title: Gene silencing of non-obese diabetic receptor family (NLRP3) protects against the sepsis-induced hyper-bile acidaemia in a rat model.
abstract: The role of NOD-like receptor family (NLRP3) has been confirmed in various inflammatory diseases. The association between NLRP3 and hyper-bileacidaemia during the sepsis remains unclear. We aimed to investigate whether NLRP3 silencing protects against the sepsis-induced hyper-bileacidaemia. Sepsis was induced by caecum ligation and puncture (CLP). Gene silencing of NLRP3 was performed by injecting rats with NLRP3 short hairpin RNA plasmids (NLRP3 shRNA) 48 h before surgery. Rats were divided into four groups: group 1: sham; group 2: sepsis; group 3: NLRP3 shRNA + sepsis (called the 'NLRP3 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 NLRP3 expression was increased dramatically during the sepsis, but was suppressed by pretreatment with NLRP3 shRNA. Compared with rats in the sepsis and the scrambled shRNA groups, rats in the NLRP3 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 NLRP3 ameliorates sepsis-induced hyper-bileacidaemia by rehabilitating hepatocyte transporter expression, reducing hepatic cytokine levels, neutrophil infiltration and macrophages pyroptosis. NLRP3 may be a pivotal target for sepsis management.
authors.affiliation: Department of Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Wu
authors.forename: J
authors.initials: J
authors.lastname: Ren
authors.forename: B
authors.initials: B
authors.lastname: Zhou
authors.forename: C
authors.initials: C
authors.lastname: Ding
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.forename: G
authors.initials: G
authors.lastname: Wang
authors.forename: G
authors.initials: G
authors.lastname: Gu
authors.forename: X
authors.initials: X
authors.lastname: Wu
authors.forename: S
authors.initials: S
authors.lastname: Liu
authors.forename: D
authors.initials: D
authors.lastname: Hu
authors.forename: J
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000097:blood / Q000235:genetics; D002352:Carrier Proteins; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D020868:Gene Silencing; D005998:Glycine / Q000097:blood / Q000235:genetics; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D006932:Hyperbilirubinemia / Q000097:blood* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D020556:Neutrophil Infiltration / Q000235:genetics; D009504:Neutrophils / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear; D018805:Sepsis / Q000097:blood* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D013654:Taurine / Q000097:blood / Q000235:genetics
chemical_list: D001647:Bile Acids and Salts; D002352:Carrier Proteins; D016207:Cytokines; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C573346:Nlrp3 protein, rat; D018160:Receptors, Cytoplasmic and Nuclear; D013654:Taurine; D005998:Glycine
keywords: NLRP3 inflammasome; hyper-bileacidaemia; liver injury; sepsis