Laboratory for Wound Repair and Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.
PLoS One. 2013;8(3):e59979. doi: 10.1371/journal.pone.0059979. Epub 2013 Mar 25.
Approximately 15% of the United States population suffers from chronic kidney disease (CKD), often demonstrating an associated impairment in wound healing. This study outlines the development of a surgical murine model of CKD in order to investigate the mechanisms underlying this impairment.
CKD was induced in mice by partial cauterization of one kidney cortex and contralateral nephrectomy, modifying a previously published technique. After a minimum of 6-weeks, splinted, dorsal excisional wounds were created to permit assessment of wound healing parameters. Wounds were harvested on postoperative days (POD) 0, 3, 7, and 14 for histological, immunofluorescent, and quantitative PCR (qPCR).
CKD mice exhibited deranged blood chemistry and hematology profiles, including profound uremia and anemia. Significant decreases in re-epithelialization and granulation tissue deposition rates were found in uremic mice wounds relative to controls. On immunofluorescent analysis, uremic mice demonstrated significant reductions in cellular proliferation (BrdU) and angiogenesis (CD31), with a concurrent increase in inflammation (CD45) as compared to controls. CKD mice also displayed differential expression of wound healing-related genes (VEGF, IL-1β, eNOS, iNOS) on qPCR.
These findings represent the first reported investigation of cutaneous healing in a CKD animal model. Ongoing studies of this significantly delayed wound healing phenotype include the establishment of renal failure model in diabetic strains to study the combined effects of CKD and diabetes.
大约 15%的美国人口患有慢性肾病（CKD），通常伴有伤口愈合受损。本研究旨在开发一种 CKD 手术小鼠模型，以探讨其损伤的机制。
通过对一侧肾脏皮质进行部分烧灼和对侧肾切除术来诱导 CKD，改进了以前发表的技术。至少 6 周后，用夹板固定背部切口创，以评估伤口愈合参数。术后第 0、3、7 和 14 天分别采集伤口进行组织学、免疫荧光和定量 PCR（qPCR）分析。
CKD 小鼠表现出血液化学和血液学特征的紊乱，包括严重的尿毒症和贫血。与对照组相比，尿毒症小鼠的伤口再上皮化和肉芽组织沉积率显著降低。在免疫荧光分析中，尿毒症小鼠的细胞增殖（BrdU）和血管生成（CD31）明显减少，而炎症（CD45）增加，与对照组相比。qPCR 还显示 CKD 小鼠伤口愈合相关基因（VEGF、IL-1β、eNOS、iNOS）的差异表达。
这些发现代表了在 CKD 动物模型中对皮肤愈合的首次报道研究。对这种明显延迟的伤口愈合表型的持续研究包括建立糖尿病品系的肾衰竭模型，以研究 CKD 和糖尿病的联合影响。
