IL-6反式传导通路在血管内膜增生和VSMCs表型转化中的作用研究
发布时间：2019-01-05 18:38
【摘要】：目的:下肢动脉硬化闭塞症(peripheral arterial disease, PAD)患者腔内血管成形术(percutaneous transluminal angiography, PTA)后1年再狭窄(restenosis, RS)发生率高达20%～50%,血管平滑肌细胞(vascular smooth muscle cells, VSMCs)由收缩表型向合成表型的转化被认为是RS发生的关键始动步骤,而血管损伤后的“炎症反应学说”越来越受到重视,本研究拟以白介素-6(interleukin-6, IL-6)这一代表性炎症因子为研究对象,首选从整体水平检测PAD患者血清IL-6水平与腔内治疗术后RS发生的相关性,进而从组织器官水平探讨IL-6反式信号通路对于内膜增生和VSMCs表型转化的影响作用。方法：第一部分：IL-6对PAD患者支架成形术后再狭窄的预测作用研究：纳入2013年8月至2014年3月于长海医院血管外科住院行腔内治疗的TASCⅡ分级C/D级股胭动脉病变患者共68例,检测基础及腔内治疗术后24小时血清IL-6和hs-CRP(high sensitivity C reactive protein, hs-CRP)水平,收集临床资料和影像资料特征,随访观察术后6月RS的发生,进行多变量Logistic回归分析;第二部分：IL-6反式传导通路在内膜增生和表型转化中的作用研究：建立小鼠股动脉Cuff植入损伤模型,给予IL-6反式传导通路特异性拮抗剂sgp130Fc进行干预,形态学检测——主要检测新生内膜厚度、面积和新生内膜／中膜面积比值等；免疫组织化学检测——抗平滑肌a肌动蛋白(smooth muscle α-actin, SMA)抗体和抗Calponin抗体用于检测VSMCs表型转化情况,抗增殖细胞核抗原(proliferating cell nuclear antigen, PCNA)抗体用于检测VSMCs增殖情况。结果：研究纳入的68例患者腔内治疗术后血清IL-6和hs-CRP水平较术前基础水平均发生明显升高,15例(22%)在6月时发生支架内再狭窄,logistic回归分析显示腔内治疗前后患者血清IL-6水平及其相对增长水平[ΔIL-60 to 24 (rel%)]与再狭窄发生均具有显著相关性,患者腔内治疗术后血清hs-CRP水平与6月时RS发生亦具有显著相关性,而血清hs-CRP基础水平及其相对增长水平[Δhs-CRP 0 to 24 (rel%)]与RS发生不具有显著相关性。小鼠股动脉Cuff植入术后3周发生明显的内膜增生[新生内膜面积比较27.39±8.67 vs 9.65±3.49 (×104, μm2), P0.001],进行sgp130Fc干预后PCNA表达显著降低(P=0.009),α-SMA (P=0.001)及Calponin (P0.009)表达显著升高。同时,sgp130Fc不影响体重变化和肝功能。结论：下肢动脉腔内治疗造成的血管损伤会诱发机体全身的炎症反应,腔内治疗前后患者血清IL-6水平及其相对增长水平[AIL-60 to 24(rel%)]是支架成形术后近中期再狭窄发生的独立危险因素,sgp130Fc可以通过抑制血管平滑肌细胞由收缩表型向分泌表型的转化及其增殖,从而发挥抑制再狭窄发生的作用,而不会对机体产生不良影响。
[Abstract]:Objective: to investigate the incidence of restenosis (restenosis, RS) in patients with lower extremity arteriosclerosis obliterans (peripheral arterial disease, PAD) one year after endovascular angioplasty (percutaneous transluminal angiography, PTA). The incidence of restenosis (restenosis, RS) was as high as 20% 50%, and vascular smooth muscle cell (vascular smooth muscle cells, The transformation of VSMCs from contractile phenotype to synthetic phenotype is considered to be the key initiation step of RS, and the "inflammatory response theory" after vascular injury has been paid more and more attention. This study intends to use interleukin-6 (interleukin-6,). IL-6), a representative inflammatory factor, was the first choice to detect the correlation between serum IL-6 level and RS after intracavitary therapy in patients with PAD. The effects of IL-6 transduction pathway on intimal hyperplasia and VSMCs phenotypic transformation were investigated at the tissue and organ level. Methods: part 1: predictive effect of IL-6 on restenosis after stenting in patients with PAD: TASC 鈪，
本文编号：2402152
[Abstract]:Objective: to investigate the incidence of restenosis (restenosis, RS) in patients with lower extremity arteriosclerosis obliterans (peripheral arterial disease, PAD) one year after endovascular angioplasty (percutaneous transluminal angiography, PTA). The incidence of restenosis (restenosis, RS) was as high as 20% 50%, and vascular smooth muscle cell (vascular smooth muscle cells, The transformation of VSMCs from contractile phenotype to synthetic phenotype is considered to be the key initiation step of RS, and the "inflammatory response theory" after vascular injury has been paid more and more attention. This study intends to use interleukin-6 (interleukin-6,). IL-6), a representative inflammatory factor, was the first choice to detect the correlation between serum IL-6 level and RS after intracavitary therapy in patients with PAD. The effects of IL-6 transduction pathway on intimal hyperplasia and VSMCs phenotypic transformation were investigated at the tissue and organ level. Methods: part 1: predictive effect of IL-6 on restenosis after stenting in patients with PAD: TASC 鈪，
本文编号：2402152
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