人促肾上腺髓质素基因导入对高盐饮食诱导的高血压大鼠血压及心肾功能的影响  

Delivery of human adrenomedullin gene mediates reductions in blood pressure and the protects heart and kidney function in high-salt diet induced hypertensive rats

作　　者：魏欣[1] 赵春霞[1] 蒋建刚[1] 刘珍君[1] 肖啸 LEE Chao 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心内科,武汉430030 [2]美国匹茨堡医学院分子遗传和生物化学中心 [3]美国南卡罗莱那医学院生物化学系

出　　处：《临床心血管病杂志》2004年第6期349-352,共4页Journal of Clinical Cardiology

基　　金：国家高技术发展计划 (86 3计划 )资助 (No :2 0 0 1AA2 1712 1)

摘　　要：目的 :研究人促肾上腺髓质素 (AM)基因导入对高盐饮食诱导的高血压大鼠的降压作用和对心、肾功能的保护作用。方法 :8周龄雄性Wistar大鼠以高盐 (8%氯化钠 )饲料及 0 .85 %氯化钠喂养 8周后形成高血压动物模型。再经尾静脉注射含人AMcDNA的重组质粒。然后监测血压 ;收集尿液以测定尿微量清蛋白 ;处死动物前插管测定心功能 ,处死动物后测定人AM基因在各主要器官的表达。结果 :一次静脉注射人AM基因的重组质粒后的第 4天即出现降低高盐饮食诱导的高血压大鼠的血压 ,最大降压效应出现在导入AM基因后的第 12天 ;实验组动物血压降低的同时 ,尿微量清蛋白的值亦出现显著下降 ;实验组右侧颈总动脉插管测定的心功能较对照组显著改善。结论 :人AM基因的导入可能有助于降低血压 ,并预防高血压所导致的心、肾功能损害。为临床应用AM基因治疗并发心、肾功能损害的原发性高血压提供了可能。Objective: To investigate the effects of AM gene on high-salt diet rats' blood pressure, heart and renal function. Method: Eighteen male Wistar rats were allocated randomly into three groups: normal diet, high-salt diet with rAAV-D(+) and high-salt diet with rAAV-D(+)-AM group. A high-salt diet (8% NaCl) or normal diet was given for 8 weeks. Blood pressure and urine Alb were observed during the experiment. At the end, we measured rats' heart function. The expression of AM were detected by RT-PCR. Result: High-salt-fed rats developed slightly but significantly higher systolic blood pressure than controls (P< 0.01). After delivery of human AM in high-salt diet rats, a maximal blood pressure difference of 15 mmHg was observed (P< 0.01). Human adrenomedullin delivery significantly attenuated increase in the amount of urine A1b of rats (P< 0.01). And cardiaovascular dynamic assessments were improved at the end of the experiment (P< 0.05). The expression of human adrenomedullin was detected in rat main organs. Conclusion: Human adrenomedullin gene can decrease blood pressure and protect heart and renal function in high-salt diet induced hypertensive rats.

关 键 词：高血压 促肾上腺髓质素 基因 

分 类 号：R544.1[医药卫生—心血管疾病] R459.9[医药卫生—内科学]