摘要:
Objective To study the role of T cells activation in Meprin-α-mediated formation of atherosclerosis and its mechanism.Methods Thirty 6 weeks old apoE/ mice were randomly divided into model group,L-MeplA group and control group (10 in each group).The animals were given PBS,L-MeplA virus,and control virus plasmid after they were fed with a high fat diet for 10 weeks.Their aortic atherosclerotic plaques were observed with HE staining,peripheral T cell subgroups were detected by flow cytometry,and inflammatory cytokine secretion was tested by ELISA.Results The size of atherosclerotic plaques was significantly larger,the number of CD3 and CD4 T cells was significantly greater,and the serum IL-6 and IFN-γ levels were significantly higher in L-MeplA group than in model group (41.3±6.8 pg/ml vs 20.2±4.1 pg/ml,30.3±4.2 pg/ml vs 11.3±2.1 pg/ml,P<0.05).No significant difference was found in the number of CD3 and CD4 T cells,serum IL-4,IL-5,IL-10 and TGF-β levels between model group and control group (P>0.05).Conclusion The role of Meprin-α in mediating atherosclerosis is related with immune dysfunction.Meprin-α accelerates inflammatory response by mediating the Th1 cells activation,thus leading to formation of atherosclerosis.%目的 探讨小鼠血浆中T细胞激活在Meprin-α介导动脉粥样硬化形成中的作用及其机制.方法 选择6周龄载脂蛋白E-/-小鼠30只,随机分为模型组、L-MeplA组和对照组,每组10只,高脂喂食,并于第10周末分别给予PBS、L-MeplA病毒和对照病毒质粒.HE染色检测小鼠主动脉粥样硬化斑块生成情况,流式细胞术检测小鼠外周血T细胞亚群比例,酶联免疫吸附法检测小鼠血浆炎性因子的分泌.结果 与模型组比较,L MeplA组动脉粥样硬化斑块面积和CD3、CD4 T细胞比例显著增高,白细胞介素(IL)-6、IFN-γ水平显著增高[(41.3±6.8)pg/ml vs(20.2±4.1)pg/ml,(30.3±4.2)pg/ml vs (11.3±2.1)pg/ml,P<0.05].而模型组与对照组动脉粥样硬化斑块面积,CD3、CD4 T细胞比例,IL-4、IL-5、IL-10和转化生长因子β比较,差异无统计学意义(P>0.05).结论 Meprin-α介导动脉粥样硬化形成的作用与免疫功能失调有关,Meprin-α可通过介导1型辅助性T细胞激活进而加速炎性反应,最终导致动脉粥样硬化形成.