title: Glibenclamide attenuates myocardial injury by lipopolysaccharides in streptozotocin-induced diabetic mice.
abstract: BACKGROUND
  Sepsis is a common disease that continues to increase in incidence in the world. Diseases, such as diabetes mellitus, may make the situation worse. Diabetic patients are at increased risk for common infections. This study was designed to investigate the role of glibenclamide on myocardial injury by lipopolysaccharides (LPS) in streptozotocin induced diabetic mice (STZ-mice).
  
  
  METHODS
  LPS was used to induce endotoxemia in STZ-mice. Heart rate and mean arterial pressure were measured by MPA-HBBS. Serum epinephrine level was measured by enzyme-linked immunosorbent assays (ELISA). Myocardial injury was examined by light and transmission electron microscope and TUNEL staining. Macrophage infiltration was measured by immunohistochemistry. Interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) levels in myocardial tissue and serum in STZ-mice, and in conditional medium of primary cultured peritoneal macrophages were determined by ELISA. Nalp3 and Caspase-1 protein levels were measured by Western blotting analysis.
  
  
  RESULTS
  STZ administration decreased body weight and increased blood glucose in C57BL/6 mice. LPS injection caused decreases of heart rate and mean arterial pressure, and elevated serum epinephrine level in C57BL/6 mice. Compared with control mice without STZ treatment, LPS induced more severe myocardial injury and macrophage infiltration in STZ-mice, which was attenuated by pretreatment of glibenclamide. LPS stimulation enhanced the levels of IL-1β and TNF-α in both cardiac tissue and serum. Glibenclamide pretreatment significantly inhibited the serum levels of pro-inflammatory cytokines. Either high glucose or LPS increased the levels of IL-1β and TNF-α in the conditional medium of peritoneal macrophages. Glibenclamide treatment suppressed the increase of IL-1β level induced by high glucose and LPS. Furthermore, Nalp3 and Caspase-1 levels were markedly increased by high glucose plus LPS, and both proteins were significantly inhibited by glibenclamide treatment.
  
  
  CONCLUSIONS
  We conclude that glibenclamide could attenuate myocardial injury induced by LPS challenge in STZ-mice, which was possibly related to inhibiting inflammation through Nalp3 inflammasomes.
authors: Jian
authors: J
authors: Cai
authors: Shuai
authors: S
authors: Lu
authors: Zheng
authors: Z
authors: Yao
authors: Ya-Ping
authors: YP
authors: Deng
authors: Ling-Di
authors: LD
authors: Zhang
authors: Jia-Wen
authors: JW
authors: Yu
authors: Guo-Fei
authors: GF
authors: Ren
authors: Department of Pharmacy, Zhejiang Xiaoshan Hospital, Hangzhou 311202, Zhejiang, China. fumingshen@hotmail.com.
authors: Fu-Ming
authors: FM
authors: Shen
authors: Guo-Jun
authors: GJ
authors: Jiang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000473:pathology; D019446:Endotoxemia / Q000139:chemically induced / Q000473:pathology; D005905:Glyburide / Q000627:therapeutic use*; D006335:Heart Injuries / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018805:Sepsis / Q000139:chemically induced
chemical_list: D007004:Hypoglycemic Agents; D008070:Lipopolysaccharides; D005905:Glyburide