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氯沙坦、雷帕霉素、强力霉素和肉毒杆菌毒素A的作用:大鼠实验性诱导尿道创伤模型

Effects of Losartan, Rapamycin, Doxycycline and botulinum toxin A: an experimentally induced urethral trauma model in rats.

作者信息

Baltİk Mücahit, Ergün Osman, Aslan Koşar Pınar, Onaran İbrahim, Tepebaşi Muhammet Yusuf

机构信息

Medical Faculty, Department of Urology, Süleyman Demirel University, Isparta, Turkey.

Medical Faculty, Department of Medical Biology, Süleyman Demirel University, Isparta, Turkey.

出版信息

J Mol Histol. 2025 Jul 9;56(4):221. doi: 10.1007/s10735-025-10476-6.

DOI:10.1007/s10735-025-10476-6
PMID:40632326
Abstract

To assess the antifibrotic efficacy of losartan, rapamycin, doxycycline, and botulinum toxin A (BTX-A) in an experimentally induced urethral trauma rat model. Sixty male rats were assigned to six groups; sham (n = 10), stricture (n = 10), losartan (n = 10), rapamycin (n = 10), doxycycline (n = 10), and BTX-A (n = 10). The sham group was exposed to only a penoscrotal incision. In the other groups, 10 W electrocoagulation with a duration of one second was applied at 5 mm intervals to three points on the urethra. Ten units of BTX-A (0.5 ml) was injected into the submucosal tissue following electrocoagulation in the BTX-A group. Losartan (30 mg/kg/day), doxycycline (10 mg/kg/day), and rapamycin (2 mg/kg/day) were administered for 14 days postoperatively by oral gavage to the other three groups. The animals were sacrificed on the 14th days, and their urethral tissues were removed. All treatment groups exhibited superiority over the stenosis groups with improvements in fibrosis, inflammation, vascular congestion, epithelial degeneration, and submucosal hemorrhage (p < 0.001). The treatment groups emerged as superior to the stenosis group with decreased interleukin-1β expression (p < 0,001). The mean gene values improved significantly in all treatment groups compared with those in the stenosis group (p < 0.001). All treatment groups showed reduced fibrosis. This research is the first to use losartan and doxycycline in urethral stenosis. Further data are needed regarding the use of these drugs for urethral stenosis. Clinical trial number: not applicable.

摘要

评估氯沙坦、雷帕霉素、强力霉素和肉毒杆菌毒素A(BTX-A)在实验性诱导的尿道创伤大鼠模型中的抗纤维化疗效。将60只雄性大鼠分为六组;假手术组(n = 10)、狭窄组(n = 10)、氯沙坦组(n = 10)、雷帕霉素组(n = 10)、强力霉素组(n = 10)和BTX-A组(n = 10)。假手术组仅进行阴茎阴囊切口。在其他组中,以5毫米的间隔对尿道上的三个点进行持续一秒的10瓦电凝。在BTX-A组中,电凝后将10单位的BTX-A(0.5毫升)注射到黏膜下组织中。氯沙坦(30毫克/千克/天)、强力霉素(10毫克/千克/天)和雷帕霉素(2毫克/千克/天)在术后通过口服灌胃给予其他三组,持续14天。在第14天处死动物,并取出其尿道组织。所有治疗组在纤维化、炎症、血管充血、上皮变性和黏膜下出血方面均优于狭窄组(p < 0.001)。治疗组在白细胞介素-1β表达降低方面优于狭窄组(p < 0.001)。与狭窄组相比,所有治疗组的平均基因值均有显著改善(p < 0.001)。所有治疗组的纤维化均减少。本研究首次在尿道狭窄中使用氯沙坦和强力霉素。关于这些药物用于尿道狭窄还需要进一步的数据。临床试验编号:不适用。

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