Departments of Medicine, Pathology, and Veterinary Medicine, Columbia University, New York City, NY, USA.
Int Wound J. 2023 Mar;20(3):678-686. doi: 10.1111/iwj.13909. Epub 2022 Aug 9.
Receptor for Advanced Glycated End-products (RAGE) is highly expressed in diabetes and impairs wound healing. We proposed that administering an antibody that blocks RAGE will hasten the healing of dorsal wounds in diabetic pigs compared with a non-immune IgG. Two purpose-bred diabetic (D) Yucatan minipigs (Sinclair, Auxvasse MO) each underwent 12 2 × 2 cm full thickness dorsal wounds: four wounds received decellularized porcine skin patches (Xylyx Bio, Bklyn NY): four anti-RAGE Ab (CR-3) infused patches, four saline infused patches and four wounds were left open. One pig received anti-RAGE Ab (CR-3) 1 mg/kg IM q 10 days and other received non-immune IgG. Wounds were measured at 2 and 4 weeks followed by euthanasia and wound harvesting. At 2 weeks few of the patches appeared to be incorporated into the wound. By 4 weeks all patches in pigs treated systemically with CR-3 were detached and the wounds almost healed. For all 24 wounds for both pigs regardless of presence of patch or type of patch, the average IgG treated pig wound size at 4 weeks was 69.2 ± 14.6% of initial size and the average CR-3 treated pig wound size was 40.9 ± 11.3% of initial size (P = 0.0002). Quantitative immunohistology showed greater staining for collagen in the CR-3 treated wounds compared with IgG treated. Staining was positive for RAGE, Mac, and IL-6 in the IgG treated wounds and negative in the CR-3 treated wounds. From these pilot experiments, we conclude that a RAGE blocking antibody given parenterally improved wound healing in a diabetic pig while patches were not effective.
晚期糖基化终产物受体（RAGE）在糖尿病中高度表达，并且会损害伤口愈合。我们提出，与非免疫 IgG 相比，给予阻断 RAGE 的抗体将加速糖尿病猪背部伤口的愈合。两只专门培育的糖尿病（D）尤卡坦迷你猪（Sinclair，Auxvasse MO）每只背部都有 12 个 2×2 cm 的全层伤口：4 个伤口接受脱细胞猪皮贴片（Xylyx Bio，Bklyn NY）：4 个抗 RAGE Ab（CR-3）输注贴片，4 个盐水输注贴片，4 个伤口未处理。一只猪接受抗 RAGE Ab（CR-3）1 mg/kg 肌肉注射 q 10 天，另一只接受非免疫 IgG。在 2 周和 4 周时测量伤口，然后进行安乐死和伤口采集。在 2 周时，很少有贴片似乎被整合到伤口中。到 4 周时，用 CR-3 全身治疗的猪的所有贴片均已脱落，伤口几乎愈合。对于两只猪的所有 24 个伤口，无论是否有贴片或贴片类型如何，在第 4 周时，接受 IgG 治疗的猪的平均伤口大小为初始大小的 69.2±14.6%，而接受 CR-3 治疗的猪的平均伤口大小为初始大小的 40.9±11.3%（P=0.0002）。定量免疫组织化学显示，CR-3 治疗的伤口中胶原蛋白染色更强，而 IgG 治疗的伤口中 RAGE、Mac 和 IL-6 染色阳性，CR-3 治疗的伤口中染色阴性。从这些初步实验中，我们得出结论，给予 RAGE 阻断抗体可改善糖尿病猪的伤口愈合，而贴片无效。
