组胺H1受体缺乏改变小鼠脑内组胺含量及昼夜节律

在乙谜麻醉下,分别于明时(8:00 a.m.)及暗时(8:00 p.m.)断头处死野生型及组胺H1R基因敲除型小鼠,迅速取出脑组织并分离出皮层、纹状体、海马、下丘脑、丘脑、中脑及脑干等脑区.这些脑组织被制成匀浆并用HPLC荧光检测法测量其组胺含量.结果显示暗时处死时,H1R基因敲除型小鼠海马、丘脑、中脑及脑干中的组胺含量明显低于野生型小鼠.明时处死时,野生型小鼠各脑区组胺含量均较暗时处死显著降低,但这一变化在H1R基因敲除型小鼠中并未观察到.这些表明作为组胺的功能靶,H1R不仅介导组胺的功能,而且调节大脑中组胺含量与释放的昼夜节律.

HISTAMINE H1 RECEPTOR DEFICIENCY ALTERS BRAIN HISTAMINE CONTENTS AND CIRCADIAN RHYTHM IN MICE

Under anesthesia by diethyl ether, histamine H1 receptor (H1R) gene knockout (KO) and wild-type (WT) mice were killed by decapitation either at 8:00 p.m. or at 8:00 a.m. The brains were quickly removed out and divided on ice into seven regions: the cortex, striatum, hippocampus, hypothalamus, thalamus, midbrain and medulla. These brain regions were homogenized and the histamine content in the homogenate was determined by HPLC- fluorometry. The results showed that at 8:00 p.m. histamine contents in the hippocampus, thalamus, midbrain, and medulla of DPR-KO mice were significantly decreased compared with WT mice (P<0.05). In WT mice, histamine contents in almost all brain regions were markedly higher at 8:00 p.m. than at 8:00 a.m, whereas the difference was not observed in H1R KO mice. We conclude that as the function target of histamine, H1R not only modulates the function of histamine, but also regulates the histamine content and its synthesizing or releasing rhythm in the mouse brain.