冠心病外周血白细胞介素7表达对免疫应答的影响及可能机制分析

目的探讨冠心病外周血白细胞介素7(IL-7)表达对免疫应答的影响及可能机制。方法选择冠心病患者82例,根据诊断分为稳定性心绞痛组22例,不稳定性心绞痛组39例,急性心肌梗死组21例;同期选取健康志愿者20例为正常对照组。ELISA法检测血清IL-7、高敏C反应蛋白(hs-CRP)、B型钠尿肽(BNP)水平;流式细胞术检测T细胞免疫球蛋白黏蛋白分子3(Tim-3)水平。分离外周血单核细胞,重组IL-7刺激12 h为刺激者,采用重组IL-7刺激为未刺激者。检测Tim-3水平;Western blot检测信号转导和转录激活因子5(STAT-5)、磷酸化STAT-5(p-STAT-5)、细胞因子信号转导负调控因子3(Socs-3)蛋白表达水平。结果急性心肌梗死组血清IL-7、hs-CRP水平明显高于正常对照组(P<0.01);稳定性心绞痛组和不稳定性心绞痛组血清IL-7、hs-CRP水平与正常对照组比较,差异无统计学意义(P>0.05)。稳定性心绞痛组、不稳定性心绞痛组、急性心肌梗死组血清BNP明显高于正常对照组(P<0.05)。急性心肌梗死组Tim-3 CD4T细胞、Tim-3 CD8T细胞明显高于稳定性心绞痛组、不稳定性心绞痛组、正常对照组(P<0.05)。正常对照组和急性心肌梗死组刺激者Tim-3 CD8T细胞均明显高于未刺激者(2.61±0.87)%vs(0.88±0.30)%、(4.80±1.53)%vs(2.15±0.69)%,P<0.05]。急性心肌梗死组刺激者和未刺激者Tim-3 CD4T细胞和Tim-3 CD8T细胞明显高于正常对照组(P<0.01)。刺激者p-STAT-5、Socs-3蛋白相对表达量明显高于未刺激者(P<0.05),两者STAT-5表达比较无显著差异(P>0.05)。结论急性心肌梗死患者外周血IL-7水平明显升高;IL-7可通过上调Tim-3表达,在冠心病发生、发展中发挥抑制炎性应答的作用。

Effect of IL-7 expression on immune response in CHD patients and its mechanism

Objective To study the effect of IL-7 expression on immune response in CHD patients and its mechanism.Methods Eighty-two CHD patients were divided into stable angina pectoris(SAP)group(n=22),unstable angina pectoris(UAP)group(n=39)and acute myocardial infarction(AMI)group(n=21)with 20 healthy volunteers served as a control group.Their serum levels of IL-7,hs-CRP and NT-proBNP were measured by ELISA and their T cell immunoglobulin mucin molecule 3(Tim-3)levels were measured by flow cytometry.The expression of Tim-3 was detected after the peripheral mononuclear cells were isolated and stimulated by recombinant IL-7 for 12 h.The expressions of STAT-5,p-STAT-5 and Socs-3 proteins were detected by Western blot.Results The serum IL-7 and hs-CRP levels were significantly higher in AMI group than in control group(P<0.01)while no significant difference was detected in serum IL-7 and hs-CRP levels between SAP group,UAP group and control group(P>0.05).The serum NT-proBNP level was significantly higher in AMI group,SAP group and UAP group than in control group(P<0.05).The expression levels of Tim-3 CD4T and Tim-3 CD8T were significantly higher in AMI group than in SAP group,UAP group and control group(P<0.05).The rate of Tim-3 CD8T IL-7 in control group and AMI group(2.61%±0.87%vs 0.88%±0.30%,4.80%±1.53%vs 2.15%±0.69%,P<0.05)while that of Tim-3 CD4T and Tim-3 CD8T stimulated or not stimulated by recombinant IL-7 was significantly higher in AMI group than in control group(P<0.01).The expression levels of p-STAT-5 and Socs-3 proteins stimulated by recombinant IL-7 were significantly higher than those not stimulated by recombinant IL-7 in AMI group and control group(P<0.05)while no significant difference was detected in expression level of STAT-5 between the two groups(P>0.05).Conclusion The serum IL-7 level increases significantly in AMI patients and IL-7 can inhibit the inflammatory response by upregulating the Tim-3 expression in CHD patients.