实验性病毒性心肌炎小鼠中核因子κB、单核细胞趋化蛋白-1的表达及意义

Expression and significance of nuclear factor κB and monocyte chemoattractant protein-1 in mice with viral myocarditis

目的:探讨核因子κB(nuclearfactorkappaB,NF-κB)活化、单核细胞趋化蛋白-1(monocytechemoattractantprotein-1,MCP-1)表达在小鼠病毒性心肌炎(viralmyocarditis,VMC)中的作用。方法:Balb/c小鼠40只随机分为2组:柯萨奇病毒B3(thecoxsack-ievirusB3,CVB3)感染组和对照组。分别在实验第7,14和21天处死动物,免疫组化检测心肌组织中NF-κB活化和MCP-1表达,反转录-聚合酶链反应(RT-PCR)方法检测心肌组织中MCP-1mRNA的表达,双抗体夹心ELISA法检测血清MCP-1含量。结果:①感染组小鼠心肌组织中NF-κB活化、MCP-1表达均较对照组明显增强(P<0.01),第14天达高峰,阳性信号指数分别为(38.28±8.25)和(28.47±4.36),且与心肌病变呈正相关。②感染组小鼠MCP-1mRNA的表达量明显增加,且第14天的表达量(0.74±0.17)大于第7天(0.55±0.13)和21d(0.24±0.06)。③感染组小鼠MCP-1表达增加与NF-κB活化呈正相关(r=0.685,P<0.05)。④与对照组比较,感染组小鼠血清MCP-1含量明显增加(P<0.001),第14天达高峰(20.464±3.347),且与心肌组织中MCP-1的表达水平一致。结论:MCP-1能调节炎性细胞至受损心肌组织中,降低了心脏功能,可能在VMC发病机制中发挥了重要作用,且其表达至少部分通过NF-κB的活化来调控。

AIM:To make an exploratory discussion on the effect of the activation of nuclear factor kappaB(NF κB)and the expression of monocyte chemoattractant protein 1(MCP 1) on viral myocarditis(VMC) in mice.METHODS: Forty Balb/c mice were randomly divided into two groups: coxsackievirus B3(CVB3)infected group and control group. Animals were killed on the 7th, 14th and 21st days. The immunohistochemical method was performed to detect the activation of NF κB and the expression of MCP 1 in myocardial tissue. The expression of MCP 1 mRNA in myocardial tissue was detected with reverse transcriptase polymerase chain reaction(RT PCR). The content of serum MCP 1 was assayed with enzyme linked immunoadsordent assay(ELISA).RESULTS: ①The NF κB activation and MCP 1 expression in myocardial tissue were reinforced in the infected group compared with those in the control group(P< 0.01), and peaked at day 14, the positive signal indexes were 38.28±8.25 and (28.47±4.36 respectively. Furthermore,NF κB activation and MCP 1 expression correlated positively with myocardial lesion. ②The expression level of MCP 1mRNA in mice in the infected group was increased significantly. The level of MCP 1mRNA expressed on the 14th day(0.74±0.17) was higher than that on the 7th day (0.55±0.13) and the 21st day(0.24±0.06).③The increase of MCP 1 expression were positively correlated with NF κB activation in the infected group(r=0.685, P< 0.05). ④The contents of serum MCP 1 in mice in the infected group were significantly increased compared with that in the control group(P< 0.001), and peaked at day 14[(20.464±3.347)ng/L]. Furthermore, the content of serum MCP 1 were coincident with the expression of MCP 1 in the myocardium.CONCLUSION: MCP 1 can regulate the active cells to the tissue of injured myocardium, which decreases the function of heart, and MCP 1 may play an important role in the pathogenesis of VMC, and NF κB activation partly controls for MCP 1 expression.