From the Departments of Orthopedics and Neurology, Peking University Third Hospital; Beijing Key Laboratory of Spinal Diseases.
Plast Reconstr Surg. 2020 Feb;145(2):433-443. doi: 10.1097/PRS.0000000000006502.
This study explored the effect of a single local intraosseous application of a small dose of simvastatin on the wound healing process in type 1 diabetic rats and related mechanisms.
The authors chose the streptozotocin-induced type 1 diabetic rat to establish a full-thickness dermal wound using a 12-mm-diameter sterile disposable punch. The rats (n = 32) were divided randomly into four groups: (1) normal control rats, (2) type 1 diabetic rats with intraosseous injection of hydrogel vehicle, (3) type 1 diabetic rats with intraosseous injection of simvastatin (0.5 mg), and (4) type 1 diabetic rats with intragastric administration of simvastatin (20 mg/kg per day). Wound closure was followed by digital planimetry. Mobilization of endothelial progenitor cells into the circulatory system was studied using fluorescence-activated cell sorting. Neovascularization was analyzed with immunofluorescence histochemical staining. The relative levels of adiponectin and stromal cell-derived factor 1 (SDF-1) in serum, bone, and wound tissues were examined by enzyme-linked immunosorbent assay and Western blot.
Diabetic rats exhibited impaired wound healing. Intraosseous administration of simvastatin accelerated wound healing beginning at day 4, and angiogenesis was more obvious than in the control group. Enzyme-linked immunosorbent assay revealed that adiponectin concentrations in the diabetic rats with intraosseous injection of hydrogel vehicle plus simvastatin 0.5-mg group were significantly higher compared with the diabetic rats with intraosseous injection of hydrogel vehicle group beginning at day 4. Intraosseous administration of simvastatin decreased the expression of adiponectin and SDF-1 in bone tissue but enhanced the expression of adiponectin in wounded skin.
A single local intraosseous application of simvastatin promotes wound healing in type 1 diabetic rat. The underlying mechanisms may be attributed to the regulation of the adiponectin/SDF-1 pathway, which plays a pivotal role in endothelial progenitor cell mobilization and angiogenesis.
本研究旨在探讨在 1 型糖尿病大鼠中，单次局部骨内给予小剂量辛伐他汀对伤口愈合过程的影响及其相关机制。
作者选择链脲佐菌素诱导的 1 型糖尿病大鼠，使用 12mm 直径无菌一次性打孔器制造全层皮肤创面。将大鼠（n=32）随机分为 4 组：（1）正常对照组；（2）骨内注射水凝胶载体的 1 型糖尿病组；（3）骨内注射辛伐他汀（0.5mg）的 1 型糖尿病组；（4）辛伐他汀（20mg/kg/天）灌胃的 1 型糖尿病组。通过数字绘图法监测伤口愈合情况。通过荧光激活细胞分选术研究内皮祖细胞向循环系统的动员情况。通过免疫荧光组织化学染色分析新生血管形成。通过酶联免疫吸附试验和 Western blot 检测血清、骨和伤口组织中脂联素和基质细胞衍生因子 1（SDF-1）的相对水平。
糖尿病大鼠的伤口愈合受损。骨内给予辛伐他汀从第 4 天开始加速伤口愈合，且血管生成更为明显。酶联免疫吸附试验显示，在骨内注射水凝胶载体加辛伐他汀 0.5mg 组的糖尿病大鼠中，脂联素浓度从第 4 天开始明显高于骨内注射水凝胶载体组。骨内给予辛伐他汀降低了骨组织中脂联素和 SDF-1 的表达，但增强了受伤皮肤中脂联素的表达。
单次局部骨内给予辛伐他汀可促进 1 型糖尿病大鼠的伤口愈合。其潜在机制可能与调节脂联素/SDF-1 通路有关，该通路在内皮祖细胞动员和血管生成中发挥关键作用。
