Gene silencing of non‐obese diabetic receptor family ( NLRP 3) protects against the sepsis‐induced hyper‐bile acidaemia in a rat model

Summary The role of NOD ‐like receptor family ( NLRP 3) has been confirmed in various inflammatory diseases. The association between NLRP 3 and hyper‐bileacidaemia during the sepsis remains unclear. We aimed to investigate whether NLRP 3 silencing protects against the sepsis‐induced hyper‐bileacidaemia. Sepsis was induced by caecum ligation and puncture ( CLP ). Gene silencing of NLRP 3 was performed by injecting rats with NLRP 3 short hairpin RNA plasmids ( NLRP 3 shRNA ) 48 h before surgery. Rats were divided into four groups: group 1: sham; group 2: sepsis; group 3: NLRP 3 shRNA  + sepsis (called the ‘ NLRP 3 shRNA ’ group); and group 4: scrambled shRNA  + sepsis (called the ‘scrambled shRNA ’ group). The serum levels of bile acids, hepatic expression of hepatocyte membrane transporters, hepatic cytokine levels and behaviours of immune cells were compared among the groups. Hepatic NLRP 3 expression was increased dramatically during the sepsis, but was suppressed by pretreatment with NLRP 3 shRNA . Compared with rats in the sepsis and the scrambled shRNA groups, rats in the NLRP 3 shRNA group exhibited significantly decreased serum levels of glycine and taurine conjugated‐bile acids, with rehabilitated expression of hepatocyte transporters, suppressed hepatic cytokine levels, decreased hepatic neutrophils infiltration and attenuated macrophages pyroptosis. Gene silencing of NLRP 3 ameliorates sepsis‐induced hyper‐bileacidaemia by rehabilitating hepatocyte transporter expression, reducing hepatic cytokine levels, neutrophil infiltration and macrophages pyroptosis. NLRP 3 may be a pivotal target for sepsis management.