Sulforaphane improves voiding function via the preserving mitochondrial function in diabetic rats
Sulforaphane improves voiding function via the preserving mitochondrial function in diabetic rats
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DOI：
10.1016/j.jfma.2019.11.017
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发表时间：
2020-09-01
影响因子：
3.2
通讯作者：
Chien, Chiang-Ting
中科院分区：
文献类型：
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作者：
Lin, Chia-Fa;Chueh, Tsung-Hung;Chien, Chiang-Ting
背景：高血糖引起的氧化应激导致糖尿病(DM)所致的排尿功能障碍。我们探讨了抗氧化剂萝卜硫素(一种核因子-E2相关的核因子红系2(NRF-2)激活剂)是否可以改善糖尿病所致的膀胱功能障碍。用超灵敏化学发光仪测定膀胱液中的ROS。用Western blotting检测线粒体Bax和胞浆细胞色素c、抗氧化防御NRF-2/HO-1、内质网应激标志物ATF-6/CHOP和Caspase 3/PARP的表达。结果：DM大鼠膀胱ROS增加，线粒体Bax易位，胞浆细胞色素c释放，ATF-6/CHOP，caspase-3/PARP增加，导致排尿功能障碍，收缩间期延长，排尿时间延长。但萝卜硫素可显著增加NRF-2/HO-1轴的核表达，减少膀胱ROS含量，减少线粒体Bax易位，减少细胞色素c释放，减少ATF-6/CHOP和caspase3/PARP/细胞凋亡，从而缩短收缩间期和排尿时间，从而改善排尿功能。结论：萝卜硫素激活NRF-2/HO-1信号通路可保护线粒体功能，抑制DM诱导的ROS、内质网应激、细胞凋亡和排尿功能障碍。版权所有(C)2019，台湾医学会。爱思唯尔台湾有限责任公司出版。
Background: Hyperglycemia evoked oxidative stress contributing to diabetes (DM)-induced voiding dysfunction. We explored whether antioxidant sulforaphane,a NF-E2-related nuclear factor erythroid-2 (Nrf-2) activator, may ameliorate DM-induced bladder dysfunction.Methods: DM was induced by streptozotocin and sulforaphanewas administered before DM induction. Bladder reactive oxygen species (ROS) were determined by an ultrasensitive chemiluminescence analyzer. Mitochondrial function index mitochondrial Bax and cytosolic cytochrome c, antioxidant defense Nrf-2/HO-1, endoplasmic reticulum stress marker ATF-6/CHOP, and caspase 3/PARP were evaluated by Western blot.Results: DM increased Keap1 and reduced Nrf-2 expression, associated with increase of bladder ROS, mitochondrial Bax translocation, cytosolic cytochrome c release, ATF-6/CHOP, caspase-3/PARP in bladders which resulted in voiding dysfunction by increased intercontraction intervals and micturition duration. However, sulforaphanesignificantly increased nuclear Nrf-2/HO-1axis expression, decreased bladder ROS amount, mitochondrial Bax translocation, cytochrome c release, ATF-6/CHOP and caspase 3/PARP/apoptosis, thereby improved the voiding function by the shortened intercontraction intervals and micturition duration.Conclusion: We suggest that sulforaphanevia activating Nrf-2/HO-1 signaling preserved mitochondrial function and suppressed DM-induced ROS, endoplasmic reticulum stress, apoptosis and voiding dysfunction. Copyright (C) 2019, Formosan Medical Association. Published by Elsevier Taiwan LLC.