CT灌注及DSA对Ilizarov外固定架骨搬移术治疗糖尿病足疗效评价及疗效机制的动物实验及临床研究

The clinical treatment of diabetic foot is tricky. Recently, our hospital takes the lead in treatment of ischemic diseases with bone removal in Ilizarov external fixator. The treatment has shown obvious curative effect, but the mechanism is unclear. In our previous research, we identified that the feet microcirculation status of postoperative patients markedly improved from their CT perfusion results. We design four groups of animal model for this study, including tibia removal in Ilizarov external fixation (the Ilizarov tension stress under the rule of drafting force type), plaster external fixation (Wolff's law under the unlimited power type) on diabetes and normal rabbit. Before surgery and 1 week, 2 weeks, 4 weeks, 8 weeks after surgery, all of them undergo a series of examination, including CT perfusion, blood rheology and clinical biochemical examination, respectively. At the eighth week after surgery, DSA and specimens histopathological examination as well as related analysis will be made. To compare the patients’s data with diabetic foot before and after surgery as a control study, we tend to explore the relationship between the bone biomechanics, microcirculation and the CT perfusion and DSA results, and to establish imaging quantitative evaluation indicators of diabetic foot small vessels regeneration and microcirculation reconstruction, so that we can provide basic theoretical basis of the mechanism and curative effect evaluation for external Ilizarov fixator bone removal of diabetic foot.

糖尿病足临床治疗十分棘手。近年来我院在国内率先应用Ilizarov外固定架骨搬移术治疗糖尿病足，取得明显疗效，但其机制尚不清楚。本课题组在前期实验中发现术后病人双足CT灌注显示微循环状态明显改善。本课题将制作糖尿病兔及正常兔胫骨外固定架骨搬移（Ilizarov 张力－应力法则下的牵伸力型）及石膏术（Wolff 定律下的无限制力型）的动物模型共四组，分别在术前及术后第1周、2周、4周、8周行CT灌注检查、血液流变学、临床生化检查，术后第8周行CT灌注检查并取标本行组织病理学检查，进行相关分析；同时对糖尿病足患者进行术前、术后对照研究，探索CT灌注与DSA间接反映的微循环与骨组织生物力学之间关系，建立糖尿病足小血管再生、微循环重建的影像学定量评价指标，为揭示糖尿病足Ilizarov外固定架骨搬移疗效机制及疗效评价提供基础理论依据。

糖尿病足（简称“糖足”），WHO定义为在糖尿病患者中，与下肢远端神经异常和不同程度周围血管病变相关的足部感染、溃疡和（或）深部组织的破坏。由于糖尿病足治疗十分棘手，近十几年来，国内部分学者在骨外固定技术上拓展，采用Ilizarov骨瓣牵拉滑动技术（即骨搬移）研究糖尿病足的治疗，目前发现骨搬移后肢体远端血供得到了改善，达到了良好的保肢效果，但有关外固定架骨搬移术前、术后微循环重建的研究报道甚少，其疗效机制也尚未完全可知，因此本课题拟以动物实验为基础，结合临床病例及医学影像探索其可能机制。本研究通过对胫骨外固定架骨搬移（Ilizarov张力-应力法则下的牵伸力型）术前、术后的糖尿病家兔及糖尿病足患者行CT灌注检查，运用临床、影像学、组织病理学探索、评估并验证缓慢持续牵伸力对肌肉、筋膜、血管和神经具有同步生长及受损组织微循环能自然重建的机制。.临床试验研究中，CT（computed tomography）灌注下糖尿病足搬移组术后8周BF（Blood flow）、BV（Blood volume）、rBV（Relative blood volume）、PMB（permeability）、rMTT（relative mean transit time）、血管显影-达峰时间差T（EP-ES）均大于术前，ST（skin temperature）高于术前，且均具有统计学意义；动物试验中，骨搬移术后6周足部CT灌注BV、BF值与对照组有统计学差异，另外HE染色足部微血管密度（MVD microvessel density）及血样检测血管内皮因子（VEGF vascular endothelial growth factor）在术前及术后第6周时存在显著性统计学差异。为揭示糖尿病足Iiizarov外固定架骨搬移治疗疗效机制提供了一种新的思路和有效的途径，CT灌注可以有效的反应微血管的再生与重建；BF、BV、PMB、rBV、rMTT、T（EP-ES）与ST是评估骨搬移术前和术后灌注差异的有效指标。