Effects of a Rho kinase inhibitor fasudil hydrochloride on GluR6 and neuronal apoptosis in cerebral ischemia/reperfusion injury / 中华行为医学与脑科学杂志

ABSTRACT

Objective To investigate the neuralprotective effect of Rho kinase inhibitor fasudil hydrochloride in cerebral ischemia/reperfusion injury in rats.Methods The SD rats were randomly divided into four groupsthe sham group,the ischemia/reperfusion group,the fasudil hydrochloride group and the physiological saline group.Fasudil hydrochloride were injected intraperitoneally 30 minutes before ischemia.And the physiological saline group were treated with the intraperitoneal injection of the same volume of saline.The phosphorylation and protein expression of GluR6 at 6 hours during reperfusion were detected using immunoprecipitation and immunoblotting analysis to examine the effect of Fasudil hydrochloride.Furthermore,TUNEL staining was used to examine the apoptosis of neurons in rat hippocampal CA1 regions after 3 days reperfusion.Results 1.Immunoprecipitation and immunoblotting analysis were used to analyze the phosphorylation of GluR6 in serine site.The results showed that the GluR6 serine phosphorylation level increased significantly at 6h of reperfusion compared with the sham group (P＜0.05).Fasudil hydrochloride group could inhibit the increased phosphorylation of GluR6 at 6h of reperfusion compared with the ischemia/reperfusion group and saline group,respectively (P ＜ 0.05).2.TUNEL staining was used to examine the apoptosis of neurons in 3 days after reperfusion in CA1 regions of hippocampus.The results indicated that significant numbers of TUNEL positive cells (40.20 ± 2.77) were observed 3 days after ischemia/reperfusion.The numbers of viable neurons per 1 mm length of CA1 pyramidal cells were quantitatively analyzed.Fasudil hydrochloride markedly decreased the neuronal loss compared with the ischemia/reperfusion group (19.80 ± 2.86) (P＜0.05).Conclusion Fasudil hydrochloride can inhibit induced phosphorylation of GluR6 by the ischemia/reperfusion.Fasudil hydrochloride can reduce the neurons apoptosis in hippocampal CA1 regions,and perform a neuralprotective effect on ischemia/reperfusion injury in rats.