寡肽VLPALPQ对小鼠妊娠耐受的免疫调节作用

Immunomodulation of oligopeptide VLPALPQ on murine pregnancy tolerance

目的观察hCG来源的寡肽缬-亮-脯-丙-亮-脯-谷胺(Val-Leu-Pro-Ala-Leu-Pro-Gln,VL- PALPQ)对双链RNA(dsRNA)诱导建立的小鼠流产模型妊娠结局的影响,并通过对淋巴细胞亚群及细胞内IL-12水平的分析研究其免疫调节机制。方法在BALB/c×c57BL/6小鼠孕7.5 d注射dsRNA以建立诱发性流产模型,孕期多次腹腔注射VLPALPQ进行干预,对照组以PBS代替。分别计算孕9 d和13 d胚胎吸收率,并用4色流式细胞术分析外周血和胎盘中多种淋巴细胞亚群及CD45+细胞内IL-12的变化。结果VLPALPQ处理组孕9 d时胚胎吸收率较诱发性流产组有明显下降(P<0.05),孕13 d时下降更为显著(P<0.01)。与此相应,外周血和胎盘中CD45+细胞内IL-12的表达均显著下降(P< 0.01),胎盘中活化型淋巴细胞比率也显著下降。另外,孕13 d时共刺激因子CD86的表达也明显减少。结论VLPALPQ可通过抑制免疫细胞的活性,减弱IL-12的表达,阻断dsRNA所引起的TH1型免疫反应的增强,从而降低小鼠的流产率。

Objective To investigate the effect of hCG-derived oligopeptide VLPALPQ on the pregnancy outcome of double-stranded RNA （dsRNA）-induced murine abortion model, and to explore the possible mechanism by analyzing lymphocyte subsets and intraeellular IL-12 expression with flow cytometry. Methods Induced-abortion model was estabhshed by injection of dsRNA at day 7.5 of gestation. Multiple injections of VLPALPQ were intraperitoneally performed during pregnancy, while PBS-treated group was used as a control. Resorption rate of embryos were calculated on both days 9 and 13. Meanwhile, four-color flow cytometry was performed to analyze lymphocyte subsets and the intracellular expression of IL-12. Results The resorption rate was significantly decreased at both day 9 （ P 〈 0.05） and day 13 （ P 〈 0.01） in VLPAlPQ-treated group. Accordingly, the intracellular IL- 12^＋ percentage in CD45^＋ cells was significantly decreased in both peripheral blood and placenta, concomitant with the decrease of placental immunocompetent cell proportion. In addition, the expression of costimulating molecule CD86 was also inhibited. Conclusion VLPALPQ might inhibit the activation of immune cells and the expression of intracellular IL-12, block the bias towards TH 1 type response resulted by dsRNA induction, and subsequently improve pregnancy outcome.