趋化因子诱饵受体D6在心肌梗死后心肌重塑中的作用及机制研究

摘要

Objective: To investigate the level of atypical chemokine receptor D6 during acute myocardial infarction (AMI) and the possible mechanisms of D6 on myocardial remodeling after AMI. Methods:35 AMI patients were enrolled and divided into hCCL2high group(n=18) and hCCL2low group(n=17) according to serum chemokine hCCL2 detection 72 h after AMI. CD14 + + CD16- inflammatory monocytes were analyzed by flow cytometry. Q-PCR was used to detect the D6 mRNA in peripheral blood monocytes at 3 d. Cardiac function was measured by echocardiography at 3 weeks. 30 AMI male BLAB/C mice were allocated in to mCCL2high group(n=17) and mCCL2low group(n=13) based on the detection of serum CCL2. CD11b+ inflammatory monocytes were analyzed by flow cytometry. Immunofluorescence staining was used to mark D6 positive cells. Q-PCR was used to determine D6 mRNA in the infarct at 3 d. 3 weeks later, mice cardiac function was investigated by small animal ultrasound. Results:CD14 + +CD16 - inflammatory monocytes in hCCL2high group were significantly higher than that of hCCL2low group in AMI patients (P <0. 001). D6 mRNA in monocytes was significantly higher in hCCL2low group in comparison with hCCL2high group (P<0. 001). However, the correlation between D6 mRNA and LVEF%showed no significance (P=0. 16). CD11b+ monocytes was significantly higher in mCCL2high mice compared to mCCL2low group (P<0. 001). D6 mRNA expressed in the infarct was significantly higher in mCCL2low group in comparison with mCCL2high group ( P < 0. 001 ). Immunofluorescence showed that D6 expressed in CD11b+marcophages and CD31 + endothelial cells. D6 in infarct area of AMI mice was positively correlated with LVEF% at three weeks (P<0. 001). Conclusion: Atypical chemokine receptor D6 could express in the infarct after AMI, high level of D6 can restrain the infiltration of the inflammatory monocytes. Possible mechanisms might due to specific binding CCL2 in the infarct and thus reduce myocardial remodeling after myocardial infarction.%目的：：研究急性心肌梗死( AMI)后患者体内趋化因子诱饵受体D6的水平变化过程以及D6在心肌梗死后影响心肌重塑的可能机制。方法：将35例AMI患者根据心肌梗死后72 h血清趋化因子CCL2的检测水平分为hCCL2high组(n=18)和hCCL2low组(n=17),流式细胞术分析外周血中CD14++CD16-炎症单核细胞比例,Q-PCR测定外周血单核细胞趋化因子诱饵受体D6 mRNA的表达,3周后超声心动图测定心脏功能。将30只AMI雄性BLAB/C小白鼠根据血清CCL2的检测水平分为mCCL2 high组( n=17)和mCCL2 low组( n=13),流式细胞术分析小鼠外周血中CD11 b+单核细胞比例；梗死心肌冰冻切片后免疫荧光染色D6阳性细胞,Q-PCR测定心肌梗死后3 d时间梗死区D6 mRNA的表达。3周后通过小动物超声检测小鼠心脏功能。结果：hCCL2high组患者外周血中CD14++CD16-炎症单核细胞比例显著高于hCCL2low组(P<0.001),其单核细胞D6受体的表达明显低于hCCL2low组(P<0.001),但单核细胞D6的表达与患者LVEF%未见明显相关性(P=0.16)。急性心肌梗死小鼠mCCL2high组外周血中CD11b+单核细胞细胞比例显著高于mCCL2low组(P<0.001),梗死心肌组织D6 mRNA表达显著低于mCCL2low组(P<0.001),小鼠梗死心肌免疫荧光可见D6表达于CD11 b阳性单核细胞和CD31阳性内皮细胞。3周后小鼠心脏超声示LVEF%与梗死区D6的表达呈正相关(P=0.01)。结论：急性心肌梗死后梗死区组织可表达趋化因子诱饵受体D6,梗死区D6的高表达可抑制心肌梗死后的炎症浸润。梗死区趋化因子诱饵受体D6通过特异性结合CCL2减少心肌梗死后心肌局部的炎症浸润进而减轻心肌梗死后的心肌重塑。