包含膜联蛋白V和库尼茨抑制剂结构域的新型损伤部位靶向融合蛋白可改善缺血再灌注损伤并促进缺血大鼠腹部皮瓣存活。
Novel Injury Site Targeted Fusion Protein Comprising Annexin V and Kunitz Inhibitor Domains Ameliorates Ischemia-Reperfusion Injury and Promotes Survival of Ischemic Rat Abdominal Skin Flaps.
作者信息
Shyu Victor Bong-Hang, Hsu Chung En, Wen Chih-Jen, Wun Tze-Chein, Tang Rui, Achilefu Samuel, Wei Fu-Chan, Cheng Hui-Yun
机构信息
From the *Center for Vascularized Composite Allotransplantation, †Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital; ‡School of Medicine, Chang Gung University; Taoyuan, Gueishan, Taiwan; §EVAS Therapeutics, LLC, Ballwin; and ∥Department of Radiology, Washington University School of Medicine, St Louis, MO.
出版信息
Ann Plast Surg. 2017 Mar;78(3 Suppl 2):S129-S134. doi: 10.1097/SAP.0000000000001018.
UNLABELLED
Appropriate antithrombotic therapy is critical for successful outcomes in reconstructive microsurgical procedures involving free tissue transfer. The annexin V-6L15 (ANV-6L15) fusion protein was developed as a targeted antithrombotic reagent. Annexin V specifically binds to exposed phosphatidylserine on apoptotic or injured cells, and prevents coagulation and cell adhesion, whereas 6L15 inhibits tissue factor-VIIa pathway within the coagulation cascade. The treatment efficacy of ANV-6L15 on rat island muscle and pedicled abdominal fasciocutaneous flaps following ischemic injury and ischemia-reperfusion injury (IRI) was evaluated.
MATERIALS AND METHODS
The effects of ANV-6L15 on survival of rat abdominal fasciocutaneous flaps subjected to 10 hours of critical ischemia were assessed on day 5. Near-IR imaging was applied to evaluate the distribution of ANV-6L15 and flap perfusion. The rat cremaster muscle island flap was used to evaluate the effect of ANV-6L15 on IRI-induced leukocyte-endothelial interactions via intravital microscopy. 2,3,5 triphenyl-tetrazolium chloride assay was used to determine the ratio between live-versus-dead tissue.
RESULTS
ANV-6L15 significantly increased the ratio of viable tissue (68.5 ± 9.79% vs 84.8 ± 5.14%, P < 0.05), and promoted survival of rat pedicled abdominal flaps (59.3 ± 6.86 vs. 47.0 ± 8.67, P < 0.05). Intravital microscopy demonstrated a significant decrease in the number of adhesive leukocytes (1.8 ± 1.64 vs. 10.0 ± 6.32, P < 0.05), and the percentage change of functional capillaries (16.4 ± 15.1 vs. 47.3 ± 18.3, P < 0.05) in ANV-6L15-treatment group.
CONCLUSIONS
ANV-6L15 promoted survival of ischemic rat cremaster muscle and abdominal fasciocutaneous flaps and ameliorated leukocyte-related IRI. Future evaluation of potential clinical application of ANV-6L15 is warranted as a flap treatment adjunct.
未标记
在涉及游离组织移植的重建显微外科手术中，适当的抗血栓治疗对于取得成功的手术结果至关重要。膜联蛋白V-6L15（ANV-6L15）融合蛋白被开发为一种靶向抗血栓试剂。膜联蛋白V特异性结合凋亡或受损细胞上暴露的磷脂酰丝氨酸，并防止凝血和细胞粘附，而6L15抑制凝血级联反应中的组织因子-VIIa途径。评估了ANV-6L15对大鼠岛状肌和带蒂腹部筋膜皮瓣在缺血性损伤和缺血再灌注损伤（IRI）后的治疗效果。
材料与方法
在第5天评估ANV-6L15对经历10小时严重缺血的大鼠腹部筋膜皮瓣存活的影响。应用近红外成像评估ANV-6L15的分布和皮瓣灌注情况。利用大鼠提睾肌岛状皮瓣通过活体显微镜评估ANV-6L15对IRI诱导的白细胞-内皮细胞相互作用的影响。采用2,3,5-三苯基氯化四氮唑法测定活组织与死组织的比例。
结果
ANV-6L15显著提高了存活组织的比例（68.5±9.79%对84.8±5.14%，P<0.05），并促进了大鼠带蒂腹部皮瓣的存活（59.3±6.86对47.0±8.67，P<0.05）。活体显微镜显示，ANV-6L15治疗组中粘附白细胞数量显著减少（1.8±1.64对10.0±6.32，P<0.05），功能性毛细血管的百分比变化也显著减少（16.4±15.1对47.3±18.3，P<0.05）。
结论
ANV-6L15促进了缺血大鼠提睾肌和腹部筋膜皮瓣的存活，并改善了与白细胞相关的IRI。作为皮瓣治疗辅助手段，有必要对ANV-6L15潜在的临床应用进行进一步评估。
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