LEASO患者血清miR-21、miR-126水平与HMGB1/TLR4信号通路活性和术后复发的关系

Relationships of serum miR-21 and miR-126 expression with activation of HMGB1/TLR4 signaling pathway and recurrence in patients with LEASO

目的 探讨股腘型下肢动脉硬化闭塞症(LEASO)患者血清微小核糖核酸(miR)-21、miR-126水平与高迁移率族蛋白B1(HMGB1)/Toll样受体4(TLR4)信号通路活性和术后复发的关系。方法 选取行介入手术的股腘型LEASO患者120例,根据术后是否复发将股腘型LEASO患者分为复发组和未复发组。RF-qPCR剂检测血清miR-21、miR-126表达和外周血单个核细胞HMGB1 mRNA、TLR4 mRNA表达。采用Pearson相关性分析法分析股腘型LEASO患者血清miR-21、miR-126与外周血单个核细胞HMGB1 mRNA、TLR4 mRNA表达的相关性。多因素Logistic回归分析股腘型LEASO患者介入术后复发的影响因素。结果 120例股腘型LEASO患者随访2年,术后复发率为34.17%。与未复发组比较,复发组血清miR-21和外周血单个核细胞HMGB1 mRNA、TLR4 mRNA表达升高,血清miR-126表达降低(P均<0.05)。Pearson相关性分析显示,股腘型LEASO患者血清miR-21与外周血单个核细胞HMGB1 mRNA、TLR4 mRNA表达呈正相关(r分别为0.660、0.649,P均<0.05),miR-126与外周血单个核细胞HMGB1 mRNA、TLR4 mRNA表达呈负相关(r分别为-0.632、-0.641,P均<0.05),外周血单个核细胞HMGB1mRNA与TLR4 mRNA表达呈正相关(r=0.742,P<0.05)。多因素Logistic回归分析显示,高血压、糖尿病和miR-21、HMGB1 mRNA、TLR4 mRNA升高为股腘型LEASO患者介入术后复发的独立危险因素,miR-126升高为独立保护因素(P均<0.05)。结论 股腘型LEASO患者血清miR-21高表达和miR-126低表达与HMGB1/TLR4信号通路激活有关,是股腘型LEASO患者术后复发的独立影响因素。

Objective To investigate the relationships between serum microribonucleic acid(microRNA)-21,miR-126 expression and the activation of high mobility group protein B1(HMGB1)/Toll-like receptor 4(TLR4) signaling pathway and recurrence in patients with femoral-popliteal type lower extremity arteriosclerosis obliterans(LEASO).Methods Totally 120 patients with femoral-popliteal type LEASO who underwent interventional operation were selected,and then they were divided into the recurrence group and non-recurrence group according to whether recurrence occurred or not.The expression of serum miR-21 and miR-126 and the expression of HMGB1 mRNA and TLR4 mRNA in peripheral blood mononuclear cells were detected by RT-qPCR.The correlation between serum miR-21,miR-126 and the expression of HMGB1 mRNA and TLR4 mRNA in peripheral blood mononuclear cells of patients with femoral-popliteal type LEASO were analyzed by Pearson correlation analysis.The influencing factors for recurrence after interventional therapy in patients with femoral-popliteal type LEASO were analyzed by multivariate Logistic regression analysis.Results All these patients were followed up for 2 years,and the recurrence rate was 34.17%.Compared with the non-recurrence group,the expression of serum miR-21,HMGB1 mRNA and TLR4 mRNA in peripheral blood mononuclear cells increased,and the expression of serum miR-126 decreased in the recurrence group(all P<0.05).Pearson correlation analysis showed that,serum miR-21 was positively correlated with the expression of HMGB1 mRNA and TLR4 mRNA in peripheral blood mononuclear cells(r=0.660 and 0.649,respectively;both P<0.05),miR-126 was negatively correlated with the expression of HMGB1 mRNA and TLR4 mRNA in peripheral blood mononuclear cells(r=-0.632 and-0.641,respectively;both P<0.05),and HMGB1 mRNA in peripheral blood mononuclear cells was positively correlated with TLR4 mRNA expression(r=0.742,P<0.05).Multivariate Logistic regression analysis showed that,hypertension,diabetes,and increased miR-21,HMGB1 mRNA,and TLR4 mRNA were independent risk factors for recurrence after interventional therapy in patients with femoral-popliteal type LEASO,and increased miR-126 was an independent protective factor(all P<0.05).Conclusion The high expression of serum miR-21 and the low expression of miR-126 in patients with femoral-popliteal type LEASO are related to the activation of HMGB1/TLR4 signaling pathway,which are independent influencing factors for recurrence after operation in patients with femoral-popliteal type LEASO.