安子合剂对ACA阳性流产小鼠母胎界面JAK/STAT3信号通路的影响

Influences of Anzi Heji on JAK/STAT3 Signaling Pathway on the Maternal-Fetal Interface of Mice Suffering ACA Positive Abortion

目的观察安子合剂对抗心磷脂抗体(ACA)阳性小鼠母胎界面JAK/STAT3信号通路的影响。方法以人β2-GPⅠ为诱导剂建立ACA阳性小鼠模型,空白组给予生理盐水,模型组给予人β2-GPⅠ;各治疗组分别给予阿司匹林和高、低两种不同剂量安子合剂,于妊娠第15天处死,计算胚胎吸收率,采用ELISA方法检测外周血ACA;采用免疫组化方法检测胎盘、蜕膜组织JAK、GP130、p-STAT3,以Western blot方法检测STAT3、p-STAT3。结果安子合剂低、高剂量组、阿司匹林组小鼠的胚胎吸收率明显降低,小鼠血清ACA的滴度也显著降低(P<0.05),母胎界面的JAK、GP130、p-STAT3的表达均增高,其中胎盘的JAK、p-STAT3的表达与模型组比较具有显著差异(P<0.05),蜕膜GP130、p-STAT3的表达与模型组比较具有显著差异(P<0.05)。结论 ACA导致妊娠丢失的病理机制与母胎界面JAK/STAT3信号通路有关,安子合剂发挥治疗作用的机制可能是通过提高胎盘JAK的表达、增强蜕膜GP130的表达,促进胎盘及蜕膜STAT3的活化。

OBJECTIVE It is to observe the influences of Anzi Heji on the JAK/STAT3 signaling pathways on the maternal-fetal interface of anticardiolipin antibody（ACA）positive mice.METHODS Establish ACA positive mice model with humanβ2-GPⅠ as derivant,and administer normal saline to the blank group and humanβ2-GPⅠto the model group;administer aspirin and high and low dose Anzi Heji respectively to each therapy group,kill the mice at the 15 th day of their pregnancy,calculate the embryo resorption rate,and test the ACA of peripheral blood by means of ELISA;test the JAK,GP130 and p-STAT3 of placenta and decidual tissue with immunohistochemical method,and test STAT3 and p-STAT3 with western blot method.RESULTS The embryo resorption rate of the mice of low-and high-dose Anzi Heji groups and aspirin group was lowered obviously,so was the titer of ACA in the serum of mice（P〈0.05）,the expression of JAK,GP130 and p-STAT3 on the maternal-fetal interface was raised,and wherein,the expression of JAK,p-STAT3 of placenta had significant difference from that of model group（P〈0.05）,and the expression of GP130 and p-STAT3 of decidual tissue had significant difference from that of the model group（P〈0.05）.CONCLUSION The pathomechanism for ACA to induce pregnancy loss is related to the JAK/STAT3 signaling pathways on the maternal-fetal interface,and the mechanism for Anzi Heji to produce therapeutic effect is possibly to promote the activation of STAT3 of placenta and decidual tissue by enhancing the expression of JAK of placenta and strengthening the expression of GP130 of decidual tissue.