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背景:慢加急性肝衰竭(ACLF)是我国常见的肝衰竭类型,目前尚缺乏能有效模拟ACLF免疫状态动态转变的动物模型。目的:通过刀豆球蛋白A(ConA)重复给药,建立模拟ACLF免疫状态动态转变的动物模型。方法:小鼠随机分为对照组和ConA重复给药组,ConA重复给药组小鼠给予球后内眦静脉丛注射ConA 15 mg/kg,每隔48 h一次,共5次,对照组给予等体积0.9%NaCl溶液。CBA法检测外周血IL-6、IL-10、IL-12、TNF-α、IFN-γ、MCP-1水平,并测定IL-10/TNF-α比值;流式细胞术检测外周血中单核细胞HLA-DR表达、CD4~+T细胞数量及其比例以及PD-1表达。结果:随着给药次数增加,ConA重复给药组小鼠外周血细胞因子从促炎细胞因子为主转变成抗炎细胞因子为主。与对照组相比,ConA重复给药组外周血中单核细胞HLA-DR表达下降(P<0.05);CD4~+T细胞数量和比例下降(P<0.05),PD-1表达上调(P<0.05)。结论:本研究通过ConA重复刺激成功建立了模拟ACLF免疫状态从全身炎症反应综合征(SIRS)到代偿性抗炎反应综合征(CARS)动态转变的动物模型。
BACKGROUND: Slow-onset acute liver failure (ACLF) is a common type of liver failure in our country. Currently, there is a lack of animal models that can effectively simulate the dynamic changes of immune status in ACLF. OBJECTIVE: To establish an animal model to simulate the dynamic changes of immune status of ACLF by repeated administration of concanavalin A (ConA). Methods: The mice were randomly divided into control group and ConA repeated administration group. ConA repeated administration group received intranasal injection of ConA 15 mg / kg, once every 48 hours, control group An equal volume of 0.9% NaCl solution. The levels of IL-6, IL-10, IL-12, TNF-α, IFN-γ and MCP-1 in peripheral blood were detected by CBA method. The ratio of IL-10 to TNF- The expression of HLA-DR, the number of CD4 ~ + T cells and their proportion and the expression of PD-1 in nucleated cells. Results: With the increase of the number of administration, the peripheral blood cytokines in the repeated administration of ConA group changed from pro-inflammatory cytokines to anti-inflammatory cytokines. Compared with the control group, the expression of HLA-DR in peripheral blood mononuclear cells of ConA group decreased (P <0.05), the number and proportion of CD4 ~ + T cells decreased (P <0.05) and the expression of PD-1 <0.05). CONCLUSIONS: In this study, animal models of ACLF immune status simulation from systemic inflammatory response syndrome (SIRS) to compensatory anti-inflammatory response syndrome (CARS) were successfully established by repeated stimulation with ConA.