Glibenclamide attenuates myocardial injury by lipopolysaccharides in streptozotocin-induced diabetic mice.
Glibenclamide attenuates myocardial injury by lipopolysaccharides in streptozotocin-induced diabetic mice.
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DOI：
10.1186/s12933-014-0106-y
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发表时间：
2014-07-31
影响因子：
9.3
通讯作者：
Jiang GJ
中科院分区：
文献类型：
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作者：
Cai J;Lu S;Yao Z;Deng YP;Zhang LD;Yu JW;Ren GF;Shen FM;Jiang GJ
脓毒症是一种常见病，在世界范围内发病率持续上升。疾病，如糖尿病，可能使情况更糟。糖尿病患者患常见感染的风险增加。本研究旨在探讨格列本脲对脂多糖（LPS）诱导的糖尿病小鼠（STZ-小鼠）心肌损伤的作用。LPS用于诱导STZ小鼠的内毒素血症。用MPA-HBBS测定心率和平均动脉压。采用酶联免疫吸附试验（ELISA）测定血清肾上腺素水平。光镜、透射电镜及TUNEL染色观察心肌损伤情况。免疫组化法检测巨噬细胞浸润。用ELISA法测定STZ小鼠心肌组织、血清及原代培养的腹腔巨噬细胞条件培养液中白细胞介素1β（IL 1β）和肿瘤坏死因子α（TNF α）的含量。通过Western印迹分析测量Nalp 3和Caspase-1蛋白水平。STZ给药降低C57 BL/6小鼠的体重并增加血糖。LPS注射引起C57 BL/6小鼠心率和平均动脉压下降，血清肾上腺素水平升高。与对照组相比，LPS诱导的STZ-小鼠心肌损伤和巨噬细胞浸润更为严重，格列本脲预处理可减轻这种损伤。LPS刺激可使心肌组织和血清中IL-1β和TNF-α水平升高。格列本脲预处理显著抑制促炎细胞因子的血清水平。高糖或LPS均可使腹腔巨噬细胞条件培养液中IL-1β和TNF-α水平升高。格列本脲可抑制高糖和LPS诱导的IL-1β水平升高。此外，高糖加LPS显著增加Nalp 3和Caspase-1水平，格列本脲处理显著抑制这两种蛋白。结论：格列本脲可减轻LPS诱导的STZ小鼠心肌损伤，其机制可能与抑制Nalp 3炎性小体介导的炎症反应有关。本文的在线版本（doi：10.1186/s12933-014-0106-y）包含补充材料，可供授权用户使用。
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). 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. 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. 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. The online version of this article (doi:10.1186/s12933-014-0106-y) contains supplementary material, which is available to authorized users.