P物质的表达减少减轻A2腺苷受体基因敲除小鼠心肌梗死后的神经病理性疼痛  

The reduction of substance P expression alleviates neuropathic pain after myocardial infarction in A2 adenosine receptor knockout mice

作　　者：曾小林 王艳[2] 卢加发 李海鹰 韩伟 ZENG Xiaolin;WANG Yan;LU Jiafa;LI Haiying;HAN Wei(Cardiovascular Department,Shenzhen University General Hospital,Shenzhen 518055,China;Cardiovascular Department,the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,Wenzhou 325027,China;Emergency Department,Shenzhen University General Hospital,Shenzhen 518055,China)

机构地区：[1]深圳大学总医院心血管内科,广东深圳518055 [2]温州医科大学附属第二医院心血管内科,浙江温州325027 [3]深圳大学总医院急诊科,广东深圳518055

出　　处：《中华灾害救援医学》2021年第8期1141-1145,1200,共6页Chinese Journal of Disaster Medicine

基　　金：深圳市医疗卫生三名工程资助项目(SZSM201911007);急救与创伤研究教育部重点实验室(海南医学院)开放课题基金(Grant.KLET-201905)。

摘　　要：目的研究腺苷A2A受体和P物质在小鼠急性心肌梗死中的作用和相互关系,同时验证神经源性疼痛假说,以明确阻断腺苷A2A受体,是否可以阻断心肌梗死疼痛介质P物质的过度表达和P物质受体神经激肽1(Neurokinin-1,NK-1),是否有心肌保护作用。方法健康野生型C57BL/6J(WT)小鼠36只,腺苷A2A受体敲除(KO)小鼠24只,随机分为假手术组、WT+NS组、WT+SP组、KO+NS组、KO+SP组,每组12只。结扎小鼠冠状动脉前降支建立急性心肌梗死模型,记录术前、术后心电图及超声心动图,ELISA试剂盒测定心肌组织IL-1水平的表达;实时定量RT-PCR检测急性心肌梗死心肌中P物质的表达;用福尔马林试验间接评价小鼠心肌梗死后疼痛的程度。结果P物质的RT-PCR法定量结果提示:在腺苷A2A基因敲除小鼠组,梗死心肌P物质表达量与野生型小鼠组比较明显下降(P<0.001);使用P物质受体神经激肽1阻断剂L-703606后,腺苷A2A基因敲除小鼠福尔马林试验II相期间舔足次数与野生型小鼠组比较减少(P<0.05)。结论腺苷A2A和P物质参与了心肌梗死的病理生理过程,阻断腺苷A2A受体和P物质受体神经激肽1的过度激活可降低心绞痛的程度,可能有心肌保护作用。Objective To study the roles of and relationship between adenosine A2A receptor and substance P in acute myocardial infarction in mice and to verify the hypothesis of neuropathic pain,so as to determine whether blocking adenosine A2A receptor could block the overexpression of substance P and its receptor neurokinin-1(NK-1),and contribute to myocardial protection.Methods A total of 36 healthy C57BL/6J(WT)mice and 24 mice with adenosine A2A receptor knockout(KO)were randomly divided into sham group,WT+NS group,WT+SP group,KO+NS group,and KO+SP group,with 12 mice each.The acute myocardial infarction model was established by ligating the anterior descending branch of the coronary artery in mice;Preop and postop ECG and echocardiogram were recorded;The express level of IL-1 in mouse myocardial tissue was evaluated using ELISA;The expression of substance P was detected by real-time quantitative RT-PCR;Formalin test was used to indirectly evaluate the degree of pain after myocardial infarction in mice.Results Compared with wild-type mice,the expression of substance P was significantly decreased in adenosine A2A knockout mice(P<0.001);After using substance P receptor neurokinin-1 blocker L-703606,the number of licking feet in adenosine A2A knockout mice during phase II of formalin test was decreased compared with that in wild-type mice(P<0.05).Conclusion Adenosine A2A and substance P participate in the pathophysiological process of myocardial infarction.Blocking the over activation of adenosine A2A receptor and substance P receptor neurokinin-1 can reduce the degree of angina pectoris,which may have myocardial protection.

关 键 词：腺苷A2A受体 P物质 急性心肌梗死 神经源性疼痛 疼痛机制 

分 类 号：R541.4[医药卫生—心血管疾病]