Hypothesis / aims of study
Pelvic ischemia induces bladder overactivity by stimulating the bladder and its afferent nerves. Nuclear factor erythroid 2-related factor 2 (Nrf2) protects cells from oxidative stress; however, its role in the pathogenesis of ischemic bladder overactivity is unknown. This study examined the relationship between Nrf2 expression and bladder overactivity using a pelvic ischemia mouse model.
Study design, materials and methods
C57BL/6 mice and Nrf2 knockout (KO) mice were used in this study. Pelvic ischemia was induced by adding L-NG-nitroarginine methyl ester (L-NAME; 0.3 g/L) to their drinking water. On day 7, the blood flow in the capillaries on the bladder surface was measured using a charge-coupled device camera (ref. 1), cystometrography was performed in the awake condition (infusion speed 0.5 mL/h), and the bladder was excised for histological evaluation and to quantify oxidative stress markers.
Interpretation of results
Activation of the Nrf2 signaling pathway, which leads to the upregulation of antioxidative genes, has been reported to protect neurons against neurodegenerative diseases; to promote myocyte differentiation, muscle contractility, and metabolic properties in a diabetic muscle atrophy model; and to protect various cells from apoptosis. This study demonstrated that Nrf2 translocated from the cytoplasm to the nucleus in the pelvic ischemia groups. We interpret this as a response to protect organs from ischemic injury. Although bladder blood flow was altered similarly in both the normal and Nrf2 KO mice, ischemic damage and bladder overactivity were more apparent in the Nrf2 KO mice. These results suggest that Nrf2 plays an important role in the development of ischemia-induced bladder overactivity and could be a therapeutic target for overactive bladder associated with pelvic ischemia.