Glibenclamide alleviates β adrenergic receptor activation-induced cardiac inflammation

被引:0
|
作者
Ning Cao
Jing-jing Wang
Ji-min Wu
Wen-li Xu
Rui Wang
Xian-da Chen
Ye-nan Feng
Wen-wen Cong
You-yi Zhang
Han Xiao
Er-dan Dong
机构
[1] Peking University Third Hospital; NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides; Key Laboratory of Molecular Cardiovascular Science,Department of Cardiology and Institute of Vascular Medicine
[2] Ministry of Education; Beijing Key Laboratory of Cardiovascular Receptors Research,Intensive Care Unit, Emergency Medical Research Institute
[3] Tianjin First Center Hospital,Ministry
[4] Shihezi University,of
来源
Acta Pharmacologica Sinica | 2022年 / 43卷
关键词
glibenclamide; cardiac inflammation; isoprenaline; sympathetic stress; NLRP3 inflammasome; adrenergic receptor;
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学科分类号
摘要
β-Adrenergic receptor (β-AR) overactivation is a major pathological factor associated with cardiac diseases and mediates cardiac inflammatory injury. Glibenclamide has shown anti-inflammatory effects in previous research. However, it is unclear whether and how glibenclamide can alleviate cardiac inflammatory injury induced by β-AR overactivation. In the present study, male C57BL/6J mice were treated with or without the β-AR agonist isoprenaline (ISO) with or without glibenclamide pretreatment. The results indicated that glibenclamide alleviated ISO-induced macrophage infiltration in the heart, as determined by Mac-3 staining. Consistent with this finding, glibenclamide also inhibited ISO-induced chemokines and proinflammatory cytokines expression in the heart. Moreover, glibenclamide inhibited ISO-induced cardiac fibrosis and dysfunction in mice. To reveal the protective mechanism of glibenclamide, the NLRP3 inflammasome was further analysed. ISO activated the NLRP3 inflammasome in both cardiomyocytes and mouse hearts, but this effect was alleviated by glibenclamide pretreatment. Furthermore, in cardiomyocytes, ISO increased the efflux of potassium and the generation of ROS, which are recognized as activators of the NLRP3 inflammasome. The ISO-induced increases in these processes were inhibited by glibenclamide pretreatment. Moreover, glibenclamide inhibited the cAMP/PKA signalling pathway, which is downstream of β-AR, by increasing phosphodiesterase activity in mouse hearts and cardiomyocytes. In conclusion, glibenclamide alleviates β-AR overactivation-induced cardiac inflammation by inhibiting the NLRP3 inflammasome. The underlying mechanism involves glibenclamide-mediated suppression of potassium efflux and ROS generation by inhibiting the cAMP/PKA pathway.
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页码:1243 / 1250
页数:7
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