STEMI患者PCI治疗前外周血miR-1、miR-21表达水平与细胞因子、氧化应激及治疗后冠状动脉再狭窄的关系

Correlations of expressions of micro RNA-1 and micro RNA-21 in peripheral blood before PCI with cy⁃tokines,oxidative stress,coronary restenosis in patients with STEMI

目的研究ST段抬高型心肌梗死(ST-segment elevation myocardial infarction,STEMI)患者经皮冠状动脉介入(percutaneous coronary intervention,PCI)治疗前外周血微小RNA(micro RNA,miR)-1、miR-21表达水平与细胞因子、氧化应激及治疗后冠状动脉再狭窄的关系。方法选择2015年2月至2017年5月在乐山市人民医院进行急诊PCI治疗并在治疗后进行1年随访的STEMI患者110例,根据是否发生再狭窄分为发生再狭窄的A组(n=34)和未发生再狭窄的B组(n=86);另取同期体检的110名健康者作为对照组。PCI治疗前采用荧光定量聚合酶链反应(polymerase chain reaction,PCR)法测定miR-1、miR-21的表达水平,采用酶联免疫吸附法测定血管生成素-2(angiopoietin,Ang-2)、血管内皮生长因子(vascular endothelial growth factor,VEGF)、白细胞介素(interleukin,IL)-1、IL-8、高迁移率族蛋白B1(high mobility group protein B1,HMGB1)、8-羟基脱氧鸟苷酸(8-hydroxydeoxyguanosine,8-OhdG)的浓度,采用硫代巴比妥酸法测定丙二醛(malondialdehyde,MDA)的浓度,采用黄嘌呤氧化酶法测定谷胱甘肽过氧化物酶(glutathione peroxidase,GPX)、超氧化物歧化酶(superoxide dismutase,SOD)的浓度。结果高miR-1表达水平PCI治疗患者的再狭窄发生率明显低于低miR-1表达水平PCI治疗患者[18.33%(11/60)vs. 38.33%(23/60),χ2=5.910,P=0.015],而高miR-21表达水平PCI治疗患者的再狭窄发生率明显高于低miR-21表达水平PCI治疗患者[36.7%(22/60)vs. 20%(12/60),χ2=4.104,P=0.043],差异有统计学意义。A组和B组患者的miR-1表达水平及VEGF、GPX、SOD浓度明显低于对照组,miR-21表达水平及Ang-2、IL-1、IL-8、HMGB1、MDA、8-OhdG浓度明显高于对照组,且A组上述变化趋势较B组更为显著,差异有统计学意义(P<0.05)。miR-1与VEGF、GPX、SOD呈正相关,与Ang-2、IL-1、IL-8、HMGB1、MDA、8-OhdG呈负相关;miR-21与VEGF、GPX、SOD呈负相关,与Ang-2、IL-1、IL-8、HMGB1、MDA、8-OhdG呈正相关。结论 STEMI患者PCI治疗前miR-1表达减少及miR-21表达增多与治疗后再狭窄及细胞因子、氧化应激异常有关。

Objectives To investigate the correlations of expressions of micro RNA-1(miR-1)and micro RNA-21(miR-21)in peripheral blood before percutaneous coronary intervention(PCI)with cytokines,oxidative stress,coro⁃nary restenosis in patients with ST-segment elevation myocardial infarction(STEMI).Methods Totally 110 patients with STEMI who underwent emergency PCI treatment in People′s Hospital of Leshan between February 2015 and May 2017 were selected and followed up for 1 year after surgery.According to whether restenosis occurred,they were divid⁃ed into A group(n=34)with restenosis and B group(n=86)without restenosis.In addition,110 healthy subjects who underwent physical examination during the same period were selected as control group.The expressions of miR-1 and miR-21 in peripheral blood of patients with STEMI were detected by fluorescence quantitative polymerase chain reaction(PCR)before PCI.The concentrations of angiopoietin-2(Ang-2),vascular endothelial growth factor(VEGF),interleukin(IL)-1,IL-8,high mobility group protein B1(HMGB1),8-hydroxydeoxyguanosine(8-OHdG)were measured by enzyme linked immunosorbent assay.The concentration of malondialdehyde(MDA)was determined by thiobarbituric acid method.The concentrations of glutathione peroxidase(GPX)and superoxide dismutase(SOD)were determined by xanthine oxidase method.Results The incidence of restenosis in PCI patients with high expression of miR-1 was significantly lower than that in PCI patients with low expression of miR-1[18.33%(11/60)vs.38.33%(23/60),χ^(2)=5.910,P=0.015]while the incidence of restenosis in PCI patients with high expression of miR-21 was significantly higher than that in PCI patients with low expression of miR-21[36.7%(22/60)vs.20%(12/60),χ^(2)=4.104,P=0.043].Expression of miR-1 and concentrations of VEGF,GPX and SOD in A group and B group were significantly lower than those of control group while expression of miR-21 and concentrations of Ang-2,IL-1,IL-8,HMGB1,MDA and 8-OhdG were significantly higher than those of control group;and the above change trend of A group was more significant than that of B group.MiR-1 positively correlated with VEGF,GPX and SOD,and negatively correlated with Ang-2,IL-1,IL-8,HMGB1,MDA and 8-OhdG;miR-21 negatively correlated with VEGF,GPX and SOD,and positively correlated with Ang-2,IL-1,IL-8,HMGB1,MDA and 8-OhdG.Conclusions The decreasing expression of miR-1 and the increasing expression of miR-21 in peripheral blood of patients with STEMI before PCI relates to the occurrence of restenosis and the abnormal cytokine secretion and oxidative stress.