寡肽VLPALPQ对小鼠妊娠耐受的免疫调节作用

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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 observe the effect of Val-Leu-Pro-Ala-Leu-Pro-Gln (VL-PALPQ) Mouse abortion model pregnancy outcome, and through the analysis of lymphocyte subsets and intracellular IL-12 levels of immune regulation mechanism. Methods The dsRNA was injected into BALB / c × c57BL / 6 mice for 7.5 days to establish an induced abortion model. VLPALPQ was intraperitoneally injected during pregnancy for several times, and the control group was replaced by PBS. The embryo resorption rates at 9 d and 13 d of pregnancy were calculated respectively. The changes of IL-12 in various lymphocyte subsets and CD45 + cells in peripheral blood and placenta were analyzed by 4-color flow cytometry. Results Compared with the induced abortion group, the embryo absorption rate of VLPALPQ treatment group decreased significantly (P <0.05) on the 9th day and decreased significantly on the 13th day of pregnancy (P <0.01). Correspondingly, the expression of IL-12 in CD45 + cells in peripheral blood and placenta decreased significantly (P <0.01), and the percentage of activated lymphocytes in placenta also decreased significantly. In addition, the co-stimulatory factor CD86 expression was also significantly reduced on the 13th day of pregnancy. Conclusion VLPALPQ could reduce the expression of IL-12, inhibit the enhancement of TH1-type immune response induced by dsRNA, and reduce the abortion rate of mice by inhibiting the activity of immune cells.
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