白藜芦醇对热缺血/再灌注后大鼠肝脏中HIF-1α和VEGF表达的抑制作用

The suppressive effects of resveratrol on HIF-1α and VEGF expression after warm ischemia and reperfusion in rats liver

目的:探讨白藜芦醇对热缺血/再灌注后大鼠肝脏中HIF-1α和VEGF表达的抑制作用。方法:选取24只大鼠随机分为对照组,模型组和白藜芦醇处理组各8只,通过肝门动脉阻断1h后再灌注1h来建立缺血再灌注模型,白藜芦醇处理组在缺血再灌注前进行白藜芦醇20mg/kg预处理30min。建模后检测血清中ALT、ALP和TBIL的含量变化;肝脏中HIF-1α和VEGF表达通过RT-PCR和Western blot来检测。结果:与对照组相比,模型组大鼠血清中ALT、ALP和TBIL的含量及肝脏中HIF-1α和VEGF的mRNA和蛋白表达量均显著上升(P<0.05);与模型组相比,白藜芦醇20mg/kg预处理后大鼠血清中ALT、ALP和TBIL的含量及肝脏中HIF-1α和VEGF的mRNA和蛋白表达量均显著下调(P<0.05)。结论:白藜芦醇对热缺血/再灌注后大鼠肝脏中HIF-1α和VEGF表达具有抑制作用;因此,HIF-1α/VEGF可能是白藜芦醇在肝脏肿瘤中起抗癌作用的一个药物靶点。

Objective：The aim of the present study was to investigate the effects of resveratrol（RES）on the expression of ischemic-induced HIF-1αand vascular endothelial growth factor（VEGF）in rats liver.Methods：Twenty-four rats were randomized into Sham,ischemia/reperfusion（I/R）,and RES preconditioning groups.I/R was induced by portal pedicle clamping for 60 minutes followed by reperfusion for 60 minutes.The rats in RES group underwent the same surgical procedure as I/R group,and received 20mg/kg resveratrol intravenously 30 min prior to ischemia.Blood and liver tissue samples were collected and subjected to biochemical assays,RT-PCR,and Western blot assays.Results：I/R resulted in a significant（P0.05）increase in serum biochemical parameters and liver HIF-1αand VEGF at both mRNA and protein levels 60 minutes after reperfusion.The serum biochemical parameters and the mRNA and protein expressions of HIF-1αand VEGF decreased significantly in RES group when compared to I/R group（P0.05）.Conclusion：The inhibiting effects of RES on the expressions of HIF-1αand VEGF induced by I/R in rats liver suggested that HIF-1α/VEGF can be a promising drug target for RES in the development of an effective anticancer therapy for the prevention of hepatic tumor growth and metastasis.