多脏器功能不全综合征小鼠IL-12的表达及其在免疫失衡中的作用

CHANGE IN IL-12 EXPRESSION AND ITS ROLE IN IMMUNODISSONANCE IN MODS MICE

目的 探讨多脏器功能不全综合征 (MODS)小鼠在伤后不同时相IL 12水平的变化趋势及其与创伤后免疫失衡的关系。方法 选择 6～ 8周龄雄性C5 7BL/ 6小鼠 96只 ,随机分为正常组 ,伤后 3h、1、3、7和 12天组。腹腔注射酵母多糖复制MODS动物模型 ,用Powervision法行脾脏IL 12p40的免疫组织化学标记 ,采用ELISA法分别检测血清与脾脏组织匀浆上清中IL 12 p40和IL 12 p70的水平 ,流式细胞术检测外周血T细胞亚群。结果 在MODS病程早期和晚期的“两次打击”中 ,小鼠脾脏与血清中IL 12p40含量显著增高 ,IL 12p70相对减少 ,同时伴有外周血CD4/CD8比值下降。结论 MODS小鼠发生免疫抑制可能与免疫器官中抗原提呈细胞高表达IL 12p40有一定相关性。

Objective To determine the dynamic change in IL-12 in MODS mice at different post-trauma time points and its relationship with immunodissonance. Methods 96 male C57BL/6 mice, 6-8 weeks old, were randomly divided into normal control, 3h, 24h, 3d, 7d and 12d post-trauma groups. MODS model were replicated by injection of zymosan into the peritoneal cavity of the mice. Spleen and blood were sampled at different time points. Pathological changes of spleen were observed by light microscope. Immunohistochemistry marker of IL-12p40 in spleen was produced by Powervision method. The levels of IL-12p40 and IL-12p70 in serum and homogenate of spleen were determined by enzyme-link immuno-sorbent assay,and T lymphocyte subsets were analyzed by flow cytometry, respectively. Results Atrophy of the white pulps, proliferation of monocytes and dendritic cells, infiltration of neutrophilic granulocytes in the red pulps could be seen in 12d post trauma group. During the 'two hits' in early period (3-24h) and late period (12d) in MODS, the amount of IL-12p40 positive cells increased significantly in the spleen; the level of IL-12p40 increased, whereas the level of IL-12p70 decreased evidently, in serum and the homogenate of the spleen. In the early period, the amount of CD8 + T cells in peripheral blood increased, while the amount of CD4 + T cells reduced obviously in the late stage, thus CD4/CD8 ratio declined in both periods. Conclusions The results indicated that over expression of IL-12p40 by antigen presenting cells in immune organs was correlated with immunosuppression of MODS mice.