大鼠脑缺血再灌注损伤时脑组织血管内皮生长因子和内皮抑素的变化

目的 探讨大鼠脑缺血再灌注损伤时脑组织血管内皮生长因子(VEGF)和内皮抑素(ES)的变化.方法 雄性Wistac大鼠48只,体重270～330 g,随机分为2组:假手术组(S组,n=8)和脑缺血再灌注组(IR组,n=40).IR组采用改良的Zea Longa线栓法阻断大鼠左侧大脑中动脉建立局灶性脑缺血再灌注模型,缺血90 min时拔出线栓行再灌注.S组只插入线栓,不阻断大脑中动脉.S组于术后1 d时、IR组分别于再灌注6 h、1、2、4、7 d时,取8只大鼠进行神经功能损伤评分,然后处死,取脑组织,观察脑梗死情况,采用RT-PCR法测定VEGF mRNA和ES mRNA的表达,计算其比值(ES/VEGF).结果 与S组相比,IR组再灌注各时点神经功能损伤评分升高,脑组织VEGF mRNA表达上调,再灌注1、2、4、7 d时脑组织ES mRNA表达上调,再灌注2、4、7 d时脑组织ES/VEGF降低(P<0.01).再灌注2 d时神经功能损伤评分最高,VEGF mRNA表达及ES/VEGF至谷值,ES mRNA表达至峰值,脑梗死最严重.结论 大鼠脑缺血再灌注时VEGF mRNA和ES mRNA表达上调,且脑损伤程度与脑组织ES和VEGF的平衡状态有关.

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

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 At 90 min of MCAO, the nylon thread was withdrawn to allow reperfusion.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.