西安交通大学第二附属医院药学部,西安 710004
Received:04 July 2023,
Revised:2023-10-24,
Accepted:01 November 2023,
Published:30 December 2023
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陈晓敏,刘娜,张丽娜,等.九肽激活肥大细胞致类过敏反应的作用及其机制 [J].中国药房,2023,34(24):2995-2999.
CHEN Xiaomin,LIU Na,ZHANG Lina,et al.Effects and mechanism of anaphylactoid reaction induced by nonapeptide activating mast cells[J].ZHONGGUO YAOFANG,2023,34(24):2995-2999.
陈晓敏,刘娜,张丽娜,等.九肽激活肥大细胞致类过敏反应的作用及其机制 [J].中国药房,2023,34(24):2995-2999. DOI: 10.6039/j.issn.1001-0408.2023.24.07.
CHEN Xiaomin,LIU Na,ZHANG Lina,et al.Effects and mechanism of anaphylactoid reaction induced by nonapeptide activating mast cells[J].ZHONGGUO YAOFANG,2023,34(24):2995-2999. DOI: 10.6039/j.issn.1001-0408.2023.24.07.
目的
2
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
2
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、100 μmol/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
2
25、50、100 μmol/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、100 μmol/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
2
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
2
To study the effects and potential mechanism of anaphylactoid reaction induced by nonapeptide IVQKIKHCF activating mast cells.
METHODS
2
Using human mast cell line LAD2 as subject, and substance P as positive control, the activation effects of 25, 50 and 100 μmol/L IVQKIKHCF on mast cells were investigated by determining the release rate of
β
-aminohexosidase, histamine release, and the contents of inflammatory factors; using
MrgprX2
-knockdown LAD2 cells and Mas
-related 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 of
β
-aminohexosidase, and intracellular calcium ion concentration.
RESULTS
2
IVQKIKHCF with 25, 50, 100 μmol/L could significantly increase the release rate of
β
-aminohexosidase and histamine release in LAD2 cells (
P
<0.05), and promote the release of tumor necrosis factor-α, interleukin-8, macrophage inflammatory protein-1β and monocyte chemotactic protein-1 to varying degrees (
P
<0.05). After knocking down
MrgprX2
, the effects of 25, 50, 100 μmol/L IVQKIKHCF promoting the release of
β
-aminohexosidase in LAD2 cells were reversed significantly (
P
<0.05), resulting in an increase of calcium ion concentration in MRGPRX2/HEK293 cells.
CONCLUSIONS
2
Nonapeptide IVQKIKHCF can promote mast cells to release granular matter and inflammatory mediators by activating MRGPRX2 thus inducing anaphylactoid reaction.
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