Lin Alpha Dian-Yu, Mannikarottu Anita, Kogan Barry A, Whitbeck Catherine, Leggett Robert E, Levin Robert M
Albany College of Pharmacy, 106 New Scotland Ave, Albany, NY 12208, USA.
Mol Cell Biochem. 2007 Feb;296(1-2):11-6. doi: 10.1007/s11010-005-9068-4. Epub 2007 Jan 3.
Ischemia/reperfusion (I/R) is a major etiological factor in the bladder dysfunctions observed in men with lower tract obstruction, women with postmenopausal incontinence and with aging. A standardized grape suspension protects the rabbit urinary bladder from both the contractile dysfunctions and the morphologic changes mediated by I/R. Using a model of in vivo bilateral ischemia/reperfusion, the current study investigated the effect of this grape suspension on the endogenous antioxidant defense systems.
24 NZW rabbits were separated into 6 groups of 4. Groups 1-3 were treated by gavage with aqueous grape suspensions; groups 4-6 received sugar-water vehicle. Groups 3 and 6 were controls. Groups 1 and 4 were subjected to bilateral ischemia for 2 h (I). Groups 2 and 5 underwent bilateral ischemia for 2 h and reperfusion for 1 week (I/R). For all rabbit bladders, the muscle and mucosa were separated by blunt dissection and analyzed separately. The effects of the various treatments on bladder antioxidant systems of cytoplasmic superoxide dismutase (Cu-Zn superoxide dismutase; SOD), and catalase (CAT) were evaluated.
The standardized grape suspension up-regulated both SOD and CAT activity of bladder muscle and mucosa in control animals. There were few differences in the grape suspension treated animals after ischemia, and in general the activities decreased following I/R.
Increases of SOD and CAT activity in control animals as a result of grape suspension suggest a greater antioxidant capacity. This increase in the antioxidant defense system may explain the increased protection of grape suspension in the face of ischemia and I/R. However, the activities of both enzyme systems decreased in the smooth muscle subjected to I/R showing that reperfusion damages these systems probably via oxidation damage to the enzymes themselves.
缺血/再灌注(I/R)是导致下尿路梗阻男性、绝经后尿失禁女性以及老年患者膀胱功能障碍的主要病因。标准化葡萄悬液可保护兔膀胱免受I/R介导的收缩功能障碍和形态学改变的影响。本研究采用体内双侧缺血/再灌注模型,探讨该葡萄悬液对内源性抗氧化防御系统的影响。
将24只新西兰白兔分为6组,每组4只。第1 - 3组经口灌胃给予葡萄水悬液;第4 - 6组给予糖水载体。第3组和第6组为对照组。第1组和第4组进行双侧缺血2小时(I)。第2组和第5组进行双侧缺血2小时并再灌注1周(I/R)。对所有兔膀胱,通过钝性分离将肌肉和黏膜分开并分别进行分析。评估不同处理对膀胱细胞质超氧化物歧化酶(铜锌超氧化物歧化酶;SOD)和过氧化氢酶(CAT)抗氧化系统的影响。
标准化葡萄悬液上调了对照动物膀胱肌肉和黏膜中SOD和CAT的活性。缺血后葡萄悬液处理的动物中差异不大,总体而言I/R后活性降低。
葡萄悬液使对照动物中SOD和CAT活性增加,提示抗氧化能力增强。抗氧化防御系统的这种增强可能解释了葡萄悬液在面对缺血和I/R时保护作用增强的原因。然而,I/R处理的平滑肌中这两种酶系统的活性均降低,表明再灌注可能通过对酶本身的氧化损伤破坏了这些系统。