冰片通过TRPM8减轻小鼠心肌梗死后炎症反应并抑制心脏重构  

Borneol attenuates inflammation and inhibits cardiac remodeling after myocardial infarction in mice via TRPM8

作　　者：何滢蓉 胡陶 王武帅 杨曦 段清华 杜萱 王强 HE Yingrong;HU Tao;WANG Wushuai;YANG Xi;DUAN Qinghua;DU Xuan;WANG Qiang(Clinical College of Medicine,Department of Cardiology,Southwest Medical University,Luzhou 646000,China;Department of Cardiology,The General Hospital of Western Theater Command,Chengdu 610083,China;Chengdu Medical College,Chengdu 610500,China)

机构地区：[1]西南医科大学临床医学院心血管内科,四川泸州646000 [2]西部战区总医院心血管内科,四川成都610083 [3]成都医学院,四川成都610500

出　　处：《中国病理生理杂志》2024年第3期456-464,共9页Chinese Journal of Pathophysiology

基　　金：四川省自然科学基金资助项目(No.2022NSFSC0820);国家自然科学基金资助项目(No.81500224)。

摘　　要：目的:研究冰片(borneol)对小鼠心肌梗死(myocardial infarction,MI)后炎症反应和心脏重构的作用及可能机制。方法:8周龄野生型(wild-type,WT)C57BL/6小鼠和瞬时受体电位阳离子通道M亚家族成员8(transient receptor potential cation channel subfamily M member 8,TRPM8)基因敲除(TRPM8 gene knockout,TRPM8−/−)小鼠随机分为假手术组和MI组,再分别用生理盐水(对照组)或冰片(冰片组)灌胃。绘制小鼠MI后生存曲线,28 d后超声心动图检测心脏功能,多导生理记录仪测量血流动力学参数,病理染色观察MI面积、心肌肥大和间质纤维化,并检测梗死交界区心肌中炎症反应情况。结果:在WT小鼠中,梗死交界区心肌组织中TRPM8表达显著增加(P<0.05),冰片对心脏中TRPM8表达无影响(P>0.05),但可提高小鼠生存率,缩小MI面积,抑制MI后心脏重构,改善心脏功能(P<0.05或P<0.01);在TRPM8−/−小鼠中,冰片对小鼠生存率、MI面积、心肌肥大、心肌纤维化和心脏功能未见明显影响(P>0.05)。在WT小鼠中,冰片可减少中性粒细胞和巨噬细胞的浸润(P<0.01),抑制炎症因子肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、白细胞介素1β(interleukin-1β,IL-1β)、IL-6和单核细胞趋化蛋白1(monocyte chemotactic protein-1,MCP-1)过度表达(P<0.05或P<0.01);而在TRPM8−/−小鼠中,冰片对炎症细胞数量和炎症因子表达未见明显影响(P>0.05)。结论:TRPM8可能是冰片在心脏的作用靶点;冰片可能通过TRPM8减轻MI后炎症反应和抑制心脏重构,改善小鼠MI后的心脏功能。AIM:To examine the effects of borneol on inflammation and myocardial remodeling after myocardial infarction(MI)in mice,and to investigate the underlying mechanisms.METHODS:Eight-week-old wild-type(WT)C57BL/6 mice and transient receptor potential cation channel subfamily M member 8(TRPM8)gene knockout(TRPM8−/−)mice were randomly divided into sham and MI groups,and were subsequently treated with normal saline(control group)or borneol(borneol group)via gavage.Survival curves were plotted for WT and TRPM8−/−mice with MI treated with or without borneol.After 28 d,cardiac function of the mice was assessed through echocardiography,and haemodynamic indexes were evaluated using a multi-channel physiological instrument.Infarct size,myocardial hypertrophy and interstitial fibrosis were assessed via pathological staining.In addition,inflammatory response in the peri-infarct region was detected.RE⁃SULTS:The TRPM8 expression was up-regulated in the peri-infarct region of the mice with MI(P<0.05),and borneol had no effect on TRPM8 expression(P>0.05).Borneol increased the survival rate,reduced the infarct size,inhibited cardiac remodeling and improved cardiac function in WT mice with MI(P<0.05 or P<0.01).However,it did not affect the survival rate,infarct size,myocardial hypertrophy,myocardial fibrosis or cardiac function in TRPM8−/−mice(P>0.05).Furthermore,borneol reduced inflammatory cell infiltration and the expression of inflammatory cytokines,tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),IL-6 and monocyte chemotactic protein-1(MCP-1),in WT mice(P<0.05 or P<0.01)but not in TRPM8−/−mice(P>0.05).CONCLUSION:Borneol attenuates inflammation,inhibits cardiac remodeling and improves cardiac function in mice with MI via TRPM8.

关 键 词：心肌梗死 心脏重构 冰片 瞬时受体电位阳离子通道M亚家族成员8 炎症 

分 类 号：R541.4[医药卫生—心血管疾病] R285.5[医药卫生—内科学] R363.2[医药卫生—临床医学]