Development of male and female models of long urethral strictures in swine.

Development of male and female models of long urethral strictures in swine.
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DOI:
10.1016/j.sopen.2023.11.002
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发表时间:
2023-12
影响因子:
1.4
通讯作者:
Mauney, Joshua R.
Mauney, Joshua R.
中科院分区:
其他
文献类型:
--
作者:
Gundogdu, Gokhan;Nguyen, Travis;Eijansantos, Mando;Chaudhuri, Ambika;Barham, David;Gelman, Joel;Mauney, Joshua R.

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临床前动物模型,模拟的尺寸长尿道狭窄(>2厘米长),在临床上遇到的是必要的,以评估未来的移植设计尿道成形术。本研究的目的是开发长尿道狭窄(长度<4cm)的雄性和雌性猪模型,并表征不同性别之间医源性狭窄形成的组织学和功能结局。通过电凝法在雄性和雌性猪(每种性别N = 4)中产生超过5-6 cm长的节段的局灶性部分厚度尿道损伤,并通过尿道镜检查和逆行尿道造影术监测狭窄形成的程度长达6周。在狭窄确认后处死动物,并对狭窄和未受伤的对照尿道段进行组织学、免疫组织化学和组织形态学分析,以描述伤口愈合反应。术后2周时,在所有雌性猪中检测到尿道狭窄形成,在3.2 ± 1.8周时,100%的雄性猪中检测到尿道狭窄形成。雄性和雌性猪的尿道狭窄的平均长度为1.4cm。观察到两种性别之间狭窄严重程度的显著差异,与对照组相比,雄性动物表现出显著的尿道狭窄和α-平滑肌肌动蛋白+平滑肌束丢失,而雌性动物主要表现出泛细胞角蛋白+上皮缺陷以及功能性尿道梗阻。电凝损伤足以在雄性和雌性猪中产生长的尿道狭窄,并且观察到狭窄的严重程度和尿道阻塞的性质取决于性别。动物方案:AUP-19-150。建立了猪长尿道狭窄的新型雄性和雌性模型,以表征不同性别之间医源性狭窄形成的组织学和功能结局。
Preclinical animal models which mimic the dimensions of long urethral strictures (>2 cm in length) encountered in the clinic are necessary to evaluate prospective graft designs for urethroplasty. The purpose of this study was to develop both male and female porcine models of long urethral strictures (∼4 cm in length) and characterize histological and functional outcomes of iatrogenic stricture formation between genders. Focal, partial thickness urethral injuries were created over 5–6 cm long segments in male and female swine (N = 4 per gender) via electrocoagulation and the degree of stricture formation was monitored for up to 6 weeks by urethroscopy and retrograde urethrography. Animals were sacrificed following stricture confirmation and histological, immunohistochemical, and histomorphometric analyses were performed on strictured and uninjured control urethral segments to profile wound healing responses. Urethral stricture formation was detected in all female swine by 2 weeks and 100 % of male swine at 3.2 ± 1.8 weeks, post-operatively. The mean length of urethral strictures in both male and female swine was ∼4 cm. Substantial variations in the degree of stricture severity between sexes were observed with males exhibiting significant urethral stenosis and loss of α-smooth muscle actin+ smooth muscle bundles in comparison to controls, while females primarily displayed defects in pan-cytokeratin+ epithelia as well as functional urethral obstruction. Electrocoagulation injury is sufficient to produce long urethral strictures in male and female swine and the degree of stricture severity and nature of urethral obstruction was observed to be dependent on gender. Animal Protocol: AUP-19-150. Novel male and female models of long urethral strictures in swine were created to characterize histological and functional outcomes of iatrogenic stricture formation between genders.
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