尿道外口皮下注射透明质酸建立大鼠膀胱出口梗阻模型及效果评价

Urethralorifice hyaluronic acid injections:a novel animal model of bladder outlet obstruction

目的通过尿道外口皮下注射透明质酸的方法建立一种简单微创、重复性好的大鼠膀胱出口梗阻(BOO)动物模型,并与传统开放手术BOO动物模型进行比较,评估其梗阻效果及并发症情况。方法共40只成年雌性SD大鼠进行试验,随机分为3组,即尿道外口透明质酸注射组(简称注射组)、开放手术近端尿道结扎组(简称手术组)和对照组。注射组(n=15)采用0.2mL透明质酸在尿道外口皮下周围注射的方法建立模型;手术组(n=15)利用传统开放性近端尿道结扎的方法建立模型;另10只正常大鼠作为对照。4周后检测各组充盈性膀胱测压检测梗阻效果、术后并发症、膀胱重量、以及HE染色检测膀胱组织学改变。结果注射组较手术组的模型操作时间显著缩短(P<0.05),无切口感染和膀胱结石等并发症;充盈性膀胱测压结果提示:与对照组相比,注射组和手术组均检测到膀胱容量、排尿频率和残余尿量增加及储尿末期逼尿肌不稳定收缩的典型膀胱出口梗阻的尿动力学表现;注射组和手术组膀胱重量明显增加(P<0.05),HE染色可见梗阻后膀胱黏膜下及间质明显水肿、肌层厚度均显著高于对照组(P<0.05)。结论大鼠尿道外口透明质酸注射简单微创、并发症少、效果明确、可重复性好,是一种有效的膀胱出口梗阻动物模型。

Objective To reduce surgery trauma and achieve the effect of bladder outlet obstruction （BOO）, we explored a novel animal model by hyaluronic acid periurethral injection and compared the obstructive effects and complications of this model with traditional open partial proximal urethral obstruction surgery. Methods A total of 40 Sprague-Dawley female rats were divided into 3 groups.. 15 rats were subcutaneously injected with 0.2 mL hyaluronic acid at 5,7,12 o＇clock of urethral ori fice respectively, another 15 rats undertook traditional open partial proximal urethral obstruction surgery, and 10 normal rats were set as control. After 4 weeks, the bladder weight, complications, filling cystometric study and histopathological features were evaluated by hematoxylin and eosin （HE） staining in each group. Results Hyaluronic acid periurethral injection caused increased maximum cystometric capacity, maximum bladder pressure, micturation interval, and postvoid residual urine volume compared with control （P〈0.01）. Moreover, the injection group had significantly shorter operative time, less incidence of incision infection compared to the surgery group （P〈O. 01）. HE staining showed suburothelial and interstitial hyperemia edema and smooth muscle hypertrophy in both injection and surgery bladders, which could not been found in control group. There was a significant increase in the bladder weight and thickness of smooth muscle in the bladders of injection group and surgery group compared with control group （P〈0. 01）. Oonclusions Hyaluronic acid periurethral injection provided a simple and effective model of BOO with fewer complications and simpler process compared with traditional surgery model. It seems to be a useful research tool for understanding the pathophysiological change of 1300.