高迁移率蛋白1/Toll样受体4信号通路与下肢动脉硬化闭塞症介入治疗后复发的相关性分析

Correlation between high mobility protein 1/toll like receptor 4 signaling pathway and recurrence of arteriosclerosis obliterans after interventional therapy

目的研究高迁移率蛋白1/Toll样受体4信号通路(HMGB1/TLR4)与老年下肢动脉硬化闭塞症(ASO)介入治疗后复发风险的相关性。方法2020年1月~2021年1月间收治的行介入治疗的ASO病人84例,共96条病变血管,采用逆转录实时荧光定量PCR(qRT-PCR)法于术后1周检测病人外周血单个核细胞(PBMCs)内HMGB1及TLR4 mRNA表达水平,放射免疫法及免疫比浊法检测血清内皮素-1(ET-1)及高敏C反应蛋白(hs-CRP)水平。术后随访12个月,统计靶血管再狭窄情况,将血管再狭窄者纳为复发组,无狭窄者纳为对照组,比较两组外周血PBMCs内HMGB1、TLR4水平及血清hs-CRP及ET-1水平,分析以上指标与ASO介入术治疗病人血管再狭窄之间的关系。结果介入治疗后,84例病人96条病变血管均开通,随访12个月后经双下肢超声及CTA检查提示有16例病人共18条病变血管再狭窄。复发组病人外周血PBMCs内HMGB1及TLR4表达水平及血清ET-1及hs-CRP高于对照组,差异有统计学意义(P<0.05)。复发组病人外周血PBMCs的HMGB1及TLR4表达量与血清ET-1及hs-CRP水平均呈正相关(r=0.393,0.378,0.411,0.407,P<0.05)。结论HMGB1/TLR4信号通路可能通过激活炎症因子释放,促进血管损伤,参与ASO病人介入术后复发。

Objective To study the correlation of high mobility group box protein 1/toll-like receptor 4(HMGB1/TLR4)signaling pathway with the risk of recurrence after interventional therapy for lower extremity arteriosclerosis obliterans(ASO)in the elderly.〖WTHZ〗Methods A total of 84 patients(96 vessels)with ASO who underwent interventional treatment from January 2020 to January 2021 were enrolled.One week after operation,the levels of HMGB1 and TLR4 mRNA in peripheral blood mononuclear cells(PBMCs)were detected by Real-time Reverse Transcription-Polymerase Chain Reaction(qRT-PCR),and the levels of serum endothelin-1(ET-1)and high-sensitivity C-reactive protein(hs-CRP)were detected by radioimmunoassay and immunoturbidimetry.The patients were followed up for 12 months,and the restenosis of target vessels was counted.Patients were classified into recurrence group and control group according to the presence or absence of restenosis.The levels of HMGB1 and TLR4 mRNA in peripheral blood PBMCs and the levels of hs-CRP and ET-1 in serum were compared between groups,and the relationship between the above indexes and vascular restenosis in ASO patients after interventional therapy was discussed.Results Postoperative examination showed recanalization in 96 diseased vessels of 84 patients after interventional therapy.All patients completed a 12 months follow-up,and 16 patients(18 vessels)had restenosis(recurrence group)as indicated by ultrasound and CTA of both lower limbs.The levels of HMGB1 and TLR4 mRNA in peripheral blood PBMCs and the levels of hs-CRP and ET-1 in serum were remarkably elevated in recurrence group compared with control group,with statistical difference(all P<0.05).Correlation analysis denoted that HMGB1 and TLR4 mRNA expression in peripheral blood PBMCs of patients in recurrence group were positively correlated with serum ET-1 and hs-CRP levels(r=0.393,0.378,0.411,0.407,P<0.05).Conclusion The HMGB1/TLR4 signaling pathway may be involved in post-interventional recurrence in ASO patients by activating the release of inflammatory factors and promoting vascular injury.