Original Research

Glibenclamide Pretreatment Attenuates Acute Lung Injury by Inhibiting the Inflammatory Responses and Oxidative Stress in a Polymicrobial Sepsis Animal Model

Mu-Huo Ji , Jiao-Jiao Yang , Lin-Sha Ju , Si-Hai Zhu , Jian-Jun Yang
Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
J Anesth Perioper Med 2014; 1(1): 36- 43 . Published on Sep 9, 2014 . doi:10.24015/JAPM.2014.0006
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Abstract

Background: Emerging evidence suggests that the NLRP3 inflammasome pathway and its downstream cytokines play key roles in the pathophysiology of inflammatory diseases. Glibenclamide is a widely used sulfonylurea drug for the treatment of type 2 diabetes, which has been reported to inhibit the activation of NLRP3 inflammasome. However, the role of glibenclamide on acute lung injury (ALI) is not known in a mouse model induced by cecal ligation and perforation (CLP). 

Methods: Thirty mice were equally assigned to the Sham group, CLP group, and CLP+glibenclamide groups (N=10). One hour before CLP or sham operation, mice received an intraperitoneal injection of 50 mg/kg glibenclamide or the same volume of normal saline. Interleukin (IL)-1β, IL-6, IL-18, tumor necrosis factor (TNF)-α, Toll-like receptor 4, inducible nitric oxide synthase, caspase-1, nitric oxide, wet-to-dry weight ratio, malondialdehyde, and superoxide dismutase in the lung were assessed at 24 hours after the operation. The 7-day survival rate was also recorded.

Results: Glibenclamide pretreatment alleviated ALI, as indicated by decreased neutrophil infiltration and wet-to-dry weight ratio, which was accompanied by the decreased levels of interleukin (IL)-1β, IL-6, Toll-like receptor 4, inducible nitric oxide synthase, caspase-1, nitric oxide, and malondialdehyde in the lung. Furthermore, glibenclamide pretreatment prevented the sepsis-induced hyperglycemia at 6 hours after CLP. However, no significant difference was detected in pulmonary levels of nuclear factor (NF)-κB p65, TNF-α, IL-18, and superoxide dismutase or the 7-day survival rate between the CLP group and the CLP + glibenclamide group. 

Conclusions: Glibenclamide pretreatment attenuates the ALI by inhibiting the inflammatory responses and oxidative stress in a polymicrobial sepsis animal model.

 

Citation: Mu- Huo Ji, Jiao- Jiao Yang, Lin- Sha Ju, Si- Hai Zhu, Jian- Jun Yang. Glibenclamide pretreatment attenuates acute lung injury by inhibiting the inflammatory responses and oxidative stress in a polymicrobial sepsis animal model. J Anesth Perioper Med 2014; 1: 36-43. doi: 10.24015/JAPM.2014.0006

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