肾脏花生四烯酸CYP p450羟化酶参与高血压的形成及维持正常血压的稳定  

Cytochrome p450 Arachidonic Acid Hydroxylases of Kidney Substantially Contribute to the Formation of High Blood Pressure and Maintenance of Blood Pressure

作　　者：张帆[1] 钱家庆[2] 汪道文[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院内科,武汉430030 [2]华中科技大学同济医学院药理学教研室,武汉430030

出　　处：《中国分子心脏病学杂志》2002年第3期11-16,共6页Molecular Cardiology of China

基　　金：国家自然科学资助课题(No39870307)

摘　　要：目的:研究肾脏特异性表达CYP4A1与血压变化的关系。方法:将含有开放阅读框的CYP 4A1cDNA克隆到真核表达载体pcDNA3.1,构建4A1/pcDNA3.1和反义4A1/pcDNA3.1重组体,舌下静脉注射转染SD雄性大鼠(2mg/kg),经尾动脉测量收缩压。用Western blots及Northern blots分析转染对照pcDNA3.1质粒,及正、反义CYP 4A1重组体后,CYP 4A1在大鼠的脑,心,肺,肝,肾组织表达水平。结果:两周后,转染正义、反义CYP 4A1的大鼠,血压与对照组相比分别增加1.73±0.33 kPa(13±2.5mmHg)和减少了1.73±0.29 kPa(13±2.2mmHg)。Western blots及Northern blots结果均显示CYP4A1可选择性地在。肾脏表达,而在脑、心、肺、肝几无表达,且在给予反义CYP 4A1的大鼠,其肾脏中CYP 4A1蛋白表达几乎被完全阻断。结论:在正常的SD大鼠肾脏中,转染正、反义p450 CYP4A1可引起血压升高和降低,说明肾脏花生四烯酸CYP p450羟化酶参与高血压的形成及维持正常血压的稳定。Aim： To investigate the relationship of kidney-specific expression of cytochrome P-450 （CYP）4A1 and the blood pressure. Methods： The specific sense and antisense CYP4A1 cDNA were administered respectively with the help of eukaryotic expression vector pcDNA3.1 to the Sprague- Dawley （SD）rats via sublingual vein （2mg/kg）. The systolic blood pressure of rats was assessed by the tail- cuff method, and the relative tissue expression of CYP4A1 was analyzed at RNA and protein levels from the brains, hearts, pulmonaries, livers, kidneys of control, sense-and antisenseCYP4A1 cDNA treated rats. Results： The mean systolic pressure of.the transgenic rat increased 1.73 ± 0.33kPa （ 13 ± 2.5mmHg）or decreased 1.73 ± 0.29kPa （13 ± 2.2mmHg）two weeks after the injection of the sense and antisense CYP4A1 eDNA recombinants respectively, compared with controls. At the levels of transcription and translation, the Northern and Western blots all demonstrated that CYP4A1 preferentially overexpressed in the kidney. Conclusion： The administrations of sense-and antisense CYP4A1 eDNA induced hypertension and hypotension, respectively, relating to the kidney-specific expression of CYP4AlcDNA, in normotensive rats.

关 键 词：花生四烯酸 单氧化酶 羟化酶 细胞色素 P-450 4A1 高血压 20-羟花生四烯酸 肾脏 

分 类 号：R544.1[医药卫生—心血管疾病]