ヒスタミンH2受容体作用薬amthamineによる頭部外傷後の脳血管障害に対する抑制作用

• Published in: 日本薬理学会年会要旨集 p. 1-O-C2-4
• Main Authors: 園田, 清美, 稲月, 直樹, 道永, 昌太郎, 綿野, 智一, 水口, 博之
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2021
• Subjects: histamine
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.94.0_1-O-C2-4

Histamine is a major neurotransmitter for regulation of neuronal and vascular functions. Several studies found that histamine H2 receptor agonists alleviated neuronal damage after brain injury. In this study, we investigated the effects of amthamine, a selective H2 receptor agonist for cerebrovascular damage after traumatic brain injury (TBI). To prepare TBI model, mice (male ddY, 7 weeks) were given a fluid percussion injury (FPI) by hydraulic impact on the dura mater. The cerebrovascular damage was evaluated by Evans blue extravasation in mouse cerebrum. Amthamine (20-500 nmol/day) was administrated into lateral cerebroventricle from 3 hours to 3 days after FPI. Expressions of histamine H2 receptor were evaluated by western blot and immunohistochemistry. Expressions of mRNAs for angiopoietin-1 (ANG-1) and sonic hedgehog (SHH), vascular protective factors were determined by Real-time PCR. The administrations of amthamine alleviated the Evans blue extravasation after FPI. Moreover, amthamine accelerated mRNA expressions of ANG-1 and SHH in mouse cerebrum. Expressions of histamine H2 receptor were observed in astrocytes and brain endothelial cells. Amthamine (2-200 mM) promoted ANG-1 and SHH productions in cultured astrocytes, and increased ANG-1 expression in bEnd.3 cells (brain endothelial cells). These results suggest that histamine H2 receptor agonist alleviates TBI-induced cerebrovascular damage by increase of vascular protective factors.