Rho kinase inhibitor fasudil protect neurons in hippocampal CA1 region following cerebral ischemia reperfusion through inhibiting MLK3-JNK signal transduction pathway in rats / 国际脑血管病杂志

ABSTRACT

Objective To investigate the effect of Rho kinase inhibitor fasudil on taxed lineage kinase 3 (MLK3), c-Jun NH2-terminal kinase (JNK) phosphorylation, caspase-3expression, and neuronal injury in hippocampal CA1 region follwong cerebral ischemic rep erfusion in rats. Methods A total of 72 Sprague-Dawley rats were randomly divided into sham operation, ischemia-reperfusion, normal saline, and fasudil groups. A global cerebral ischemic model was prepared by four-vessel ligation. The levels of MLK3 and JNK phosphorylation, and caspase-3 expression were detected by Western blot analysis. Cresy1 violet staining was used to detect the numbers of survival neurons in hippocampal CA1 region. Results When 6 hours after ischemia-reperfusion, the level of MLK3 phosphorylation in the fasudil group (1.13 ± 0. 03)was significantly lower than that in the normal saline group (2. 08 ± 0. 01 ,P = 0. 000 3), while the levels of MLK3 was no significant difference. When 3 hours after ischemia-reperfusion, the level of JNK phosphorylation in the fasudil group (1.27 ±0. 02)was significantly lower than that in the normal saline group (2.09 ±0. 01, P=0. 000 2), while the levels of JNK was no significant difference. When 6 hours after ischemia-reperfusion, the expression level of caspase-3in the fasudil group (1.28 ± 0. 02) was significantly lower than that in the normal saline group (2. 10 ± 0. 01, P = 0. 000 6). When 5 days after ischemia-reperfusion, the pyramidal cells in hippocampal CA1 region almost completely disappeared in the ischemia-reperfusion group, and only a few cells left (9. 8 ±2. 1). The numbers of survival pyramidal cell (8. 28 ± 3.2) in hippocampal CA1 region in the fasudil group was significantly more than that in the normal saline group (11.8 ± 1.6, P ＜0. 05). Conclusions Fasudil may significantly inhibit the ischemia-reperfusion-induced phosphorylation of MLK3 and JNK, as well as the expression of caspase-3, and thus reduce neuronal injury in hippocampal CA1 region.