【摘要】：目的:下肢動(dòng)脈硬化閉塞癥(peripheral arterial disease, PAD)患者腔內(nèi)血管成形術(shù)(percutaneous transluminal angiography, PTA)后1年再狹窄(restenosis, RS)發(fā)生率高達(dá)20%～50%,血管平滑肌細(xì)胞(vascular smooth muscle cells, VSMCs)由收縮表型向合成表型的轉(zhuǎn)化被認(rèn)為是RS發(fā)生的關(guān)鍵始動(dòng)步驟,而血管損傷后的“炎癥反應(yīng)學(xué)說(shuō)”越來(lái)越受到重視,本研究擬以白介素-6(interleukin-6, IL-6)這一代表性炎癥因子為研究對(duì)象,首選從整體水平檢測(cè)PAD患者血清IL-6水平與腔內(nèi)治療術(shù)后RS發(fā)生的相關(guān)性,進(jìn)而從組織器官水平探討IL-6反式信號(hào)通路對(duì)于內(nèi)膜增生和VSMCs表型轉(zhuǎn)化的影響作用。方法：第一部分：IL-6對(duì)PAD患者支架成形術(shù)后再狹窄的預(yù)測(cè)作用研究：納入2013年8月至2014年3月于長(zhǎng)海醫(yī)院血管外科住院行腔內(nèi)治療的TASCⅡ分級(jí)C/D級(jí)股胭動(dòng)脈病變患者共68例,檢測(cè)基礎(chǔ)及腔內(nèi)治療術(shù)后24小時(shí)血清IL-6和hs-CRP(high sensitivity C reactive protein, hs-CRP)水平,收集臨床資料和影像資料特征,隨訪觀察術(shù)后6月RS的發(fā)生,進(jìn)行多變量Logistic回歸分析;第二部分：IL-6反式傳導(dǎo)通路在內(nèi)膜增生和表型轉(zhuǎn)化中的作用研究：建立小鼠股動(dòng)脈Cuff植入損傷模型,給予IL-6反式傳導(dǎo)通路特異性拮抗劑sgp130Fc進(jìn)行干預(yù),形態(tài)學(xué)檢測(cè)——主要檢測(cè)新生內(nèi)膜厚度、面積和新生內(nèi)膜／中膜面積比值等；免疫組織化學(xué)檢測(cè)——抗平滑肌a肌動(dòng)蛋白(smooth muscle α-actin, SMA)抗體和抗Calponin抗體用于檢測(cè)VSMCs表型轉(zhuǎn)化情況,抗增殖細(xì)胞核抗原(proliferating cell nuclear antigen, PCNA)抗體用于檢測(cè)VSMCs增殖情況。結(jié)果：研究納入的68例患者腔內(nèi)治療術(shù)后血清IL-6和hs-CRP水平較術(shù)前基礎(chǔ)水平均發(fā)生明顯升高,15例(22%)在6月時(shí)發(fā)生支架內(nèi)再狹窄,logistic回歸分析顯示腔內(nèi)治療前后患者血清IL-6水平及其相對(duì)增長(zhǎng)水平[ΔIL-60 to 24 (rel%)]與再狹窄發(fā)生均具有顯著相關(guān)性,患者腔內(nèi)治療術(shù)后血清hs-CRP水平與6月時(shí)RS發(fā)生亦具有顯著相關(guān)性,而血清hs-CRP基礎(chǔ)水平及其相對(duì)增長(zhǎng)水平[Δhs-CRP 0 to 24 (rel%)]與RS發(fā)生不具有顯著相關(guān)性。小鼠股動(dòng)脈Cuff植入術(shù)后3周發(fā)生明顯的內(nèi)膜增生[新生內(nèi)膜面積比較27.39±8.67 vs 9.65±3.49 (×104, μm2), P0.001],進(jìn)行sgp130Fc干預(yù)后PCNA表達(dá)顯著降低(P=0.009),α-SMA (P=0.001)及Calponin (P0.009)表達(dá)顯著升高。同時(shí),sgp130Fc不影響體重變化和肝功能。結(jié)論：下肢動(dòng)脈腔內(nèi)治療造成的血管損傷會(huì)誘發(fā)機(jī)體全身的炎癥反應(yīng),腔內(nèi)治療前后患者血清IL-6水平及其相對(duì)增長(zhǎng)水平[AIL-60 to 24(rel%)]是支架成形術(shù)后近中期再狹窄發(fā)生的獨(dú)立危險(xiǎn)因素,sgp130Fc可以通過(guò)抑制血管平滑肌細(xì)胞由收縮表型向分泌表型的轉(zhuǎn)化及其增殖,從而發(fā)揮抑制再狹窄發(fā)生的作用,而不會(huì)對(duì)機(jī)體產(chǎn)生不良影響。
[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，

本文編號(hào)：2402152