Effect Of Fasudil On Expression Of VEGF, Ang-1 And Factor Ⅷ After Focal Cerebral Ischemia/reperfusion In Rats

Objective We study the expression of protein of VEGF,Ang-1 and factorâ…§as well as the effect of Fasudil on the expression of them after focal cerebral ischemia/reperfusion in rats,so as to explore the contribution of VEGF, Ang-1 and factorâ…§to cerebral ischemia and the remedial mechanism of Fasudil in the treatment of ischemic cerebrovascular disease .We expect that our study could provide experimental foundation for us to further study the pathomechanism of angiogenesis secondary to cerebral ischemia and the prevention and treatment of cerebral infarction.Methods The middle cerebral artery occlusion(MCAO) models were established by using the intraluminal suture occlusion method in SD rats. One hundred and twenty-six male SD rats were divided randomly into: normal control group (NG), sham operated group (SG), model group(MG), physiologic saline group(PG) and Fasudil group(FG). There are six rats in the normal control group , other groups were each divided randomly into ischemia for two hours and reperfusion for three hours, six hours, twelve hours, twenty-four hours, foyty-eight hours and seventy-two hours, in total six time point in every group and each time point has five rats. In Fasudil group, Fasudil was given immediately after reperfusion by 15 mg/kg abdominally. In physiologic saline group, the same dose physiologic saline was given abdominally immediately after reperfusion. Pathologic changes were evaluated by Hematoxylin and eosin stain. The expressions of VEGF, Ang-1 and factorâ…§were detected by immunohistochemistry.Result1. There was no neurologic impairment in the rats of the normal control group and the sham operated group,while the neurologic impairment appeared in the model groups , physiologic saline groups and Fasudil groups. But compared with the model groups and the physiologic saline groups ,the neurologic impairment of Fasudil groups could improve quickly, the neurobiology score had significant difference.(P<0.05). 2. There was almost no expressions of VEGF in the brain tissue of rats which was detected by immunohistochemistry in the normal control groups,while a little was detected in the sham operated groups and the expressions of VEGF were detected in every time point in the model groups and physiologic saline groups,reaching peak in the 24th hour,compared with the normal control groups and the sham operated groups had significant difference.(P<0.05).3.The expressions of Ang-1 were detected in every group by immunohistochemistry, of which there was only a little weakly positive detected in the normal control groups and the sham operated groups, while in the model groups and physiologic saline groups, the expressions of Ang-1 were detected in every time point and began to increase in the 3rd hour , but also the upregulating tendency extented to the 72th hour after, compared with the normal control groups and the sham operated groups had significant difference.(P<0.05).4.The expressions of factorâ…§were detected in the brain tissue of rats in every group by immunohistochemistry, of which there was strongly positive detected in the normal control groups and the sham operated groups. The positive expressions mainly appeared in the vascular endothelial cells. The expressions of factorâ…§decreased in the 3rd hour in the model groups and physiologic saline groups, reaching bottom in the 24th hour , compared with the normal control groups and the sham operated groups had significant difference. (P<0.05).5.The Fasudil groups were detected by immunohistochemistry, the varietying tendency of the expressions of protein of VEGF, Ang-1 and factorâ…§in the brain tissue of rats was the same as the model groups and physiologic saline groups, but the positive expression is higher than the model groups and physiologic saline groups, compared to the same time point ,there was significant difference.Conclusion1. The expressions of protein of VEGF, Ang-1 and factorâ…§in the penumbral region after cerebral ischemia/reperfusion in rats indicates that angiogenesis is one of the mechanisms of the brain tissue repair in ischemic cerebrovascular disease. 2.Compared with the model groups and physiologic saline groups, the expressions of VEGF,Ang-1 and factorâ…§in the Fasudil groups were upregulated in each time point, with the brain tissue injury relieved, which indicates that Fasudil may could promote the expression of angiogenine after cerebral ischemia. This maybe a new therapeutic mechanism for Fasudil in the treatment of ischemic cerebrovascular disease.