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目的探讨激活蛋白-1(activator protein-1,AP-1)、巨噬细胞游走抑制因子(macrophage migration inhibitory factor,MIF)在人颈动脉粥样硬化斑块中的表达变化及作用机制。方法收集60例人颈动脉粥样硬化斑块标本(试验组,A组)和30例正常人肠系膜动脉标本(对照组,B组)。根据颈动脉超声检查结果将颈动脉粥样硬化斑块标本分为软斑组(A1,n=20)、混合斑块组(A2,n=20)、硬斑组(A3,n=20)。分别采用反转录-聚合酶链反应(RT-PCR)和Western blot法测定标本中AP-1亚单位c-Jun mRNA及蛋白表达水平,反映AP-1的表达水平。用酶联免疫法(ELISA)测定斑块组和对照组血清中MIF水平。结果 (1)人颈动脉粥样硬化斑块中c-Jun mRNA及蛋白较对照组表达上调(P<0.05),A1组较A3组表达显著升高(P<0.05),A2组与A1组和A3组分别比较无明显差异(P>0.05)。(2)斑块组比健康对照组血清中MIF的含量显著增高(P<0.05);A1组较A3组含量显著增高(P<0.05),A2组与A1组和A3组分别比较无明显差异(P>0.05)。(3)在人颈动脉粥样硬化斑块中,MIF浓度与c-Jun表达水平明显呈正相关(r=0.759,P<0.01)。结论 AP-1和MIF与人颈动脉粥样硬化斑块的形成及稳定性显著相关,其可能作为预测颈动脉粥样硬化斑块病变情况及斑块稳定性的一个指标。AP-1表达量与MIF浓度越高,斑块不稳定性越高。
Objective To investigate the expression and mechanism of activator protein-1 (AP-1) and macrophage migration inhibitory factor (MIF) in human carotid atherosclerotic plaque. Methods Sixty human carotid atherosclerotic plaque specimens (experimental group, group A) and 30 normal mesenteric artery specimens (control group, group B) were collected. Carotid atherosclerotic plaque specimens were divided into soft plaque group (A1, n = 20), mixed plaque group (A2, n = 20) and hard plaque group (A3, n = 20) . The expression of AP-1 subunit c-Jun mRNA and protein was detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot respectively. Serum levels of MIF in plaque group and control group were determined by enzyme-linked immunosorbent assay (ELISA). Results (1) The expression of c-Jun mRNA and protein in human carotid atherosclerotic plaque was increased compared with the control group (P <0.05), the expression of c-Jun mRNA in group A1 was significantly higher than that in group A3 (P <0.05) And A3 group were no significant difference (P> 0.05). (2) The content of MIF in plaque group was significantly higher than that in healthy control group (P <0.05); the content of A1 in group A3 was significantly higher than that in A3 group (P <0.05); there was no significant difference between A2 group and A1 group and A3 group (P> 0.05). (3) In human carotid atherosclerotic plaque, MIF concentration was positively correlated with c-Jun expression level (r = 0.759, P <0.01). Conclusions AP-1 and MIF are significantly associated with the formation and stability of human carotid atherosclerotic plaques, which may be used as an index to predict the carotid atherosclerotic plaque lesions and plaque stability. The higher the AP-1 expression and MIF concentration, the higher the plaque instability.