Ni Bin, Chen Zhengsen, Shu Le, Shao Yunpeng, Huang Yi, Tamrat Nebiyu Elias, Wei Zhongqing, Shen Baixin
Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210000, China.
Oxid Med Cell Longev. 2021 Jun 30;2021:4009308. doi: 10.1155/2021/4009308. eCollection 2021.
To investigate the protective effect and molecular mechanism of nuclear factor E2-related factor 2 (Nrf2) pathway in interstitial cystitis (IC).
We established a mouse model of IC by cyclophosphamide (CYP) in wild-type mice and Nrf2 gene knockout mice. We examined the histological and functional alterations, the changes of oxidative stress markers, and the expression of the antioxidant genes downstream of Nrf2 pathway.
After CYP administration, the mice showed urinary frequency and urgency, pain sensitization, decreased contractility, bladder edema, and oxidative stress disorder. Notably, the Nrf2 CYP mice had more severe symptoms. The mRNA and protein levels of antioxidant genes downstream of Nrf2 pathway were significantly upregulated in the Nrf2 CYP mice, while there were no significant changes in the Nrf2 CYP mice.
Nrf2 pathway protects bladder injury and ameliorates bladder dysfunction in IC, possibly by upregulating antioxidant genes and inhibiting oxidative stress.
研究核因子E2相关因子2（Nrf2）通路在间质性膀胱炎（IC）中的保护作用及分子机制。
我们通过环磷酰胺（CYP）在野生型小鼠和Nrf2基因敲除小鼠中建立了IC小鼠模型。我们检测了组织学和功能改变、氧化应激标志物的变化以及Nrf2通路下游抗氧化基因的表达。
给予CYP后，小鼠出现尿频、尿急、疼痛敏化、收缩力下降、膀胱水肿和氧化应激紊乱。值得注意的是，Nrf2基因敲除的CYP小鼠症状更严重。Nrf2通路下游抗氧化基因的mRNA和蛋白水平在野生型CYP小鼠中显著上调，而在Nrf2基因敲除的CYP小鼠中无显著变化。
Nrf2通路可保护膀胱损伤并改善IC中的膀胱功能障碍，可能是通过上调抗氧化基因和抑制氧化应激来实现的。
