表达;同时观察各组小鼠胚胎丢失的情况,计算胚胎丢失率。结果:1URSA小鼠未干预组绒毛和蜕膜组织中CXCL12/CXCR4蛋白的表达显著低于正常妊娠对照组,而CCL2/CCR2和RANTES/CCR5蛋白的表达均显著高于正常妊娠对照组,差异有统计学意义(P均<0.05)。URSA小鼠CXCL12干预组绒毛和蜕膜组织中CXCL12/CXCR4蛋白的表达显著高于未干预组(P<0.05);但仍低于正常妊娠对照组(P<0.05)。URSA小鼠CCR2拮抗剂干预组绒毛和蜕膜组织中CCL2/CCR2蛋白的表达显著低于未干预组(P<0.05),但仍高于正常妊娠对照组(P<0.05)。URSA小鼠CCR5拮抗剂干预组绒毛和蜕膜组织中RANTES/CCR5蛋白的表达显著低于未干预组(P<0.05),但仍高于正常妊娠对照组(P<0.05)。URSA小鼠CXCL12+CCR2拮抗剂+CCR5拮抗剂联合干预组绒毛和蜕膜组织中CXCL12/CXCR4蛋白的表达显著高于未干预组(P<0.05);但仍低于正常妊娠对照组(P<0.05);CCL2/CCR2和RANTES/CCR5蛋白的表达均显著低于未干预组(P<0.05),但仍高于正常妊娠对照组(P<0.05)。2URSA小鼠未干预组的胚胎吸收率显著高于正常妊娠对照组,差异有统计学意义(P<0.01)。URSA小鼠CXCL12干预组、CCR2拮抗剂干预组、CCR5拮抗剂干预组和CXCL12+CCR2拮抗剂+CCR5拮抗剂联合干预组的胚胎吸收率均低于未干预组(P均<0.05),其中联合干预组下降更为显著(P<0.05),但仍高于正常妊娠对照组(P<0.05)。结论:可以通过选择性诱导母胎界面CXCL12/CXCR4蛋白高表达、CCL2/CCR2和RANTES/CCR5蛋白低表达改善URSA小鼠妊娠结局。
OBJECTIVE: To observe the effect of selective alteration of the expression of CXCL12, CCL2, RANTES and its receptors CXCR4, CCR2 and CCR5 on the pregnancy outcome in spontaneous abortion mice and to explore the possible mechanisms of immunological alterations in unexplained recurrent spontaneous abortion ) The feasibility of treatment. Methods: The normal pregnant mice and URSA mouse model were established. The normal pregnant mice were control group (10 cases). URSA mice were randomly divided into 5 groups: untreated group (10 cases), CXCL12 intervention group (10 cases) ), CCR2 antagonist intervention group (10 cases), CCR5 antagonist intervention group (10 cases) and CXCL12 + CCR2 antagonist + CCR5 antagonist intervention group (10 cases). Western Blot method was used to detect the expression of CXCL12 / CXCR4, CCL2 / CCR2 and RANTES / CCR5 in villus and decidua of mice in each group. At the same time, the loss of embryos of mice in each group was observed and the loss of embryos rate. Results: The expression of CXCL12 / CXCR4 in villus and deciduas of 1URSA mice was significantly lower than that of normal pregnant controls, while the expressions of CCL2 / CCR2 and RANTES / CCR5 were significantly higher than that of normal pregnant controls Statistical significance (P <0.05). CXCL12 / CXCR4 expression in villus and decidua in URSA mice CXCL12 intervention group was significantly higher than that in non-intervention group (P <0.05), but still lower than that in normal pregnancy control group (P <0.05). The expression of CCL2 / CCR2 protein in the villus and deciduas of URSA mice treated with CCR2 antagonist was significantly lower than that of the untreated group (P <0.05), but still higher than that of the normal pregnancy control group (P <0.05). The expression of RANTES / CCR5 in villus and deciduas of URSA mice treated with CCR5 antagonist was significantly lower than that of the untreated group (P <0.05), but still higher than that of the normal pregnancy control group (P <0.05). The expression of CXCL12 / CXCR4 in villus and deciduas of URSA mice combined with CXCL12 + CCR2 antagonist + CCR5 antagonist was significantly higher than that of non-intervention group (P <0.05), but still lower than that of normal pregnancy control group (P < 0.05). The expressions of CCL2 / CCR2 and RANTES / CCR5 were significantly lower than those in the non-intervention group (P <0.05), but still higher than those in the normal pregnancy control group (P <0.05). The embryo absorptivity of 2URSA mice without intervention group was significantly higher than that of normal pregnancy control group (P <0.01). URSA mice CXCL12 intervention group, CCR2 antagonist intervention group, CCR5 antagonist intervention group and CXCL12 + CCR2 antagonist + CCR5 antagonist combined intervention group embryos absorption rate were lower than the non-intervention group (P <0.05), which combined The intervention group decreased more significantly (P <0.05), but still higher than the normal pregnancy control group (P <0.05). Conclusion: The high expression of CXCL12 / CXCR4 protein and the low expression of CCL2 / CCR2 and RANTES / CCR5 protein in maternal fetal interface can improve the pregnancy outcome of URSA mice.