Effects Of Insulin On Expression Of VEGF Protein In Rats Following Cerebral Ischemia- Reperfusion

Background and Objective Vascular endothelial growth factor (VEGF) is a potent angiogenic factor stimulating the proliferation and migration of endothelial cells, and is also known as a vascularpermeability factor. Some reports have demonstrated that VEGF improvesrecovery of sensorimotor and cognitive deficits after focal cerebral ischemia in the rat. Recent years some studies indicated insulin has neuroprotective role and can reduce cerebral ischemia reperfusion injury, and insulin in blood is thought to cross the blood-brain barrier (BBB) to act within the brain, but the exact mechanism of neuroprotective of insulin remains unclear. Yamagishi et al have demonstrated that insulin stimulates the growth and tube formation of human microvascular endothelial cells through autocrine VEGF in vitro. Nevertheless the effect of insulin on the expression of VFGF protein in rat with cerebral ischemia-reperfusion is still unknown. So in this study, we investigated the effect of insulin on the expression of VEGF protein in rat with cerebral ischemia-reperfusion and to explore the mechanism of the effect.Methods Forty-four adult rats used in the experiment were divided into sham operation, control and insulin groups. The cerebral ischemia model of the rats were made with intraluminal suture to occlude the middle cerebral artery of the rats. The insulin was administered in insulin group rats by intraperitoneal injection and glucose was given before operation to maintain systemic glucose in normal range. Expression of VEGF was examined with immunohistochemistry method.Results In the ischemic penumbra area of brain in insulin group and control groups rats, the positive expression of VEGF in some nerve cells occurred at 6th hour after reperfusion, increased significantly at 12th hour and reached peak at 24th hour. Thereafter the expression of VEGF weakened gradually and at 3rd day there was a little positive nerve cells. The expression level of VEGF in the insulin group was significantly higher than that in the control group at 12 hours and 24 hours after reperfusion (P<0.05). The expression of VEGF was not found in the ischemic central or non-ischemic area.Conclusions Insulin enhance VEGF expression after cerebral ischemia reperfusion, which may be one of the mechanism of neuroprotection of insulin.