J Anesth Perioper Med. 2014;1(1):36-43. https://doi.org/10.24015/ebcmed.japm.2014.0006

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, and Jian-Jun Yang

From the Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.

Correspondence to Jian-Jun Yang at yjyangjj@126.com.

EBCMED ID: ebcmed.japm.2014.0006 DOI: 10.24015/ebcmed.japm.2014.0006


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 in fl ammasome. However, the role of glibenclamide on acute lung injury (ALI) is not known in a mouse model induced by cecal ligation and perforation (CLP).

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-todry 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.

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.

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

Article Type
Original Article

Declaration of Interests
All authors have no financial support and potential conflicts of interest for this work.

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