Chicago, Ill. From the Department of Surgery, Division of Plastic and Reconstructive Surgery, Northwestern University, Feinberg School of Medicine.
Plast Reconstr Surg. 2012 Feb;129(2):252e-261e. doi: 10.1097/PRS.0b013e31823aea10.
3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, also known as statins, are the most commonly prescribed cholesterol-lowering medications in the world. Statins have been shown to inhibit connective tissue growth factor (CTGF) gene and protein expression in vitro, and previous studies in the authors' laboratory have demonstrated that CTGF plays a significant role in wound healing and scarring. The authors explore whether administration of various statins to healing wounds has any effect on hypertrophic scar formation using an established rabbit ear wounding model.
Punch wounds were made on the ears of 31 rabbits (n = 372 total wounds). Treatment wounds were injected with simvastatin, lovastatin, or pravastatin at low, medium, or high doses on postwounding days 15, 20, and 25, whereas control wounds were injected in a corresponding fashion. Wounds were harvested after 35 days for histomorphometric analysis.
Low-dose (40 μM) simvastatin, lovastatin, and pravastatin each demonstrated significant reductions in scar elevation index when compared with control: 21.9 percent (p = 0.03), 25.8 percent (p = 0.02), and 22.8 percent (p = 0.01), respectively. There were no significant differences in scar elevation index in the medium- (120 μM) and high-dose (400 μM) statin groups. Analysis of mRNA in a subset of rabbits treated with low-dose simvastatin demonstrated a significant reduction in CTGF expression (p = 0.009).
3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors reduce hypertrophic scar formation by means of CTGF inhibition when administered at low doses, and the novel application of these commonly prescribed medications may lead to innovative and effective antiscarring therapies.
3-羟基-3-甲基戊二酰辅酶 A 还原酶抑制剂，又称他汀类药物，是世界上最常用的降胆固醇药物。他汀类药物已被证明可抑制细胞外基质生长因子（CTGF）基因和蛋白的表达，作者实验室的先前研究表明 CTGF 在伤口愈合和瘢痕形成中起重要作用。作者使用已建立的兔耳创伤模型，探讨了将各种他汀类药物施用于愈合伤口是否会对肥厚性瘢痕形成产生影响。
在 31 只兔子的耳朵上制作穿孔伤（总伤口数为 372 个）。在创伤后第 15、20 和 25 天，治疗性伤口分别以低、中、高剂量注射辛伐他汀、洛伐他汀或普伐他汀，而对照性伤口则以相应方式注射。在 35 天后采集伤口进行组织形态计量学分析。
低剂量（40 μM）辛伐他汀、洛伐他汀和普伐他汀与对照组相比，瘢痕隆起指数均显著降低：分别为 21.9%（p = 0.03）、25.8%（p = 0.02）和 22.8%（p = 0.01）。中剂量（120 μM）和高剂量（400 μM）他汀组的瘢痕隆起指数无显著差异。对接受低剂量辛伐他汀治疗的部分兔子的 mRNA 进行分析，发现 CTGF 表达显著降低（p = 0.009）。
当以低剂量给药时，3-羟基-3-甲基戊二酰辅酶 A 还原酶抑制剂通过抑制 CTGF 的表达减少肥厚性瘢痕的形成，这些常用处方药的新应用可能会导致创新和有效的抗瘢痕治疗。
