Effect Of Fasudil On The Expression Of P-JAK2 And P-STAT3 Protein After Focal Cerebral Ischemia/reperfusion In Rats

Objective To study the effect of Fasudil on nerronal deficits, neuronal apoptosis,and the expression of P-JAK2 and P-STAT3 after Focal Cerebral Ischemia/reperfusion in Rats.Methods The middle cerebral artery occlusion(MCAO) models were established by using the intraluminal suture occlusion method in Sprague-Dawley rats.Adult male Sprague-Dawley rats weighing 250-300g were randomly divided into normal group,sham-operated group,ischemia/reperfusion model group,Fasudil treatment group (intraperitoneal injected Fasudil 15mg/kg immediately after ischemia/reperfusion) and saline treatment group(intraperitoneal injected the same dose physiological saline immediately after ischemia/reperfusion).Normal control group included six rats;Other rats were randomly divided into six sub-groups as follows:3h,6h,12h, 24h,48h and 72h treatment groups,according to the killing time after ischemia/reperfusion,each sub-group included five animals.The changement of neuronal deficits accepted dynamic observation. Pathologic changes were evaluated by Hematoxylin.The expressions of P-JAK2 and P-STAT3 were detected by immunohistochemistry,and the neuronal apoptosis in ischemia/reperfusion rat brains were evaluated by TUNEL assay.Result1.The effect of Fasudil on the changement of neuroethology after ischemia/reperfusion:The normal control group and sham-operated group had no significant nerronal deficits.The ischemia/reperfusion model group and saline treatment group respectively showed more severe nerronal deficits than Fasudil treatment group(P＜0.05 for each), indicating Fasudil may improve the symptoms of neurological deficits.2.The effect of Fasudil on the expressions of P-JAK2 and P-STAT3 after ischemia/reperfusion:The expressions of P-JAK2,P-STAT3 in the normal control group and sham-operated group were rare observed.The expressions of P-JAK2 and P-STAT3 in ischemic part of model groups reached the peak at the time point of 24 hours after reperfusion(P＜0.05),Fasudil significntly decreased the expressions of P-JAK2 and P-STAT3 at the same time point(P＜0.05),indicating Fasudil could inhibit the expressions of P-JAK2,P-STAT3.3.The effect of Fasudil on neuronal apoptosis after ischemia/ reperfusion:The apoptotic cells in the sham-operated group were rare observed.The amount of apoptotic cells in ischemic part of model groups reached the peak at the time point of 24 hours after reperfusion (P＜0.05),Fasudil significntly decreased the amount of apoptotic cells at the same time point(P＜0.05),indicating Fasudil could inhibit the amount of apoptotic cells.Conclusion1.The expressions of P-JAK2 and P-STAT3 can be up-regulated by the focal cerebral ischemia/reperfusion in rats.2.The increased expression of P-JAK2 and P-STAT3 may participate in the pathophysiological process of nerronal deficits induced by ischemia/reperfusion.3.Fasudil could be a potent neutoprotector by inhibiting the signal pathway involving the JAK2/STAT3 to reduce the amount of apoptotic cells and nerronal deficits.