肾上腺髓质素2的降压作用及其机制  

The antihypertensive effect of adrenomedullin 2 and related mechanism

作　　者：谢静[1,2] 崔屹[1] 耿彬[2] 唐朝枢[2] 曾强[1] 

机构地区：[1]中国人民解放军总医院国际医学中心,北京100853 [2]北京大学基础医学院生理学与病理生理学系,北京100191

出　　处：《中国应用生理学杂志》2014年第3期193-197,共5页Chinese Journal of Applied Physiology

基　　金：国家自然科学基金资助项目(81170235);国家科技支撑计划(2012BAI37B04)

摘　　要：目的：研究肾上腺髓质素2（ADM2）拮抗血管紧张素Ⅱ（AngⅡ）发挥舒张血管的作用及机制。方法：将18只180～200g雄性SD大鼠随机分为3组（n=6）：对照组、AngⅡ（150ng／（kg·min））组和AngⅡ（150ng/（kg·min））＋ADM2（500ng／（k·h））组，采用皮下埋植微量渗透泵的方法给药。2周后颈动脉插管法测量大鼠血压，测定血浆一氧化氮（NO）含量和内皮型一氧化氮合酶（eNOS）活性。DHE染色法检测大鼠动脉壁活性氧产生。制备大鼠离体血管环，观察ADM2的舒血管作用。培养人脐静脉内皮细胞系EA．hy926，用DCFH-DA荧光探针检测AngⅡ和ADM2对血管内皮细胞活性氧释放的影响。结果：与AngⅡ组相比，ADM2显著降低了大鼠血压，血浆中eNOS活性提高、NO含量增加，血管壁活性氧产生减少。ADM2呈浓度依赖性和内皮依赖性舒张血管环，并明显抑制了AngⅡ引起的血管内皮细胞活性氧产生。结论：ADM2可能通过拮抗AngⅡ诱导的血管内皮氧化应激效应，改善内皮功能，发挥舒张血管、降低血压的作用。Objective： To observe the vasedilating effect of adrenomedullin 2 （ADM2） by antagonizing angiotensin Ⅱ（Ang Ⅱ）, and to explore its mechanism. Methods： Eighteen male, 180 - 200 g SD rats were randomly divided into 3 groups （ n = 6） ： control group, Angll （150 ng/（kg-min） ） group and AngⅡ （150 ng/（kg·min） ） ＋ ADM2（500 ng/（kg·h） ） group. Mini-osmotic pumps filled with peptide were implanted in the back of rats subcutaneously. After two weeks, the blood pressure was measured by the way of carotid inttrbatian. The plasma was collected for the detection of nitric oxide （NO） content and the activity of endothelial nitric oxide synthase （eNOS）. The in situ oxidation of fluorescent dye dihydroethidium （DHE） was used for detecting superoxide in rat arteries. The rat isolated arterial rings were made for studying the vasodilating effect of ADM2. Human umbilical vein endothelial cell hne EA. hy 926 cells were ctdtured and their intracellular reactive oxygen species （ROS） were evaluated by probe DCFH-DA. Results： ADM2 dramatically decreased the blood pressure in angiotensin Ⅱ-in- duced hypertension rat model, enhanced plasma NO content and the activity of eNOS and reduced superoxide formation in vessel walls. ADM2 also induced relaxation of the vascular rings preconstricted by Ang Ⅱ in a concentration-dependent and endothelium-dependent manner. In cultured vascular endothelium, ADM2 ameliorated the ROS generation induced by AngⅡ .Conclusion： Adrenomedttllin 2 relaxed blood vessels by antagonizing angiotensin Ⅱ-induced oxidative stress and improving the vascular endothelial function. [KEY WORDS] hypertension; adrenomedullin 2; oxidative stress; endothelial dysfunction

关 键 词：高血压 肾上腺髓质素2 氧化应激 内皮功能障碍 

分 类 号：R331[医药卫生—人体生理学]