We investigated the role of the nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome during testis ischemia and reperfusion injury (TI/R) in wild-type (WT) and NLRP3 knock-out (KO) mice. WT and KO mice underwent 1 hour testicular ischemia followed by 4 hours and 1 and 7 days of reperfusion or a sham TI/R. Furthermore， two groups of WT mice were treated at the beginning of reperfusion and up to 7 days with two inflammasome inhibitors， BAY 11-7082 (20 mg/kg i.p.) or Brilliant Blue G (45.5 mg/kg i.p.)， or vehicle. Animals were killed with a pentobarbital sodium overdose at 4 hours and 1 and 7 days， and bilateral orchidectomies were performed. B... More
We investigated the role of the nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome during testis ischemia and reperfusion injury (TI/R) in wild-type (WT) and NLRP3 knock-out (KO) mice. WT and KO mice underwent 1 hour testicular ischemia followed by 4 hours and 1 and 7 days of reperfusion or a sham TI/R. Furthermore， two groups of WT mice were treated at the beginning of reperfusion and up to 7 days with two inflammasome inhibitors， BAY 11-7082 (20 mg/kg i.p.) or Brilliant Blue G (45.5 mg/kg i.p.)， or vehicle. Animals were killed with a pentobarbital sodium overdose at 4 hours and 1 and 7 days， and bilateral orchidectomies were performed. Biochemical and morphologic studies were carried out in all groups. TI/R in WT mice significantly increased caspase-1 and interleukin (IL)-1β mRNA after 4 hours and IL-18 mRNA at 1 day of reperfusion (P ≤ 0.05). There was also a significant increase in caspase-3 and terminal deoxynucleotidyl transferase-mediated digoxigenin-deoxyuridine nick-end labeling-positive cells， marked histologic damage， and altered spermatogenesis in WT mice in both testes after 1 and 7 days of reperfusion. KO TI/R mice， WT TI/R BAY 11-7082， and Brilliant Blue G treated mice showed a significant reduced IL-1β and IL-18 mRNA expression， blunted caspase-1 and -3 expression， minor histologic damages， low terminal deoxynucleotidyl transferase-mediated digoxigenin-deoxyuridine nick-end labeling activity， and preserved spermatogenesis. These data suggest that the activation of NLRP3 plays a key role in TI/R， and its inhibition might represent a therapeutic target for the management of patients with unilateral testicular torsion.
