背景:Peyronie病的特征是阴茎白膜中纤维化斑块的形成。有效的治疗方法有限,保证研究新的有希望的疗法,例如调节纤维化相关基因的microRNAs的应用。
目的:我们旨在研究在纤维蛋白诱导的Peyronie病大鼠模型中模拟microRNA-29b的治疗潜力。
方法:本研究分为两个阶段。为了建立最佳的佩罗尼病模型,在第0天和第5天,大鼠在白膜中接受了人纤维蛋白和凝血酶或盐溶液。通过表达和组织病理学分析进行动物模型验证。最新的是一位经验丰富的泌尿病理学家。验证后,我们在研究的第14,21和28天进行了microRNA-29b治疗.该阶段具有对照(生理盐水)和乱序(microRNA乱序)组。在第30天取出阴茎中轴,用于两个研究阶段的组织学检查和分子分析。
结果:对照组在动物模型验证中显示出典型的白膜组织学结构。在佩罗尼的疾病组中,苏木精和伊红和Masson三色染色方法显示间质炎症过程,伴随致密纤维化斑块以及胶原纤维紊乱.此外,我们发现,在Peyronie病组中,减少的microRNA-29b(p=0.05)与显著增加的COL1A1和转化生长因子β1基因和蛋白(p>0.05)相关。用模拟microRNA-29b刺激处理后,苏木精和伊红和Masson三色染色显示一个离散的和较不致密的纤维化斑块。该结果与COL1A1,COL3A1和转化生长因子β1基因和蛋白质的表达显着降低有关(p<0.05)。
结论:与对照组相比,纤维蛋白诱导的动物模型显示出明显的组织病理学和分子学变化,这表明我们的模型是合适的。先前的研究结果表明,microRNA-29b的表达增加与病理性纤维化的减少有关。在本研究中,用microRNA-29b处理降低了胶原蛋白和转化生长因子β1的基因和蛋白质表达。这项研究揭示了涉及分子靶标的Peyronie病的治疗潜力。
结论:MicroRNA-29b应用于大鼠白膜减毒纤维化,作为佩罗尼疾病管理的一种新的潜在策略。
BACKGROUND: Peyronie\'s disease is characterized by the formation of fibrotic plaques in the penile tunica albuginea. Effective treatments are limited, warranting the investigation of new promising therapies, such as the application of microRNAs that regulate fibrosis-related genes.
OBJECTIVE: We aimed to investigate the therapeutic potential of mimicking microRNA-29b in a fibrin-induced rat model of Peyronie\'s disease.
METHODS: The study was designed in two phases. To establish an optimal Peyronie\'s disease model, rats received either human fibrin and thrombin or saline solutions into the tunica albuginea on days 0 and 5. The animal model validation was done through expression and histopathological analyses, the latest by an experienced uropathologist. After validation, we performed microRNA-29b treatment on days 14, 21, and 28 of the study. This phase had control (normal saline) and scramble (microRNA scramble) groups. The mid-penile shaft was removed on day 30 for histological examination and molecular analyses in both study stages.
RESULTS: The control group displayed typical tunica albuginea histologic architecture in the animal model validation. In Peyronie\'s disease group, the Hematoxylin and eosin and Masson Trichrome staining methods demonstrated an interstitial inflammatory process with concomitant dense fibrotic plaques as well as disarrangement of collagen fibers. Additionally, we found out that reduced microRNA-29b (p = 0.05) was associated with significantly increased COL1A1 and transforming growth factor β1 genes and proteins (p > 0.05) in the Peyronie\'s disease group. After treatment with mimic microRNA-29b stimulation, the Hematoxylin & eosin and Masson Trichrome staining revealed a discrete and less dense fibrotic plaque. This result was associated with significantly decreasing expression of COL1A1, COL3A1, and transforming growth factor β1 genes and proteins (p < 0.05).
CONCLUSIONS: The fibrin-induced animal model showed significant histopathological and molecular changes compared to the Control group, suggesting that our model was appropriate. Previous findings have shown that increased expression of microRNA-29b was associated with decreased pathological fibrosis. In the present study, treatment with microRNA-29b decreased the gene and protein expression of collagens and transforming growth factor β1. This study reveals the therapeutic potential for Peyronie\'s disease involving molecular targets.
CONCLUSIONS: MicroRNA-29b application on the rat\'s tunica albuginea attenuated fibrosis, arising as a novel potential strategy for Peyronie\'s disease management.