Grape Seed Proanthocyanidin Extract Ameliorates Diabetic Bladder Dysfunction via the Activation of the Nrf2 Pathway.
Grape Seed Proanthocyanidin Extract Ameliorates Diabetic Bladder Dysfunction via the Activation of the Nrf2 Pathway.
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葡萄籽原花青素提取物通过激活 Nrf2 通路改善糖尿病膀胱功能障碍
DOI：
10.1371/journal.pone.0126457
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Shi B
中科院分区：
文献类型：
--
作者：
Chen S;Zhu Y;Liu Z;Gao Z;Li B;Zhang D;Zhang Z;Jiang X;Liu Z;Meng L;Yang Y;Shi B
糖尿病（DM）引起的膀胱功能障碍主要是由于高血糖引起的长期氧化应激所致。据报道，葡萄籽原花青素提取物 (GSPE) 具有广泛的抗氧化应激药理和治疗特性。然而，其对糖尿病膀胱功能障碍的保护作用尚未明确。本研究重点探讨 GSPE 对链脲佐菌素诱导的糖尿病大鼠膀胱功能障碍的影响。 GSPE给药8周后，尿动力学分析和组织病理学表现均表明糖尿病大鼠的膀胱功能显着改善。此外，GSPE 治疗可部分逆转抗氧化酶（SOD 和 GSH-Px）活性紊乱和氧化应激水平异常。此外，根据末端脱氧核苷酸转移酶（TdT）介导的 dUTP 缺口末端标记（TUNEL）测定，施用 GSPE 后，DM 引起的膀胱细胞凋亡水平降低。此外，GSPE 还影响凋亡相关蛋白的表达，例如 Bax、Bcl-2 和 cleaved caspase-3。此外，GSPE 对糖尿病大鼠的膀胱具有神经保护作用，表现为神经生长因子 (NGF) 表达增加和神经生长因子前体 (proNGF) 表达减少。 GSPE 还激活核红细胞 2 相关因子 2 (Nrf2)，这是一种关键的抗氧化转录因子，同时下游血红素加氧酶-1 (HO-1) 升高。这些发现表明，GSPE 可以改善糖尿病大鼠的膀胱功能障碍并减少膀胱细胞凋亡，这一发现可能与其抗氧化活性和激活 Nrf2 防御途径的能力有关。
Diabetes Mellitus (DM)-induced bladder dysfunction is predominantly due to the long-term oxidative stress caused by hyperglycemia. Grape seed proanthocyanidin extract (GSPE) has been reported to possess a broad spectrum of pharmacological and therapeutic properties against oxidative stress. However, its protective effects against diabetic bladder dysfunction have not been clarified. This study focuses on the effects of GSPE on bladder dysfunction in diabetic rats induced by streptozotocin. After 8 weeks of GSPE administration, the bladder function of the diabetic rats was improved significantly, as indicated by both urodynamics analysis and histopathological manifestation. Moreover, the disordered activities of antioxidant enzymes (SOD and GSH-Px) and abnormal oxidative stress levels were partly reversed by treatment with GSPE. Furthermore, the level of apoptosis in the bladder caused by DM was decreased following the administration of GSPE according to the Terminal Deoxynucleotidyl Transferase (TdT)-mediated dUTP Nick-End Labeling (TUNEL) assay. Additionally, GSPE affected the expression of apoptosis-related proteins such as Bax, Bcl-2 and cleaved caspase-3. Furthermore, GSPE showed neuroprotective effects on the bladder of diabetic rats, as shown by the increased expression of nerve growth factor (NGF) and decreased expression of the precursor of nerve growth factor (proNGF). GSPE also activated nuclear erythroid2-related factor2 (Nrf2), which is a key antioxidative transcription factor, with the concomitant elevation of downstream hemeoxygenase-1 (HO-1). These findings suggested that GSPE could ameliorate diabetic bladder dysfunction and decrease the apoptosis of the bladder in diabetic rats, a finding that may be associated with its antioxidant activity and ability to activate the Nrf2 defense pathway.
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影响因子：
3.7
作者：
Roy Chowdhury S;Sengupta S;Biswas S;Sinha TK;Sen R;Basak RK;Adhikari B;Bhattacharyya A
通讯作者：
Bhattacharyya A
影响因子：
1.6
作者：
Cu, Xiao-pei;Li, Bao-ying;Lu, Mei
通讯作者：
Lu, Mei
神经生长因子和 P 物质：在糖尿病膀胱大鼠模型中的表达
影响因子：
2
作者：
Li, Yongzhi;Shi, Benkang;Liu, Yili
通讯作者：
Liu, Yili
DOI：
10.1016/j.juro.2009.08.070
发表时间：
2009-12
期刊：
The Journal of urology
影响因子：
--
作者：
Daneshgari F;Liu G;Birder L;Hanna-Mitchell AT;Chacko S
通讯作者：
Chacko S
影响因子：
1.6
作者：
Chen, Shouzhen;Zhu, Yaofeng;Shi, Benkang
通讯作者：
Shi, Benkang