intermedin对肾脏缺血再灌注损伤后血管再生相关因子表达的影响  

Effect of intermedin on the expressions of angiogenesis-related genes induced by renalischemia reperfusion injury

作　　者：赵海红[1] 李荣山[1] 乔晞[1] 赵莉[1] 刘新艳[1] 邵珊[1] 

机构地区：[1]山西医科大学第二医院肾内科山西省肾脏病研究所,太原030001

出　　处：《中华肾脏病杂志》2011年第12期912-916,共5页Chinese Journal of Nephrology

基　　金：国家自然科学基金项目（30971380）;山西省科技攻关项目（20080311061-6）

摘　　要：目的观察intermedin（IMD）对肾脏缺血再灌注损伤（IRI）后血管生长相关因子缺血诱导因子1仪（HIF．1d）、血管内皮生长因子（VEGF）和血管生成素受体Tie-2表达的影响。探讨intermedin对肾脏IRI的修复作用。方法Wistar大鼠按随机数字表法分为4组：假手术组、IRI组、转空质粒组、转IMD质粒组。大鼠右肾切除后1周，用超声微泡造影剂介导的基因转染方法将大鼠IMD真核表达质粒转染大鼠肾脏，转染成功后夹闭左肾动脉45min制作肾脏IRI模型。分别于再灌注1d、2d、3d、4d、7d和14d后留取肾组织标本，采用RT-PCR检测HIF-1α、VEGF和Tie-2的mRNA表达；Western印迹法检测肾组织VEGF的蛋白表达；ELISA检测HIF-1α和Tie-2的蛋白表达。结果与假手术组相比，IRI组HIF-1α mRNA和蛋白质表达于再灌注后1d达到高峰，2d时持续高表达，3d时表达开始明显下降，4d、7d和14d时接近于假手术组；VEGF和Tie-2表达均于再灌注后1d开始增加，2d达到高峰，3d开始下降，4d、7d和14d接近于假手术组；转IMD质粒组大鼠肾组织HIF-lα、VEGF和Tie-2mRNA和蛋白质的表达于再灌注后1d、2d、3d和4d显著高于同时问点的IRI组大鼠（均P〈0．05），并且均于再灌注后1d表达达到高峰，2-3d持续表达，4d开始下降，7d和14d的表达无明显改变。上述各指标在转空质粒和IRI组之间的表达差异无统计学意义。结论肾脏局部高表达的IMD不仅促进了肾脏IRI后血管再生相关因子HIF-1α、VEGF和Tie-2的表达，而且使表达高峰提前并延长了表达时间，可能参与了肾脏组织的修复和再生。Objective To investigate the effect of intermedin （IMD） on the expressions of angiogenesis related genes induced by renal ischemia reperfusion injury （IRI）. Methods Wistar rats were randomly divided into four groups： control group, IRI group, empty plasmid group and IMD plasmid group. One week after removing the right kidney, eukaryotic expression vector encoding rat IMD gene was transfected into the left kidney using an ultrasound-microbubble mediated system. Renal IRI model was induced by clamping left renal arteries for 45 minutes followed by reperfusion for 1 d, 2 d, 3 d, 4 d, 7 d and 14 d. The expressions of hypoxia inducible factor-lα （HIF-lα）, vascular endothelial growth factor （VEGF） and angiopoietin receptor Tie-2 were examined by RT-PCR and Western bohting. Results Compared with control group,an increase in HIF-lα, VEGF and Tie-2 was observed in the IRI group at d 1, d 2 and d 3 （all P〈0.05）. The expression of HIF-lα peaked at d 1 d（P〈0.05）, while VEGF and Tie-2 at d 2 （P〈 0.05）, followed by a decrease that was similar to the control levels at d 4 （P〉0.05）. Compared with the IRI group, the expressions of HIF-α,VEGF and Tie-2 of IMD group were much higher and all reached the peak at d 1 （P〈0.05）, maintained at d 2-4 （P〈0.05）, followed by a decrease at d 7 （P〉0.05）. The above indexes had no differences between empty plasmid group and IRI group （P〉0.05）. Conclusions IMD pretreatment may play an important role in the process of repair and regeneration after renal ischemia reperfusion injury by improving the expressions of angiogenesis related genes（HIF-lα,VEGF and Tie-2） induced by renal ischemia reperfusion injury.

关 键 词：再灌注损伤 肾功能不全 急性 血管内皮生长因子类 INTERMEDIN 

分 类 号：R285.5[医药卫生—中药学]