子痫前期小鼠动物模型的NK细胞和细胞因子的变化

The alteration of natural killer cells and cytokines in preeclampsia-like mice

目的:探讨磷脂酰丝氨酸(PS)/磷脂酰胆碱(PC)诱导的先兆子痫模型小鼠中自然杀伤(NK)细胞在外周血、脾脏及子宫的数量及其表面受体的变化,同时了解外周血中的细胞因子(TGF-β、TNF-α和IFN-γ)的水平。方法:用磷脂酰丝氨酸(PS)/磷脂酰胆碱(PC)诱导小鼠出现先兆子痫(PE)样症状,流式细胞仪检测自然杀伤(NK)细胞在外周血、脾脏及子宫的数量和表面受体,酶联免疫法检测外周血中TGF-β、TNF-α和IFN-γ。结果:我们建立的PE样小鼠模型是成功的;与对照组相比,gd17.5时PS/PC组外周血和脾脏中NK细胞数目增加。gd11.5时子宫中NK细胞数目突然增加,随后逐渐降低,且在gd14.5和gd17.5时PS/PC组比对照组NK细胞数目明显减少。PS/PC组脾脏中表面受体CD122表达显著降低,而CD244、CD94及NKG2D均显著增加;子宫中所有表面受体显著降低。在gd11.5、gd14.5及gd17.5时,与对照组相比,PS/PC组外周血中TGF-β的表达水平显著增加;而TNF-α和IFN-γ表达的水平大多不发生明显变化。结论:PE可能与母胎界面处NK细胞的数量及表面受体改变有关。外周血中TGF-β的增加可能抑制子宫处NKG2D等NK细胞表面受体的表达。关于TNF-α和IFN-γ在PE样小鼠模型中的作用还需进一步研究。

Objective：To investigate the differences of the number and phenotype of NK cells in the peripheral blood, spleen and uterus as well as cytokines levels in the peripheral blood in phosphatidylserine （PS）/phosphatidylchohne （PC） microvesieles-induced PE-hke model ICR mice. Methods： ICR mice PE-like model was induced by phosphatidylserine （PS） /phosphatidylcholine （PC）, the number and phenotype of NK cells in the peripheral blood, spleen and utems was analysed by FCM, and cytokines （TGF-β,TNF-α and IFN-γ） levels in the peripheral blood was measured by ELISA.Results： ICR mice PE model was established successful. Compared with the controls, the number of NK cells ware elevated in the peripheral blood and spleen on gestation day （gd） 17.5. The number of NK cells in the uterus showed a sud- den increase on gd 11.5 and then gradually reduced, while the mice injected with PS/PC showed a significant reduction of NK cell number in the uterus on gd14.5 and gd17.5. PS/PC treated mice got higher CD244, CD94 and NKG2D expression on the spleen NK cells, while CD122 expression was decreased. The low expression of all surface receptors was observed on uterus NK cells. Compared with controls, the mice injected with PS/PC had significantly increased TGF-β level in peripheral blood, but TNF-α and IFN-γ reminded unchanged in the most period. Conclusion： PE may be related to the alteration of the number of NK cells as well as the receptor expressions on themselves. The increased TGF-β in the peripberal blood may inhibit the expression of the receptors such as NKG2D on NK cells. It is necessary to tmderstand the role of TNF-α and IFN-γ in PE-like mice model.