Department of Physiology and Pathology, Araraquara School of Dentistry, University of São Paulo State, UNESP, Humaitá St., 1680 - Center, Araraquara, SP, 14801-903, Brazil.
Department of Stomatology, Federal University of Paraná, UFPR, Pref. Lothário Meissner Av., 632 - Center, Curitiba, PR, 80210-170, Brazil.
Inflamm Res. 2022 Apr;71(4):473-483. doi: 10.1007/s00011-022-01553-7. Epub 2022 Mar 30.
The aim of this study was to evaluate the effects of both testosterone depletion and supraphysiological testosterone supplementation in the early phase of an animal cutaneous wound healing model in comparison with the physiological hormonal condition.
Forty rats were distributed into the following four groups: Control, Orchiectomy (OCX), Durateston (Dura) and OCX+Dura. On day 1, the testicles were removed (OCX group) and the rats (Dura group) received a supraphysiological dose (250 mg/kg) of exogenous testosterone weekly. After 15 days a full-thickness excisional skin wound was created in all animals, which was healed by the second intention for 7 days. On day 22, the rats were euthanatized and the wounds were harvested for histopathological evaluation, immunohistochemistry analyses and multiplex immunoassay. One-way ANOVA and post-hoc Tukey tests were performed.
It was found that the supraphysiological testosterone level increased extracellular matrix deposition, promoted higher blood vessel formation and reduced wound contraction (p < 0.05). Additionally, it also stimulated PCNA-positive fibroblasts and KGF-positive cells (p < 0.05), while orchiectomy reduced the expression of IL-6 and TNF-α and increased VEGF and PDGF (p < 0.05) .
In conclusion, the results provide evidence that supraphysiological testosterone supplementation plays a positive role in the early phase of cutaneous wound healing, thus improving granulation tissue maturation through the enhancement of angiogenesis.
本研究旨在评估去势和超生理睾酮补充对动物皮肤创伤愈合模型早期的影响，并与生理激素状态进行比较。
将 40 只大鼠随机分为以下四组：对照组、去势组（OCX）、Durateston 组（Dura）和 OCX+Dura 组。第 1 天，切除睾丸（OCX 组），并给大鼠（Dura 组）每周给予超生理剂量（250mg/kg）的外源性睾酮。15 天后，所有动物均进行全层切开皮肤创伤，通过二期愈合 7 天。第 22 天，处死大鼠，采集伤口进行组织病理学评估、免疫组织化学分析和多重免疫测定。采用单因素方差分析和事后 Tukey 检验。
发现超生理睾酮水平增加了细胞外基质的沉积，促进了更高的血管形成，并减少了伤口收缩（p<0.05）。此外，它还刺激了 PCNA 阳性成纤维细胞和 KGF 阳性细胞（p<0.05），而去势则降低了 IL-6 和 TNF-α的表达，增加了 VEGF 和 PDGF（p<0.05）。
总之，这些结果提供了证据表明，超生理睾酮补充在皮肤创伤愈合的早期阶段发挥积极作用，通过增强血管生成来改善肉芽组织成熟。
