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首页> 外文期刊>Journal of dermatological science >Simvastatin ointment, a new treatment for skin inflammatory conditions
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Simvastatin ointment, a new treatment for skin inflammatory conditions

机译：辛伐他汀软膏，一种治疗皮肤炎症的新方法

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Background: Statins represent a class of drugs that effectively lowers cholesterol, however they also possess pleiotropic effects, like promotion of angiogenesis, prevention of bone loss, immunomodulatory and anti-inflammatory effects. Objectives: Thus, the aim of this study was to investigate the activity of simvastatin topically applied in mice in acute and chronic skin inflammation models. Methods: Skin inflammation was induced in mice ears by topical application of 12-O-tetradecanoylphorbol acetate (TPA). In the acute model, ear oedema was measured by the increase of ear thickness 6. h after TPA (2.5μg/ear). The chronic inflammatory process was induced by multiple applications of TPA (2.0μg/ear) for nine alternate days, and the oedema was measured daily as the increase in ear thickness. Results: Topical treatment was applied immediately after TPA in acute model or started at 5th day of chronic experiment. For acute model treatment was simvastatin (0.24, 0.71 and 2.40μM), dexamethasone (0.13μM), both in acetone or vehicle alone (acetone). In chronic model simvastatin (1% and 3%) and dexamethasone (0.5%) were incorporated in ointment preparations, and a group received ointment alone (vehicle). Samples of ear tissue (6mm) were taken from acute and chronic models, weighted and prepared for histological analysis and myeloperoxidase (MPO) enzymatic activity evaluation. Application of simvastatin in acetone reduced the ear oedema after a single TPA application in a dose dependent manner [ID 50 of 0.47 (0.22-1.13) μM], and the MPO enzymatic activity up to 61±10%. Also, both simvastatin ointment preparations 1% and 3% reduced acute TPA-induced ear oedema in 55±7% and 65±8%, respectively. In the chronic model, simvastatin ointment 1% was able to reduce ear oedema (25±3%) and ear weight (10±1%), though 3% formulation augmented both parameters. Histological analysis revealed a reduction of swelling and leukocyte migration in the acute model for both the formulations of simvastatin (1% and 3%), while in chronic model simvastatin 1% decreased ear swelling and epidermal thickness, but simvastatin 3% increased both parameters. Conclusion: The results confirm the anti-inflammatory activity of simvastatin when applied topically in both acute and chronic models of skin inflammation. Besides, the formulation of simvastatin ointment 1% shows to be a very effective formulation for a chronic usage.
机译：背景：他汀类药物代表一类可有效降低胆固醇的药物，但它们也具有多效作用，如促进血管生成，预防骨质流失，免疫调节和抗炎作用。目的：因此，本研究的目的是研究在急性和慢性皮肤炎症模型中局部应用辛伐他汀的小鼠的活性。方法：局部应用醋酸十二烷氧十四烷酰佛波醇（TPA）引起小鼠耳朵皮肤发炎。在急性模型中，TPA后2.5小时（2.5μg/耳），通过耳厚度的增加来测量耳水肿。连续9天连续多次使用TPA（2.0μg/耳）诱发慢性炎症过程，并每天测量耳廓厚度的增加引起的水肿。结果：急性模型中TPA后立即应用局部治疗，或在慢性实验的第5天开始局部治疗。对于急性模型治疗，是辛伐他汀（0.24、0.71和2.40μM），地塞米松（0.13μM），均在丙酮或仅在媒介物中（丙酮）服用。在慢性模型中，辛伐他汀（分别为1％和3％）和地塞米松（0.5％）被掺入软膏制剂中，一组仅接受软膏（载体）。从急性和慢性模型中提取耳组织样品（6毫米），称重并准备用于组织学分析和髓过氧化物酶（MPO）酶活性评估。辛伐他汀在丙酮中的施用以剂量依赖的方式[ID 50为0.47（0.22-1.13）μM]减少了单次TPA施用后的耳部水肿，MPO的酶活性高达61±10％。同样，两种辛伐他汀软膏制剂分别将1％和3％的急性TPA诱导的耳部水肿减少55±7％和65±8％。在慢性模型中，辛伐他汀软膏1％能够减轻耳部水肿（25±3％）和耳朵重量（10±1％），尽管3％的制剂可以同时增加这两个参数。组织学分析显示，两种模型的辛伐他汀制剂（1％和3％）在急性模型中肿胀和白细胞迁移减少，而在慢性模型中，辛伐他汀1％降低耳肿胀和表皮厚度，但辛伐他汀3％升高两个参数。结论：该结果证实了辛伐他汀在急性和慢性皮肤炎症模型中局部应用时的抗炎活性。此外，辛伐他汀软膏1％的配方对长期使用非常有效。

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