Gefapixant,a Novel P2X3 Antagonist,Protects against Post Myocardial Infarction Cardiac Dysfunction and Remodeling Via Suppressing NLRP3 Inflammasome
作者机构：Department of CardiologyRenmin Hospital of Wuhan UniversityWuhan430060China Cardiovascular Research InstituteWuhan UniversityWuhan430060China Hubei Key Laboratory of CardiologyWuhan430060China Department of CardiologyWuhan No.1 HospitalWuhan Hospital of Traditional Chinese and Western MedicineWuhan430022China
出 版 物：《Current Medical Science》 (当代医学科学（英文）)
年 卷 期：2023年第43卷第1期
页 面：58-68页
核心收录：
学科分类：1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学]
基 金：supported by the National Natural Science Foundation of China(No.81370282)
主 题：myocardial infarction P2X3 inhibition gefapixant nucleotide-binding and oligomerization domain-like receptors family pyrin-domain-containing 3 inflammasome sympathetic nerve
摘 要：Objective The ATP responsive P2 purinergic receptors can be subdivided into metabotropic P2X family and ionotropic P2Y *** these,P2X3 is a type of P2X receptor which is specifically expressed on nerves,especially on pre-ganglionic sensory *** study investigates whether gefapixant possesses the potential of inhibiting cardiac sympathetic hypersensitivity to protect against cardiac remodeling in the context of myocardial *** The Sprague-Dawley rats were divided randomly into three groups:sham group-myocardial infarction group,and myocardial infarction with gefapixant treatment *** infarction was induced by left anterior descending branch *** gefapixant solution was intraperitoneally injected each time per day for 7 days and the appropriate dosage of gefapixant was determined according to the results of hematoxylin-eosin(HE)staining and myocardial injury *** of cardiac function were assessed by echocardiograph and cardiac fibrosis was evaluated by Western blotting and immunofluorescence staining of collagen I and collagen *** sympathetic innervation was detected by norepinephrine concentration(pg/mL),in-vivo electrophysiology,and typical sympathetic *** cell infiltration was shown from immunofluorescence staining and pro-inflammatory signaling pathway activation was checked by immunohistology,quantitative realtime PCR(qPCR)and Western *** It was found that gefapixant injection of 10 mg/kg per day had the highest dosage-efficacy ***,gefapixant treatment improved cardiac pump function as shown by increased LVEF and LVFS,and decreased LVIDd and *** expression levels of collagen I and collagen III,and TNF-αwere all decreased by P2X3 ***,the decreased activation of nucleotide-binding and oligomerization domain-like receptors family pyrin-domain-containing 3(NLRP3)inflammasome and subsequent cleavage of caspase-1 which modula
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