Oxidative stress and neurodegeneration in the ischemic overactive bladder
Oxidative stress and neurodegeneration in the ischemic overactive bladder
复制标题
DOI：
10.1016/j.juro.2007.03.096
复制
发表时间：
2007-08-01
影响因子：
6.6
通讯作者：
Siroky, Mike B.
中科院分区：
文献类型：
--
作者：
Azadzoi, Kazem M.;Yalla, Subbarao V.;Siroky, Mike B.
目的：中枢和外周神经系统对缺血和氧化应激高度敏感。我们寻找氧化损伤的标志物，并检测兔缺血过度活动膀胱的神经细胞密度。材料和方法：在缺血诱导后8周和16周，通过膀胱测压记录过度活动和对照兔膀胱的血流和氧合情况。酶免疫分析法检测氧化产物，免疫组织化学染色检测神经细胞密度。逆转录-聚合酶链式反应检测神经生长因子及其受体p75的基因表达。在含H_2O_2的组织培养液中观察急性氧化应激的影响。结果：在缺血的膀胱中，过度的氧化应激产生了反复的缺血/再灌流和缺氧/复氧循环，导致氧化和亚硝化产物的产生。缺血8周的膀胱神经细胞密度与对照组相近，而缺血16周后神经细胞明显变性。神经生长因子基因水平在缺血诱导后第8周开始升高，但在第16周显着下降。缺血8周后p75基因表达水平下降，16周后仍低于对照组。急性氧化应激使培养上清液中神经生长因子蛋白释放减少。抗氧化酶过氧化氢酶对对照组织无明显影响，但能部分保护神经生长因子免受过氧化氢损伤。结论：缺血可能在膀胱神经病变中起一定作用。缺血条件下的过度活动会在膀胱中产生有害的氧化产物。膀胱缺血时的神经变性可能与营养缺乏、缺氧和过度活动引起的自由基有关。神经生长因子及其受体可能调节氧化损伤的神经反应。
Purpose: The central and peripheral nervous systems are highly sensitive to ischemia and oxidative stress. We searched for markers of oxidative injury and examined neural density in the rabbit ischemic overactive bladder.Materials and Methods: Blood flow and oxygenation were recorded during cystometrogram in overactive and control rabbit bladders at weeks 8 and 16 after the induction of ischemia. Oxidative products and neural density were assessed by enzyme immunoassay and immunohistochemical staining, respectively. Reverse transcriptase-polymerase chain reaction was done to determine the gene expression of nerve growth factor and its receptor p75. The effect of acute oxidative stress was examined in tissue culture medium containing H2O2.Results: Overactivity produced repeating cycles of ischemia/reperfusion and hypoxia/reoxygenation in the ischemic bladder, leading to oxidative and nitrosative products. Neural density in the 8-week ischemic bladder was similar to that in controls, while neurodegeneration was evident after 16 weeks of ischemia. Nerve growth factor gene levels initially increased at week 8 but significantly decreased at week 16 after the induction of ischemia. Gene levels of p75 decreased after 8 weeks and remained lower than in controls after 16 weeks of ischemia. Acute oxidative stress decreased nerve growth factor protein release in culture medium. The antioxidant enzyme catalase had no significant effect on control tissues but it partially protected nerve growth factor from H2O2 injury.Conclusions: Ischemia may have a role in bladder neuropathy. Overactivity under ischemic conditions produces noxious oxidative products in the bladder. Neurodegeneration in bladder ischemia may involve a lack of nutrients, hypoxia and overactivity induced free radicals. Nerve growth factor and its receptors may regulate neural reactions to oxidative injury.