Chen Shouzhen, Zhu Yaofeng, Liu Zhifeng, Gao Zhaoyun, Li Baoying, Zhang Dongqing, Zhang Zhaocun, Jiang Xuewen, Liu Zhengfang, Meng Lingquan, Yang Yue, Shi Benkang
Department of Urology, Qilu Hospital of Shandong University, Wenhua Xi Road, Jinan, Shandong Province, People's Republic of China.
Department of Urology, Qilu Hospital of Shandong University, Wenhua Xi Road, Jinan, Shandong Province, People's Republic of China; Department of Urology, The Central Hospital of Tai' an, Longtan Road, Tai' an, Shandong Province, People's Republic of China.
PLoS One. 2015 May 14;10(5):e0126457. doi: 10.1371/journal.pone.0126457. eCollection 2015.
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.
糖尿病（DM）诱发的膀胱功能障碍主要是由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。本研究聚焦于GSPE对链脲佐菌素诱导的糖尿病大鼠膀胱功能障碍的影响。给予GSPE 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得到显著改善。此外，GSPE治疗部分逆转了抗氧化酶（超氧化物歧化酶和谷胱甘肽过氧化物酶）活性紊乱和氧化应激水平异常的情况。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）检测，给予GSPE后，DM导致的膀胱细胞凋亡水平降低。此外，GSPE影响凋亡相关蛋白如Bax、Bcl-2和裂解的半胱天冬酶-3的表达。此外，GSPE对糖尿病大鼠的膀胱显示出神经保护作用，表现为神经生长因子（NGF）表达增加和神经生长因子前体（proNGF）表达降低。GSPE还激活了核红细胞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）水平升高。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以及激活Nrf2防御途径的能力有关。
