Park H, Kyung Y S, Lee G
Department of Urology, Dankook University College of Medicine, Cheonan, Korea.
Department of Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Hum Exp Toxicol. 2016 Jun;35(6):613-22. doi: 10.1177/0960327115597466. Epub 2015 Sep 30.
Cyclophosphamide (CYP) induces urothelial injury and causes excretion of cellular exudates at 24 h, followed by rapid restoration at 72 h. We investigated the role of urinary uroplakin II (UPII) levels in a CYP-induced cystitis model. For the purpose of this study, 10 controls and 26 CYP-injected female Sprague Dawley rats were killed at 24 h and 72 h postinjection. The vesical weight, severity of hematuria, and expression of UPII in the urinary bladder and urine were measured. CYP decreased the level of vesical UPII messenger RNA at 24 h, followed by rapid recovery at 72 h. Contrary to the negligible levels of urinary UPII and hematuria in controls, CYP treatment abruptly increased the excretion of urinary UPII at 24 h. The excretion had subsided at 72 h. Similarly, severe hematuria was observed at 24 h, with improvement at 72 h. However, some rats still exhibited hematuria at 72 h. CYP caused increase in vesical weight. The vesical weight at 24 h after CYP injection was negatively correlated with the vesical UPII level. Rats with significant hematuria demonstrated higher urinary UPII levels than those with insignificant hematuria. Vesical UPII could be an important barrier for early CYP-related injury, while the levels of urinary UPII may be associated with the severity of hematuria during dynamic periods in the urothelium.
环磷酰胺(CYP)可导致尿路上皮损伤,并在24小时时引起细胞渗出物排泄,随后在72小时时迅速恢复。我们研究了尿路上皮蛋白II(UPII)水平在CYP诱导的膀胱炎模型中的作用。为了本研究的目的,在注射后24小时和72小时处死10只对照大鼠和26只注射CYP的雌性Sprague Dawley大鼠。测量膀胱重量、血尿严重程度以及膀胱和尿液中UPII的表达。CYP在24小时时降低了膀胱UPII信使核糖核酸水平,随后在72小时时迅速恢复。与对照组中可忽略不计的尿UPII水平和血尿不同,CYP处理在24小时时突然增加了尿UPII的排泄。这种排泄在72小时时已消退。同样,在24小时时观察到严重血尿,72小时时有所改善。然而,一些大鼠在72小时时仍表现出血尿。CYP导致膀胱重量增加。CYP注射后24小时的膀胱重量与膀胱UPII水平呈负相关。血尿明显的大鼠尿UPII水平高于血尿不明显的大鼠。膀胱UPII可能是早期CYP相关损伤的重要屏障,而尿UPII水平可能与尿路上皮动态期血尿的严重程度有关。