INSERM, UMRS 1138, Centre de Recherche des Cordeliers, Sorbonne Université, Université Paris Cité, Paris, France.
Department of Basic Science, Thai Nguyen University of Agriculture and Forestry, Thainguyen, Vietnam.
Br J Pharmacol. 2022 Dec;179(23):5222-5232. doi: 10.1111/bph.15932. Epub 2022 Sep 2.
Delayed wound healing is among the deleterious consequences of over-activation of the mineralocorticoid receptor (MR) induced by topical dermocorticoids. The role of dermal inflammation and angiogenesis in the benefits of MR blockade is unknown.
Skin wounds were made on C57Bl6 mice after topical pretreatment with the dermocorticoid clobetasol. The impact of topical MR blockade by canrenoate on inflammation, angiogenesis, and the wound macrophage phenotype was analysed 5 days post-wounding. Similar experiments were conducted on mice with genetic deletion of the MR in myeloid cells.
Topical inhibition of the MR with canrenoate improved delayed wound healing through the resolution of prolonged inflammation in glucocorticoid-pretreated mouse skin. This effect was associated with a higher ratio of anti-inflammatory macrophages versus pro-inflammatory macrophages in wounds treated by canrenoate. Furthermore, MR blockade led to upregulated expression of pro-angiogenic factors and improved impaired angiogenesis in wounds of glucocorticoid-pretreated skin. Finally, deletion of MR expression by myeloid cells reproduced the benefits of topical pharmacological MR blockade.
Topical MR antagonism facilitates the switching of macrophages towards an anti-inflammatory phenotype, which improves prolonged inflammation and induces angiogenesis to accelerate wound healing delayed by glucocorticoid treatment.
局部皮质激素过度激活盐皮质激素受体（MR）可导致伤口愈合延迟，这是其有害后果之一。皮肤炎症和血管生成在 MR 阻断中的作用尚不清楚。
在 C57Bl6 小鼠皮肤局部预处理皮质激素氯倍他索后，造成皮肤伤口。在创伤后 5 天，分析局部 MR 阻断剂坎利酮对炎症、血管生成和伤口巨噬细胞表型的影响。在骨髓细胞中 MR 基因缺失的小鼠中进行了类似的实验。
坎利酮局部抑制 MR 可通过缓解糖皮质激素预处理小鼠皮肤中持续的炎症反应，改善延迟性伤口愈合。这种作用与坎利酮处理的伤口中抗炎性巨噬细胞与促炎性巨噬细胞的比例更高有关。此外，MR 阻断导致促血管生成因子的表达上调，并改善糖皮质激素预处理皮肤伤口中的受损血管生成。最后，骨髓细胞中 MR 表达的缺失重现了局部药理学 MR 阻断的益处。
局部 MR 拮抗作用促进了巨噬细胞向抗炎表型的转变，这改善了持续的炎症，并诱导了血管生成，从而加速了糖皮质激素治疗引起的伤口愈合延迟。
