目的 探讨人绒毛膜促性腺激素(human chorionic gonadotropin,hCG)来源的寡肽丙-谷胺-甘-缬(Ala—Gln—Gly-Val,AQGV)是否具有抗poly I:C诱导的小鼠胚胎吸收的作用及其可能的免疫机制。方法 给予异基因妊娠的BALB/c小鼠腹腔注射多聚次黄苷酸-胞苷酸(poly I:C)建立胚胎吸收模型,注射磷酸盐缓冲液组作为对照,观察孕期多次注射AQGV对胚胎吸收率的影响,并采用流式细胞术检测孕9.5d和13.5d胎盘和外周血中免疫活性细胞,包括T细胞、NK细胞、NKT细胞、B细胞和巨噬细胞等的百分率,以及早期活化标志CD25、共刺激分子CD86和细胞内细胞因子IL-12水平。结果 孕9.5d时AQGV组胎盘中巨噬细胞和B细胞所占比率和CD45^+细胞内IL-12水平显著低于流产模型组;孕13.5d时除上述变化外,AQGV组胎盘中T细胞所占比率显著低于流产模型组;孕9.5d时AQGV组外周血CD45^+细胞内IL-12水平明显低于流产模型组;孕13.5d时外周血NK细胞、巨噬细胞、B细胞所占百分率和CD45^+细胞内IL-12水平明显低于流产模型组。与此相应,AQGV组孕9.5d和13.5d胚胎吸收率也显著下降。结论 AQGV可降低胎盘局部和外周血免疫活性细胞的构成比和抑制免疫反应向Th1型转化,从而抑制poly I:C诱导的小鼠胚胎吸收。
Objective To investigate whether hCG-derived oligopeptide Ala-Gln-Gly-Val (AQGV) is capable of inhibiting poly I: C-induced murine abortion and its potential mechanism. Methods The abortion-model was established by poly I: C injection to female BALB/c impregnated allogenetically, with the phosphate buffer treated mice as control group. Resorption rate of embryos was calculated after multiple injections of AQGV. Meanwhile, the percentage of placental and peripheral blood lymphocyte subsets were detected with flow cytometry at days 9.5 and 13.5 including the proportions of T cell, NK cell, NKT cell, B cell and macrophage, in addition to early-stage activation marker CD25, costimulating molecule CD86 and intracellular production of IL-12. Results The percentage of placental macrophage, B cell and intracellular IL-12^+ percentage in CD45^+ cell population at day 9.5 in AQGV-treated group was significantly lower than those of the induced-abortion group. In addition, the placental T cell proportion at day 13.5 in AQGV group was significantly lower than that of the induced-abortion group. In peripheral blood, the proportion of intracellular IL-12^+ cells in CD45^+ population at day 9.5 in AQGV group, and the proportions of NK cell, macrophage, B cell, as well as CD45^+ IL-12^+ cell at day 13. 5 in AQGV group were significantly lower than those of the induced-abortion group. Accordingly, the resorption rate of embryos in AQGV-treated group was significantly decreased than that of the induced-abortion group, both at days 9.5 and 13.5. Conclusions The administration of AQGV appears to down-regulate the proportion of immunocompetent cells, block Thl type bias, and subsequently inhibit poly I:C-induced abortion.