Department of Plastic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, PR China; Department of Plastic Surgery, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang Province, PR China.
Department of Plastic Surgery, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang Province, PR China.
Biomed Pharmacother. 2019 Oct;118:109394. doi: 10.1016/j.biopha.2019.109394. Epub 2019 Aug 31.
The renin-angiotensin system (RAS) plays an important role in scar formation. We have previously shown that oral administration of ramipril and losartan could inhibit scarring. For easier application, here we developed a series of topical ramipril and losartan creams in different concentrations and formulations to explore the effect on scar formation in a C57BL/6 mouse scar model. The harvested scar tissues were analyzed with H&E staining, Masson staining and immunohistochemical staining. We found the group treated with 0.2% losartan urea cream (Prep. 1) or 0.1% ramipril cream (Prep. 2) had significantly smaller scars compared to the negative control, while the proliferation of fibroblasts was less active and the collagen fibers were more regular; both groups showed similar efficacy with the positive control (triamcinolone acetonide urea). We also found that drug transdermalness couldn't directly determine the efficacy. Our findings indicate that local application of angiotensin converting enzyme inhibitor drugs (ACEIs) and angiotensin receptor blocker drugs (ARBs) can reduce scarring by reducing the expression of collagen I, collagen III, phosphorylated small mothers against decapentaplegic 3 (p-Smad3) and transforming growth factor-β 1 (TGF-β1). This may provide new insight on scar treatment in clinic.
肾素-血管紧张素系统（RAS）在瘢痕形成中起重要作用。我们之前的研究表明，雷米普利和氯沙坦的口服给药可抑制瘢痕形成。为了便于应用，我们在此开发了一系列不同浓度和配方的局部雷米普利和氯沙坦乳膏，以探索其对 C57BL/6 小鼠瘢痕模型中成纤维细胞增殖和胶原纤维排列的影响。对采集的瘢痕组织进行 H&E 染色、Masson 染色和免疫组织化学染色分析。结果发现，与阴性对照组相比，0.2%氯沙坦尿素乳膏（Prep.1）或 0.1%雷米普利乳膏（Prep.2）处理组的瘢痕明显更小，成纤维细胞增殖活性较低，胶原纤维更规则；与阳性对照组（曲安奈德尿素）相比，两组均表现出相似的疗效。我们还发现，药物经皮渗透性不能直接决定疗效。我们的研究结果表明，局部应用血管紧张素转换酶抑制剂（ACEI）和血管紧张素受体阻滞剂（ARB）可以通过降低胶原 I、胶原 III、磷酸化 Smad3（p-Smad3）和转化生长因子-β1（TGF-β1）的表达来减少瘢痕形成。这可能为临床瘢痕治疗提供新的思路。
