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Herein, we reported a Nrf2 deletion diabetic mouse model induced by 8-week high-fat diet feeding combined with streptozocin (STZ) injection in Nrf2 knockout mice. Besides, wild-type mice (WT) were used as control group, wild-type mice with high-fat diet feeding and STZ injection as diabetic group (WT-T2DM), and Nrf2 knockout mice as Nrf2 deletion group (KO). The pathophysiological indexes and bladder morphology showed typical pathological features of diabetic bladder dysfunction in Nrf2 knockout diabetic mouse mice (KO-T2DM). ELISA results showed that advanced glycation end products (AGEs), ROS and malondialdehyde (MDA) levels in bladder was were up-regulated in both WT-T2DM and KO-T2DM group, while superoxide dismutase (SOD) and glutathione (GSH) levels decreased in these two groups. Compared with WT-T2DM group, western blot analysis of the bladder showed down-regulated expression of NQO1 and HO-1 in KO-T2DM group. However, apoptosis, marked by Caspase3 and bax\/bcl-2 ratio, was increased in KO-T2DM group. Neurotrophic factor (NGF) was significantly decreased in DBD model, and even much lower in KO-T2DM group. Collectively, our findings demonstrated that deletion of Nrf2 lead to severe oxidative stress, apoptosis, and lower level of neurotrophic factor, and provided the first set of experimental evidence, in a mouse model, to support Nrf2 as a promising target for DBD.<\/jats:p>","DOI":"10.1007\/s11255-024-04064-y","type":"journal-article","created":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T11:01:59Z","timestamp":1716289319000},"page":"3231-3240","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Deletion of Nrf2 induced severe oxidative stress and apoptosis in mice model of diabetic bladder dysfunction"],"prefix":"10.1007","volume":"56","author":[{"given":"Lei","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiaho","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guanyu","family":"Ren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qixiang","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinhui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenghua","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiyong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,5,21]]},"reference":[{"key":"4064_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2021.109119","volume":"183","author":"H Sun","year":"2022","unstructured":"Sun H, Saeedi P, Karuranga S et al (2022) IDF diabetes atlas: global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. 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