蝉花虫草镇痛化合物对痛风大鼠转录组及Adora1等疼痛相关基因的影响  

Effects of antinocieptive compound from Ophiocordyceps sobolifera on the transcriptome and Adora1 etc. pain-related genes in gouty rats

作　　者：朱伟坚[1,2] 柴一秋[1,2] 金轶伟[2] 厉晓腊[2] 俞晓平[1] 

机构地区：[1]中国计量大学生命科学学院浙江省生物计量及检验检疫技术重点实验室,浙江杭州310018 [2]浙江省亚热带作物研究所温州市虫生真菌资源研究与开发重点实验室,浙江温州325005

出　　处：《菌物学报》2017年第1期48-59,共12页Mycosystema

基　　金：温州市种子种苗创新项目(N20150010);温州市四新项目(F-DY201509170025);温州市公益性科技项目(N20140037)~~

摘　　要：本研究采用活性追踪的方法从蝉花虫草Ophiocordyceps sobolifera中分离提取了镇痛活性物质N^6-(2-羟乙基)腺苷[N^6-(2-hydroxyethyl)-adenosine,HEA],并通过转录组测序技术探索了HEA对痛风模型大鼠疼痛相关基因的影响。结果表明932个基因存在差异表达,将差异基因与在线疼痛基因大数据及相关文献进行比对,发现了57个疼痛相关基因,其中12个基因与镇痛相关,包括上调表达的腺苷A1受体基因(Adora1)及A2A受体基因(Adora2a)。应用Western blot的方法验证了HEA(7.5mg/kg)诱导镇痛靶标受体腺苷A1受体(A1R)表达上调、腺苷A2A受体(A2AR)表达下调。选择性A1R拮抗剂DPCPX显著抑制HEA对A1R的上调表达作用。综上所述,蝉花虫草的镇痛活性物质为HEA,而HEA可能通过激活腺苷A1R、下调A2AR及调控一系列疼痛相关基因发挥其镇痛作用。N^6-（2-hydroxyethyl）-adenosine（HEA） separated and purified from the artificial cultivation of Ophiocordyceps sobolifera was confirmed to be responsible for analgesia of acetic acid-stimulated mice. The m RNA expression of synovium from gouty rats treated with or without HEA was compared by transcriptome sequence and 932 differential expressed genes（DEGs） were obtained. Comparison of these 932 DEGs with the pain gene database, where the genes were changed during pain, 57 genes were supposed to be highly potential to participate in the regulation of pain. According to related reports, 12 antinocieptive genes were obtained including up-regulated adenosine A1 receptor（A1R, Adora1） and A2 A receptor（A2AR, Adora2a）. The result of Western blot showed that A1 R and A2 AR, the regulated target of pain, were markedly increased and decreased respectively in HEA group（7.5mg/kg） as compared with model group, and the effect of HEA on A1 R was reversed by the administration of selective A1 R antagonist DPCPX. These result demonstrated that HEA took the responsibility for the analgesia of gouty rats, and HEA may exert its antinociception by the activation of A1 R, down-regulated A2 AR and regulation of other pain-related genes.

关 键 词：N6-(2-羟乙基)腺苷 尿酸钠 腺苷A1受体 腺苷A2A受体 腺苷A1受体拮抗剂DPCPX 

分 类 号：R285.5[医药卫生—中药学]