Changes of endothelin-1 gene expression in rat brains during ischemia and ischemic reperfusion

The experiment was designed to study the association of cerebral ischemia and reperfusion with endothelin-1 (ET-1) gene expression of rat brains and time-dependent changes of ET-1 gene expression during cerebral ischemia.

Thirty-three male SD rats were divided into dot blot hybridization (n = 27) and in situ hybridization groups (n = 6). The focal cerebral ischemia and reperfusion models were made with suture embolism of middle cerebral artery. Dot blot hybridization groups were redivided into control and ischemic subgroups (ischemia for 0.5, 1, 1.5, 3, 6, 12, 24, 48 and 72 h respectively). In situ hybridization groups were redivided into ischemia and reperfusion groups. After 24 h ischemia and 24 h reperfusion, ET-1 gene expressions were investigated with in situ hybridization and the results were analyzed with IBAS 2000 Image Analysis System.

Dot blot hybridization showed that ET-1 mRNA of cerebral cortex and caudate-putamen was increased at 6 h of ischemia and reached peak at 24 h (3.9 and 3.7 fold respectively), and at 72 h of ischemia it remained at high levels (3.5 and 2.1 fold respectively). In situ hybridization showed that the levels of ET-1 mRNA of cerebral cortex and caudate-putamen were also markedly increased both in 24 h ischemia and 24 h reperfusion groups (P < 0.01, P < 0.05 respectively).

ET-1 gene expression in focal ischemic brain tissue were markedly and progressively increased during cerebral ischemia and reperfusion and down-regulation of ET-1 gene expression may be a new approach to the treatment of ischemic cerebrovascular diseases.