Changes in vascular endothelial growth factor and endostatin in rat brain tissues following cerebral ischemia-reperfusion injury

Abstract

Objective To investigate the changes in vascular endothelial growth factor (VECF) and endostatin (ES) in rat brain tissues following cerebral ischemia-reperfusion (IR) injury. Methods Forty-eight male Wistar rats weighing 270-330 g were randomly divided into 2 groups: sham operation group (group S, n = 8) and IR group ( n = 40). The animals were anesthetized with intraperitoneal chloral hydrate 3 ml/kg. Left common, internal and external carotid arteries (CCA, ICA, ECA) were exposed. Middle cerebral artery occlusion (MCAO) was produced by inserting a nylon thread 17-19 mm in length into ICA and advancing it cranially until resistance was felt using Zea Longa's method. At 90 min of MCAO, the nylon thread was withdrawn to allow reperfusion. In group S, the nylon thread was inserted 10 mm in length into ICA but no MCAO was performed. The neurological deficit was scored at 1 d after operation in group S, and at 6h, 1 d, 2 d, 4 d and 7 d of reperfusion in group IR (8 animals at each time point) . The rats were then killed and the brains were removed and sliced. Brain tissue slices from 2 out of the 8 rats were stained with triphenyl tetrazolium chloride to estimate the infarct size, while those from the other 6 rats were used to determine the expression of VEGF mRNA and ES mRNA using RT-PCR. ES/VEGF ratio was calculated. Results Compared with group S, neurological deficit score was significantly increased and VEGF mRNA expression in brain tissues was up-regulated at each time point following reperfusion, ES mRNA expression in brain tissues was up-regulated at 1, 2, 4 and 7 d of reperfusion, and ES/VEGF ratio in brain tissues was significantly decreased at 2, 4 and 7 d of reperfusion in group IR ( P < 0.01). The neurological deficit score was the highest, expression of VEGF mRNA and ES/VEGF ratio reached the valley value ES mRNA, expression reached the peak value, and infarct size was the largest at 2 d of reperfusion. Conclusion The expression of VEGF mRNA and ES mRNA is up-regulated during cerebral IR in rats and the degree of brain injury may be related to the balance of ES and VEGF in brain tissues. Key words: Reperfusion injury; Brain; Endostatins; Vascular endothelial growth factors