九肽激活肥大细胞致类过敏反应的作用及其机制  

Effects and mechanism of anaphylactoid reaction induced by nonapeptide activating mast cells

作　　者：陈晓敏 刘娜[1] 张丽娜[1] 李友佳[1] CHEN Xiaomin;LIU Na;ZHANG Lina;LI Youjia(Dept.of Pharmacy,the Second Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710004,China)

机构地区：[1]西安交通大学第二附属医院药学部,西安710004

出　　处：《中国药房》2023年第24期2995-2999,共5页China Pharmacy

基　　金：陕西省科技计划项目(No.2023-JC-QN-0805)。

摘　　要：目的探讨九肽IVQKIKHCF激活肥大细胞引发类过敏反应的作用及潜在机制。方法以人肥大细胞系LAD2为对象,以P物质为阳性对照,通过检测β-氨基己糖苷酶释放率、组胺释放量、炎症因子释放量来考察25、50、100μmol/L IVQKIKHCF的激活作用;分别以敲低MrgprX2的LAD2细胞和Mas相关G蛋白偶联受体X2(MRGPRX2)高表达的人胚胎肾细胞系HEK293(MRGPRX2/HEK293细胞)为对象,通过检测β-氨基己糖苷酶释放率和细胞内钙离子浓度来评价IVQKIKHCF激活作用与MRGPRX2的相关性。结果25、50、100μmol/L的IVQKIKHCF可显著提高LAD2细胞的β-氨基己糖苷酶释放率和组胺释放量(P<0.05),并不同程度地促进肿瘤坏死因子α、白细胞介素8、巨噬细胞炎症蛋白1β、单核细胞趋化蛋白1的释放(P<0.05);敲低MrgprX2后,25、50、100μmol/L的IVQKIKHCF对LAD2细胞β-氨基己糖苷酶释放的促进作用被显著逆转(P<0.05),且可升高MRGPRX2/HEK293细胞内的钙离子浓度。结论九肽IVQKIKHCF可通过激活MRGPRX2而促进肥大细胞释放颗粒物质和炎症介质,从而引发类过敏反应。OBJECTIVE To study the effects and potential mechanism of anaphylactoid reaction induced by nonapeptide IVQKIKHCF activating mast cells.METHODS Using human mast cell line LAD2 as subject,and substance P as positive control,the activation effects of 25,50 and 100μmol/L IVQKIKHCF on mast cells were investigated by determining the release rate ofβ-aminohexosidase,histamine release,and the contents of inflammatory factors;using MrgprX2-knockdown LAD2 cells and Masrelated G protein-coupled receptor X2(MRGPRX2)high-expression human embryonic kidney cell line HEK293(MRGPRX2/HEK293 cells)as subject,the correlation between the activation effect of IVQKIKHCF and MRGPRX2 was investigated by determining the release rate ofβ-aminohexosidase,and intracellular calcium ion concentration.RESULTS IVQKIKHCF with 25,50,100μmol/L could significantly increase the release rate ofβ-aminohexosidase and histamine release in LAD2 cells(P<0.05),and promote the release of tumor necrosis factor-α,interleukin-8,macrophage inflammatory protein-1βand monocyte chemotactic protein-1 to varying degrees(P<0.05).After knocking down MrgprX2,the effects of 25,50,100μmol/L IVQKIKHCF promoting the release ofβ-aminohexosidase in LAD2 cells were reversed significantly(P<0.05),resulting in an increase of calcium ion concentration in MRGPRX2/HEK293 cells.CONCLUSIONS Nonapeptide IVQKIKHCF can promote mast cells to release granular matter and inflammatory mediators by activating MRGPRX2 thus inducing anaphylactoid reaction.

关 键 词：九肽 IVQKIKHCF 肥大细胞 类过敏反应 Mas相关G蛋白偶联受体X2 

分 类 号：R965[医药卫生—药理学]