シクロホスファミド誘発性膀胱機能障害に対する硫化水素の保護効果メカニズム

抄録

We have reported protective effect of NaHS [hydrogen sulfide (H₂S) donor] on cyclophosphamide (CYP)-induced rat bladder dysfunction by improving CYP-induced shortening of intercontraction intervals (ICI) and increases in non-voiding contractions (NVCs). In this study, we examined mechanisms of the protective effect. Nine-week-old male Wistar rats were pretreated with NaHS (10 μmol/kg, ip) or saline once daily for 7 days. CYP (150 mg/kg, ip) or saline had been injected 2 days before urodynamic experiments, and after the experiments, bladder tissues were collected to perform HE staining. In some rats, vehicle or capsaicin (CAP, 125 mg/kg, sc), which can desensitize CAP-sensitive afferent nerves, was pretreated 4 days before urodynamic experiments. In bladder tissues, CYP increased neutrophile infiltration, bleeding, and edema, but NaHS partially improved only the edema. CAP prolonged ICI and reduced NVCs in CYP-treated rats. NaHS-induced improvement of CYP-induced ICI shortening and NVC increasing was not detected in CAP-treated rats. These data suggest that NaHS showed protective effect on bladder dysfunction in CYP-treated rats via suppression of CAP-sensitive bladder afferent nerves but not of bladder inflammation.