背景:远程缺血预处理(RIC)已被证明可以改善组织对缺血的抵抗力。本研究的目的是探讨RIC的影响及其关键因素,一氧化氮(NO),烧伤伤口的血管生成。
方法:无毛小鼠(n=48)的耳朵上的单侧烧伤是通过热空气射流以非接触方式产生的。在四个随机分组中,包括对照组(NoRIC组),单独RIC(RIConly组),RIC加NO供体(ISDN组),和RIC加NO合成酶抑制剂(L-NAME组),对血管生成的影响,血管直径,血流量,水肿形成,使用活体荧光显微镜在12天的时间内评估了白细胞-内皮细胞-细胞的相互作用。
结果:RIC显着改善了组织灌注(第3天:ISDN组显示基线的182%,RIC仅显示基线的200%[BL],P<0.001),而RIC并未改善血管生成(第12天的非灌注面积:所有组BL的平均52%,P>0.05)。ISDN的应用并没有进一步增强RIC的积极作用,而L-NAME的应用中和了RIC的作用。在RIConly组中观察到最明显的水肿形成(平均BL的145%,P≤0.001),而NoRIC组的水肿形成最少(第12天:BL的117%)。
结论:RIC导致组织灌注增加,这并没有导致血管生成的改善,这可能是由于RIC表现后水肿形成增加。本研究的结果不支持建立烧伤伤口的因果治疗策略,包括RIC。
Remote ischemic conditioning (RIC) has been shown to improve tissue resilience against ischemia. The aim of this study was to investigate the influence of RIC and its key factor, nitrogen monoxide (NO), on angiogenesis in a burn wound.
A unilateral burn injury on the ear of hairless mice (n = 48) was generated via a hot air jet in a contact-free manner. In four randomized groups, including the control (NoRIC group), RIC alone (RIConly group), RIC plus NO donor (ISDN group), and RIC plus NO synthase inhibitor (L-NAME group), the impact on angiogenesis, vessel diameter, blood flow, edema formation, and leukocyte-endothelial-cell interaction was evaluated over a 12-d period using intravital fluorescence microscopy.
Tissue perfusion was significantly improved by RIC (Day 3: ISDN group showed 182% and RIConly group showed 200% of baseline [BL], P < 0.001), while angiogenesis was not improved by RIC (nonperfused area on Day 12: mean 52% of BL in all groups, P >0.05). The application of ISDN did not further enhance the positive effect of RIC, whereas the application of L-NAME neutralized the effect of RIC. The most pronounced edema formation was observed in the RIConly group (mean 145% of BL, P ≤0.001), while the NoRIC group showed the least edema formation (Day 12: 117% of BL).
RIC led to increased tissue perfusion, which did not result in improved angiogenesis, which may have been due to increased edema formation after RIC performance. The results of the present study do not support the establishment of a causal therapy strategy for burn wounds, including RIC.