肾性高血压大鼠内皮脂肪酶表达与血管重构的关系及机制初探

论著

肾性高血压大鼠内皮脂肪酶表达与血管重构的关系及机制初探

陈永宏1，周建中2，张松涛1

（1．重庆市长寿区人民医院心内科，重庆401220；2．重庆医科大学附属第一医院心内科，重庆400016）

【摘要】目的检测两肾一夹(2K1C)高血压大鼠大动脉内皮脂肪酶(EL)、核转录因子-κB(NF-κB)及血管重构的

动态变化，探讨EL与血管重构的关系及可能机制。方法制作2K1C高血压模型，随机分成假手术组(Sham，n=7)、

2K1C4W组(n=7)、2K1C8W组(n=7)、2K1C12W组(n=7)四组，观察四组大鼠血压、血脂、主动脉中层壁厚/管腔内径(MT/LD)变化，用免疫组化观察EL、NF-κB表达，用实时荧光定量RT-PCR检测EL mRNA表达。结果2K1C8W与12W

组高密度脂蛋白(HDL)水平显著低于Sham组;主动脉MT/LD2K1C各组显著高于Sham组，且随时间延长MT/LD进行

性增大;EL、EL-mRNA、NF-κB表达2K1C各组显著高于Sham组，且随时间延长进行性升高;EL、NF-κB表达与MT/LD正

相关，EL与HDL负相关。结论高血压大动脉中EL表达明显增高，且与其血管重构关系密切，可能是血管重构机制之一。

【关键词】内皮脂肪酶;血管重构;高血压

【中图分类号】R-332【文献标识码】A【文章编号】1004-0501(2012)12-2065-03

The research of the relationship between the expression of endothelial lipase and vascular remodeling and its mecha-nism in renal hypertensive rats．CHEN Yong-hong1，ZHOU Jian-zhong2，ZHANG Song-tao1．1．The People’s Hospital of Chan-gshou，Chongqing401220；2．The First Affiliated Hospital，Chongqing Medical University，Chongqing400016，China 【Abstract】Objective To explore the relation between endothelial lipase（EL）and vascular remodeling of the main arter-

y and its possible mechanism by detection the dynamic changes of EL，nuclear transcription factor-κB（NF-κB）and vascular re-modeling of the main artery in two-kidney one-clip（2K1C）hypertensive rats．Methods Productive model of2K1C hyperten-sion，were randomly divided into sham operation group（Sham，n=7），2K1C4W group（n=7），2K1C8W group（n=7），2K1C

12W group（n=7）．Blood pressure were detected with the method of tail cuff，lipids with fully automatic biochemical analyzer，the ratio of aortic intima media thickness to lumen diameter（MT/LD）with HE staining，the expression of EL and NF-κB with immu-nohistochemical staining，and the expression of EL-mRNA with Real-time quantitative RT-PCR．Results High-density lipopro-

tein（HDL）levels of2K1C8W and2K1C12W groups was significantly lower than Sham group；Both MT/LD and the expression of EL，EL-mRNA，and NF-κB of2K1C groups was significantly higher than the Sham group，and was gradually increased with time extended；the expression of EL，NF-κB were positively related with MT/LD，negatively with HDL．Conclusion The significantly increased EL expression of the main artery are closely related with vascular remodeling，and may be one of the mechanisms of vas-cular remodeling．

【Key words】endothelial lipase；vascular remodeling；hypertension

内皮脂肪酶（endothelial lipase，EL）是近年发现的脂肪酶家族新成员，由内皮细胞合成分泌并于细胞表面发挥作用，EL可能参与了血管壁重构与动脉粥样硬化［1］。高血压是动脉粥样硬化性疾病的危险因素，其致血管重构及动脉粥样硬化的机制目前仍不完全清楚。本研究构建两肾一夹（2K1C）高血压大鼠模型，研究EL、核转录因子-κB（NF-κB）与大动脉重构的动态变化及其相关性，初步探讨EL与高血压血管重构的关系。

1材料与方法

1.1动物模型制备与分组：健康SD雄性大鼠30只，体重（200ʃ20）g，购自重庆医科大学实验动物中心。随机分成四组：假手术组（Sham，n=7）、其余2K1C三组（2K1C，n=23）。2K1C高血压大鼠模型按经典2K1C模型方法制备。术后4周测尾动脉收缩压（SBP）≥150mmHg者为高血压模型制备成功。将造模成功大鼠21只，随机分成三组：2K1C高血压4周组（2K1C4W，n=7）、2K1C高血压8周组（2K1C8W，n= 7）、2K1C高血压12周组（2K1C12W，n=7）。2K1C 4W组和2K1C8W组分别在术后4W和8W处死，2K1C12W组和Sham组于术后12W处死。在实验过程开始、4周、8周、12周用鼠尾测压仪测定血压。