title: RAGE deficiency attenuates the protective effect of Lidocaine against sepsis-induced acute lung injury.
abstract: Lidocaine (Lido) is reported to suppress inflammatory responses and exhibit a therapeutic effect in models of cecal ligation and puncture (CLP)-induced acute lung injury (ALI). The receptor for advanced glycation end product (RAGE) exerts pro-inflammatory effects by enhancing pro-inflammatory cytokine production. However, the precise mechanism by which Lido confers protection against ALI is not clear. ALI was induced in RAGE WT and RAGE knockout (KO) rats using cecal ligation and puncture (CLP) operations for 24 h. The results showed that Lido significantly inhibited CLP-induced lung inflammation and histopathological lung injury. Furthermore, Lido significantly reduced CLP-induced upregulation of HMGB1 and RAGE expression and activation of the NF-κB and MAPK signaling pathways. With the use of RAGE KO rats, we demonstrate here that RAGE deficiency attenuates the protective effect of Lido against CLP-induced lung inflammatory cell infiltration and histopathological lung injury. These results suggest that RAGE deficiency attenuates the protective effect of Lido against CLP-induced ALI by attenuating the pro-inflammatory cytokines production.
authors.affiliation: Department of Pharmacology, Pharmacy College of Southwest Medical University, Luzhou, Sichuan, China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Traditional Chinese Pharmacology, Pharmacy College of Southwest Medical University, Luzhou, Sichuan, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Anesthesiology, the First Affiliated Hospital of Southwest Medical University, No.319 Zhongshan Road, Luzhou, Sichuan, China.
authors.forename: Changli
authors.initials: C
authors.lastname: Liao
authors.affiliation: Department of Pharmacology, Pharmacy College of Southwest Medical University, Luzhou, Sichuan, China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Pharmacy College of Southwest Medical University, Luzhou, Sichuan, China.
authors.forename: Minghua
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Pharmacy College of Southwest Medical University, Luzhou, Sichuan, China.
authors.forename: Daqiang
authors.initials: D
authors.lastname: Song
authors.affiliation: Department of Anesthesiology, the First Affiliated Hospital of Southwest Medical University, No.319 Zhongshan Road, Luzhou, Sichuan, China. xianjiang2012@outlook.com.
authors.forename: Xian
authors.initials: X
authors.lastname: Jiang
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000209:etiology; D000818:Animals; D055786:Gene Knockout Techniques; D024243:HMGB1 Protein / Q000378:metabolism; D007249:Inflammation; D008012:Lidocaine / Q000494:pharmacology* / Q000627:therapeutic use; D020935:MAP Kinase Signaling System / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D000067759:Receptor for Advanced Glycation End Products / Q000172:deficiency*; D018805:Sepsis / Q000150:complications*
chemical_list: C000593874:Ager protein, rat; D024243:HMGB1 Protein; D016328:NF-kappa B; D020011:Protective Agents; D000067759:Receptor for Advanced Glycation End Products; D008012:Lidocaine
keywords: ALI; CLP; HMGB1; Lidocaine; RAGE