大鼠大脑中动脉短暂和永久性闭塞后环氧合酶-2信使核糖核酸的诱导：通过原位杂交与c-fos信使核糖核酸的比较

Induction of cyclooxygenase-2 messenger RNA after transient and permanent middle cerebral artery occlusion in rats: comparison with c-fos messenger RNA by using in situ hybridization.

作者信息

Kinouchi H, Huang H, Arai S, Mizoi K, Yoshimoto T

机构信息

Department of Neurosurgery, Tohoku University School of Medicine, Sendai, Japan.

出版信息

J Neurosurg. 1999 Dec;91(6):1005-12. doi: 10.3171/jns.1999.91.6.1005.

DOI:10.3171/jns.1999.91.6.1005

PMID:10584847

Abstract

OBJECT

Recently, two different cyclooxygenase (COX) genes, COX-1 and -2, were identified. In this study, topographic and chronological profiles of COX-2 messenger (m)RNA and c-fos mRNA expression were investigated using in situ hybridization after focal cerebral ischemia.

METHODS

Rats undergoing permanent ischemia were decapitated at 30 and 90 minutes and at 2, 4, 8, and 24 hours after middle cerebral artery (MCA) occlusion, and rats undergoing transient ischemia were decapitated at 4, 8, and 24 hours after MCA occlusion that lasted for either 30 or 90 minutes. After brief transient MCA occlusion, c-fos mRNA was induced in the whole MCA territory, adjacent cortex (cingulate cortex), and distant brain regions such as the hippocampus and substantia nigra. In contrast, COX-2 mRNA was not induced in the ischemic core (lateral striatum) but only in the penumbral area (MCA cortex). Long transient and permanent MCA occlusion did not induce c-fos and COX-2 mRNAs in the ischemic core but strongly induced both mRNAs in the penumbral area (medial striatum and periphery of MCA cortex) and adjacent cortex (cingulate cortex). In brain regions distant from the ischemic territory, although c-fos mRNA was induced in the thalamus, substantia nigra, and hippocampus after extended transient and permanent occlusion, COX-2 mRNA was only induced in the bilateral hippocampi. The induction of COX-2 mRNA persisted in all locations even at 24 hours after MCA occlusion.

CONCLUSIONS

The distribution of COX-2 mRNA induction was apparently different from that of c-fos mRNA after MCA occlusion. These results pertaining to COX-2 mRNA agree well with the previous observations of changes in prostaglandin metabolism induced by focal cerebral ischemia. However, whether this induction of the COX-2 gene contributes to the histopathological outcome of cerebral ischemia remains to be elucidated.

摘要

目的

最近，人们鉴定出了两种不同的环氧化酶（COX）基因，即COX-1和COX-2。在本研究中，采用原位杂交技术，对局灶性脑缺血后COX-2信使核糖核酸（mRNA）和c-fos mRNA表达的地形学和时间进程进行了研究。

方法

永久性缺血大鼠在大脑中动脉（MCA）闭塞后30分钟和90分钟以及2、4、8和24小时断头，短暂性缺血大鼠在MCA闭塞持续30或90分钟后的4、8和24小时断头。短暂性MCA短暂闭塞后，c-fos mRNA在整个MCA区域、相邻皮质（扣带回皮质）以及海马和黑质等远处脑区被诱导。相比之下，COX-2 mRNA在缺血核心区（外侧纹状体）未被诱导，仅在半暗带区域（MCA皮质）被诱导。长时间短暂性和永久性MCA闭塞在缺血核心区未诱导c-fos和COX-2 mRNA，但在半暗带区域（内侧纹状体和MCA皮质周边）和相邻皮质（扣带回皮质）强烈诱导了这两种mRNA。在远离缺血区域的脑区，尽管在长时间短暂性和永久性闭塞后丘脑、黑质和海马中诱导了c-fos mRNA，但COX-2 mRNA仅在双侧海马中被诱导。即使在MCA闭塞24小时后，COX-2 mRNA的诱导在所有部位持续存在。