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.
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.
复制标题
包含膜联蛋白 V 和 Kunitz 抑制剂结构域的新型损伤位点靶向融合蛋白可改善缺血再灌注损伤并促进缺血性大鼠腹部皮瓣的存活。
DOI：
10.1097/sap.0000000000001018
复制
发表时间：
2017
影响因子：
1.5
通讯作者：
Cheng,Hui-Yun
中科院分区：
文献类型：
--
作者：
Shyu,VictorBong-Hang;Hsu,ChungEn;Wen,Chih-Jen;Wun,Tze-Chein;Tang,Rui;Achilefu,Samuel;Wei,Fu-Chan;Cheng,Hui-Yun
适当的抗血栓治疗对于涉及游离组织移植的重建显微外科手术的成功结局至关重要。膜联蛋白V-6L 15（ANV-6L 15）融合蛋白被开发为靶向抗血栓试剂。膜联蛋白V特异性结合凋亡或损伤细胞上暴露的磷脂酰丝氨酸，并防止凝血和细胞粘附，而6L 15抑制凝血级联中的组织因子-VIIa途径。ANV-6L 15对大鼠岛状肌和带蒂腹部筋膜皮瓣缺血性损伤和缺血再灌注损伤（IRI）后的治疗效果进行了评估。材料和方法ANV-6L 15对大鼠腹部筋膜皮瓣存活的影响进行了评估，10小时的严重缺血在第5天。应用近红外成像技术观察ANV-6L 15在皮瓣中的分布及皮瓣灌注情况。使用大鼠提睾肌岛状皮瓣通过活体显微镜评价ANV-6L 15对IRI诱导的白细胞-内皮相互作用的影响。结果ANV-6L 15能显著提高大鼠带蒂腹部皮瓣的成活率（68.5±9.79% vs.84.8 ± 5.14%，P< 0.05），促进皮瓣成活（59.3±6.86 vs.47.0 ±8.67，P< 0.05）。活体显微镜检查显示粘附性白细胞数量显著减少（1.8± 1.64vs.10.0 ±6.32，P< 0.05），功能性毛细血管百分比变化（16.4±15.1 vs. 47.3±18.3，结论ANV-6L 15可促进缺血大鼠提睾肌和腹部筋膜皮瓣的存活，改善白细胞减少，IRI相关ANV-6L 15作为皮瓣治疗辅助物的潜在临床应用的未来评价是必要的。
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 MethodsThe 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.ResultsANV-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.ConclusionsANV-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.