Research progress of mechanism and application of exosomes in diabetic ulcer
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下肢外周动脉疾病(PAD)较为常见，患者可表现为间歇性跛行、非典型腿痛或流动性受损[1]。部分患者可发展为晚期疾病，导致严重肢体缺血(CLI), 需要紧急血运重建，并可能导致截肢等并发症。除了其肢体相关事件的影响, PAD也与心血管事件的发生有关[2]。近年来，下肢动脉粥样硬化病变的腔内治疗技术应用广泛，如支架置入、斑块旋切、球囊扩张术等，相比于传统的大隐静脉移植术、动脉斑块剥脱术，大多数患者更愿意接受腔内微创治疗，但术后的短期、长期疗效却欠佳。有研究[3]报道支架内再狭窄(ISR)发生率可达48.2%。患者术后生活质量因ISR受到严重的影响。据统计[4]膝上动脉支架术后的患者中，术后1年ISR发生率为30.0%。自药物涂层球囊(DCB)技术应用以来，其远期通畅率佳、安全性好等优点可以弥补支架置入的缺点[5-6]。药物涂层球囊是在球囊导管的表面涂布一层药物，通过导管将抗增殖药物送达病变血管壁，抑制内膜增生，减少再狭窄，而且无异物排斥[7]。DCB早期主要用于冠状动脉疾病的治疗，在下肢动脉病变病例中使用较少[8]。本研究对本科接受DCB治疗患者早期疗效进行观察并随访，现将结果报告如下。
1. 资料与方法
1.1 一般资料
选取2016年10月—2017年10月接受DCB治疗的下肢动脉粥样硬化闭塞性疾病患者38例，其中男26例，女12例，平均年龄(65.76±11.17)岁; 高血压22例(57.89%), 糖尿病10例(26.31%), 高脂血症3例(7.89%), 脑梗死病史3例(7.89%), 冠心病8例(21.05%); 24例(68.42%)患者有吸烟史，9例(23.68%)有长期饮酒史; 38例患者中，3例为支架内再狭窄，11例累及髂动脉，累及膝下动脉5例，35例动脉狭窄或闭塞; 病变的长度平均为(150.21±72.76) mm; Fontaine分级Ⅱ期17例，Ⅲ期8例，Ⅳ期13例; Rutherford分级在4级以上表现为静息痛或足趾坏死15例, 4级22例, 3级1例。
1.2 手术方法
术前血管彩超、大血管CT血管造影(CTA)证实为下肢动脉粥样硬化病变。评估手术禁忌证并签署手术知情同意书和授权委托书。患者仰卧位，拟穿刺点常规消毒铺巾，以2%的利多卡因5 mL于腹股沟区拟穿刺点局部麻醉，选择合适的穿刺入路(对侧或同侧股动脉)。以Sedinger技术穿刺股动脉成功后，引入Cobra导管及导丝，使之配合对髂总动脉。用高压注射器进行造影，血管减影造影(DSA)下显示血管情况。置换翻山鞘，用导丝配合导管成功开通病变段血管后，沿导丝送入合适大小的普通球囊逐段反复扩张狭窄或闭塞段血管。造影显示管腔狭窄消失，造影剂顺利通过。沿导丝送入药涂球囊扩张2~3 min。如果在普通球囊扩张后显示狭窄仍有明显或者存在夹层(不影响血流动力学)，可采取支架补救术。如再次造影显示造影剂通过顺畅，术毕拔管，压迫器压迫止血，患者返回病房。
1.3 术后治疗
① 适当加强锻炼，注意控制血糖、血脂、血压，观察下肢皮温变化，注意下肢保暖。②阿司匹林肠溶片100 mg口服, 1次/d, 西洛他唑100 mg口服，2次/d。用药期间注意全身各处出血风险，及时调整药物剂量。有创操作前根据具体情况决定是否停药。③定期复查血常规、凝血、D-二聚体。④门诊定期复查下肢动脉CTA, 并咨询调整用药方案。⑤病情变化随诊。
1.4 随访结果
对38例患者于术后6个月、1年进行随访，门诊复查下肢动脉彩色多普勒超声、踝肱指数(ABI)、血管CTA。收集患者术后临床症状的变化、术后行走距离的变化(患者口述)，根据门诊大血管CTA、下肢动脉超声以及衍生收缩期峰值速度比 < 2.4判断病变血管是否通畅[9], 从而判断患者是否需要手术治疗。随访终点为发生与手术相关或其他原因导致的死亡、截肢、靶病变血管血栓形成等。
1.5 统计学分析
采用SPSS 22.0统计学软件进行分析。计量资料采用均数±标准差表示，采用独立样本t检验。计数资料以(%)表示, Rutherford分级采用箱式图比较。P < 0.05为差异有统计学意义。
2. 结果
本研究38例患者患肢血管均再通成功，术后随访期间均未发生与手术相关或其他原因导致的死亡、截肢、靶病变血栓形成等并发症，无需要手术再干预患者，随访率100.00%。术后6个月、1年的Ⅰ期通畅率为84.21%、73.68%。所有患者术后不同时点的ABI、行走距离、Rutherford分级均较术前显著改善(P < 0.05), 见表 1、图 1。
表 1 药物涂层球囊手术前后ABI、行走距离及Rutherford分级比较(x±s)指标 时点 水平 95% CI 踝肱指数 术前 0.44±0.12 0.39~0.47 术后第1天 0.86±0.15* 0.80~0.90 术后6个月 0.78±0.16* 0.74~0.84 术后1年 0.76±0.14* 0.71~0.80 行走距离/m 术前 108.55±11.68 71.85~145.26 术后6个月 789.47±104.10* 456.15~1 122.80 术后1年 668.68±68.57* 383.19~954.18 Rutherford分级 术前 4(4，5) — 术后第1天 3(2，3)* — 术后6个月 3(2，3)* — 术后1年 3(2，3)* — 患者术后第1天未能下地行走，未统计行走距离; 患者Rutherford分级以中位数表示。与术前比较, *P < 0.05。 3. 讨论
跨大西洋外周动脉疾病管理学会共识指南[10-12]中，血管腔内治疗被认定为一线治疗方案，较为常见的腔内治疗方案包括经皮血管成形术(PTA)、球囊扩张术、支架置入术和DCB等。在腔内技术日益成熟的今天，越来越多的人倾向于微创治疗，如支架的大量使用，特别是在股腘动脉病变的治疗中[13]。但因为支架置入术在胯关节病变治疗中常有断裂、血管损伤、阻碍侧支循环和引起局部炎症反应等事件发生，导致其应用受阻[14-16]。药物涂层球囊可以较好地解决这一问题。
Scheinert等[17]研究表明，与普通球囊成形术比较, DCB术后6、12、24个月通畅率均明显更高。本研究术后6个月、1年的通畅率为84.21%、73.68%。Bausback等[18]、Steiner等[19]研究显示，药涂术后6个月、1年的通畅率为87.00%、86.40%。与传统的手术方式相比，药涂球囊术具有安全、有效、药效持久、临床收益高等优点。药物紫杉醇可以长久性地抑制血管内膜增生，减少再狭窄的发生，同时也弥补了支架植入术的不足之处。对于多节段复杂性病变、支架内再狭窄病变等，DCB依然优势明显[20]。本研究为回顾性小样本研究，具有一定的局限性，包括非随机对照设计、单一的治疗方案、样本量较小且来自同一家医疗单位，需要进一步的深入研究。
综上所述，药涂球囊治疗下肢动脉狭窄闭塞病变可以获得较好的1年期随访结果，安全性方面与普通球囊类似。
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