Matsumoto Seiji, Leggett Robert E, Levin Robert M
Division of Basic and Pharmaceutical Sciences, Albany College of Pharmacy, Albany, NY 12208, USA.
Mol Cell Biochem. 2003 Dec;254(1-2):347-51. doi: 10.1023/a:1027386204900.
There is increasing evidence that ischemia, reperfusion, and the generation of free radicals are major etiological factors in the progression of bladder dysfunction after partial outlet obstruction. In vitro studies demonstrated that the magnitude of contractile dysfunction following exposure of bladder smooth muscle to hypoxia followed by re-oxygenation was related to the level of lipid peroxidation indicating that membrane lipid peroxidation participated in the contractile failure induced. Recent studies demonstrated that incubation of isolated strips of bladder smooth muscle with hydrogen peroxide (H2O2) result in progressive contractile dysfunctions and is associated with progressive increases in MDA (peroxidation product). The current study investigates if feeding rabbits a diet high in vitamin E protects the bladder from the effects of in vitro H2O2. Sixty-four male New Zealand White rabbits were separated into two groups: The rabbits in group 1 were fed a normal diet (28 rabbits) whereas the rabbits in group 2 were placed on a diet enriched with alpha-tocopherol (36 rabbits). After 3 weeks on the normal or high E diet, each rabbit was anesthetized and the bladder excised and cut into 6 isolated strips of bladder detrusor. Each strip was mounted in individual 15 ml baths containing oxygenated Tyrode's solution. The contractile responses to field stimulation (FS), carbachol. and KCl were determined. The strips were washed and exposed to one of the following concentrations of hydrogen peroxide (H2O2): 0% (control), 0.0625, 0.125, 0.25, 0.5, 1.0 and 3.0% for a period of 1 h. At the end of the hour each strip was washed free of H2O2 and a second set of contractile responses were performed and compared to the first set. At the end of the experiment, each strip was frozen and stored at -70 degrees C for analysis of malondialdehyde (MDA) as a measure of peroxidation. In both groups, H2O2 produced similar dose dependent decreases in the contractile responses to all forms of stimulation. In the normal-diet group H2O2 produced a dose dependent increase in MDA formation, whereas in the high E group there were no increases in MDA at any concentration of H2O2. Feeding rabbits a diet high in vitamin E protected the bladder smooth muscle from peroxidation, but had no significant effect on the contractile dysfunctions mediated by direct incubation with H2O2.
越来越多的证据表明,缺血、再灌注和自由基的产生是部分出口梗阻后膀胱功能障碍进展的主要病因。体外研究表明,膀胱平滑肌暴露于缺氧后再复氧时收缩功能障碍的程度与脂质过氧化水平相关,这表明膜脂质过氧化参与了诱导的收缩功能衰竭。最近的研究表明,将分离的膀胱平滑肌条与过氧化氢(H2O2)一起孵育会导致渐进性收缩功能障碍,并与丙二醛(过氧化产物)的逐渐增加有关。本研究调查给兔子喂食富含维生素E的饮食是否能保护膀胱免受体外H2O2的影响。64只雄性新西兰白兔被分为两组:第1组的兔子喂食正常饮食(28只兔子),而第2组的兔子喂食富含α-生育酚的饮食(36只兔子)。在正常饮食或高E饮食3周后,每只兔子麻醉,切除膀胱并切成6条分离的膀胱逼尿肌条。每条肌条安装在含有充氧台氏液的单独15毫升浴槽中。测定对场刺激(FS)、卡巴胆碱和氯化钾的收缩反应。冲洗肌条并将其暴露于以下浓度之一的过氧化氢(H2O2):0%(对照)、0.0625%、0.125%、0.25%、0.5%、1.0%和3.0%,持续1小时。1小时结束时,每条肌条冲洗掉H2O2,进行第二组收缩反应并与第一组进行比较。实验结束时,将每条肌条冷冻并储存在-70℃用于分析丙二醛(MDA)作为过氧化的指标。在两组中,H2O2对所有形式刺激的收缩反应均产生类似的剂量依赖性降低。在正常饮食组中,H2O2使MDA形成呈剂量依赖性增加,而在高E组中,任何浓度的H2O2均未使MDA增加。给兔子喂食富含维生素E的饮食可保护膀胱平滑肌免受过氧化,但对直接与H2O2孵育介导的收缩功能障碍无显著影响。