Köktürk Sibel, Benli Erdal, Ayyıldız Ali, Cırrık Selma, Çetinkol Yeliz, Ayyıldız Sema Nur, Noyan Tevfik
Department of Histology and Embryology, Faculty of Medicine, Istanbul University, Istanbul, Turkey.
Department of Urology, Faculty of Medicine, Ordu University, Ordu, Turkey.
Rev Assoc Med Bras (1992). 2019 Mar;65(3):388-393. doi: 10.1590/1806-9282.65.3.388. Epub 2019 Apr 11.
We examined the effects of tadalafil, one of the phosphodiesterase type 5 (PDE5) inhibitors, in a rat model of with partial and complete unilateral ureteral obstruction (UUO).
The rats were divided into 5 groups: sham (n=6), partial unilateral ureteral obstruction (PUUO, n=6), PUUO with tadalafil treatment (PUUO+T; Cialis, 10 mg/72 h, intragastric; Lilly, Indianapolis, Indiana, USA), complete unilateral ureteral obstruction (CUUO, n=6), and CUUO with tadalafil treatment (CUUO+T).
Fifteen days after the UUO, the ureter presented changes in the layers of urothelium and significant infiltration of inflammatory cells in the PUUO and CUUO groups. Compared with the sham, PUUO and CUUO groups had severe increased inflammatory cell infiltration. The urothelial epithelium exhibited cell degeneration and loss because of the swollen, atrophic, and denuded epithelial cells in the PUUO and CUUO groups. In the PUUO+T and CUUO+T groups, the urothelium revealed less epithelial cell degeneration and loss.The expressions of α-smooth muscle actin (α-SMA) and transforming growth factor-β (TGF-β) exhibited up-regulation in the PUUO and CUUO groups. The expression of TGF-β decreased positively correlated with that of α-SMA in the tadalafil therapy groups, PUUO+T and CUUO+T.
The phosphodiesterase type 5 inhibitor's tadalafil reduced expressions of α-SMA and TGF-β in the obstructed ureters, measured by biochemical examinations. In addition, tadalafil decreased urothelium degeneration due to the decreased epithelial cell loss and inflammatory cell infiltration. Our results show that tadalafil prevents or slows down the onset of ureter inflammation and urothelial degeneration in rats with UUO.
我们在大鼠部分性和完全性单侧输尿管梗阻（UUO）模型中研究了5型磷酸二酯酶（PDE5）抑制剂之一他达拉非的作用。
将大鼠分为5组：假手术组（n = 6）、部分性单侧输尿管梗阻组（PUUO，n = 6）、他达拉非治疗的部分性单侧输尿管梗阻组（PUUO+T；希爱力，10 mg/72 h，灌胃；礼来公司，美国印第安纳州印第安纳波利斯）、完全性单侧输尿管梗阻组（CUUO，n = 6）以及他达拉非治疗的完全性单侧输尿管梗阻组（CUUO+T）。
UUO术后15天，输尿管出现尿路上皮层变化，PUUO组和CUUO组有明显的炎性细胞浸润。与假手术组相比，PUUO组和CUUO组的炎性细胞浸润严重增加。由于PUUO组和CUUO组上皮细胞肿胀、萎缩和剥脱，尿路上皮表现出细胞变性和缺失。在PUUO+T组和CUUO+T组中，尿路上皮显示出较少的上皮细胞变性和缺失。α-平滑肌肌动蛋白（α-SMA）和转化生长因子-β（TGF-β）的表达在PUUO组和CUUO组中上调。在他达拉非治疗组PUUO+T和CUUO+T中，TGF-β表达的降低与α-SMA的表达呈正相关。
通过生化检测发现，5型磷酸二酯酶抑制剂他达拉非降低了梗阻输尿管中α-SMA和TGF-β的表达。此外，他达拉非减少了上皮细胞丢失和炎性细胞浸润，从而减轻了尿路上皮变性。我们的结果表明，他达拉非可预防或减缓UUO大鼠输尿管炎症和尿路上皮变性的发生。
