DL0805抑制血管紧张素Ⅱ通过Ca^(2+)依赖和非Ca^(2+)依赖途径引起的大鼠胸主动脉环收缩  

DL0805 inhibits the vasoconstriction induced by angiotensin Ⅱ in a Ca^(2+)-dependent and Ca^(2+)-independent manner in the rat aorta

作　　者：李莉[1] 袁天翊[1] 郭晶[1] 方莲花[1] 杨海光[1] 张莉[1] 杜冠华[1] 

机构地区：[1]中国医学科学院&北京协和医学院药物研究所,药物靶点研究和新药筛选北京市重点实验室,北京100050

出　　处：《首都医科大学学报》2013年第3期398-403,共6页Journal of Capital Medical University

基　　金："重大新药创制"国家科技重大专项资助项目(2009ZX09302-003;2013ZX09103001-008);国家自然科学基金(81102444;81102492)~~

摘　　要：目的探讨Rho激酶抑制剂DL0805抑制血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)收缩大鼠胸主动脉环的机制。方法体外培养大鼠胸主动脉平滑肌细胞(vascular smooth muscle cell,VSMC),在有/无1.8 mmol/L Ca2+的环境下采用Fura2/AM荧光探针法测定细胞内游离钙(intracellular calcium,[Ca2+]i)的变化。应用Western blotting检测大鼠胸主动脉环肌球蛋白磷酸酶靶亚基1(myosin phosphatase target subunit 1,MYPT1)和Akt蛋白磷酸化,以及Rho激酶1(Rho kinase 1,ROCK1)蛋白表达水平。结果 DL0805(1、10μmol/L)抑制AngⅡ(100 nmol/L)引起的VSMC细胞内钙释放和外钙内流。DL0805(25、50μmol/L)抑制AngⅡ(100 nmol/L)引起的MYPT1和Akt磷酸化水平以及ROCK1蛋白表达水平增高。结论 DL0805能抑制AngⅡ通过Ca2+依赖和非Ca2+依赖途径引起的大鼠胸主动脉环收缩。Objective To investigate the mechanisms of DL0805, a Rho kinase inhibitor, in the relaxation on the contraction induced by angiotensin Ⅱ （ Ang Ⅱ ） in the rat thoracic aorta. Methods Intracellular [ Ca^2＋ ] （ [ Ca^2＋ ] i） was measured with Fura2/AM in vascular smooth muscle cell（VSMC）. Protein level of Rho kinase 1 （ ROCK1 ） , the phosphorylation levels of myosin phosphatase target subunit 1 （ MYPT1 ） and Akt in the rat aortic rings were detected by Western blotting. Results DID805 （ 1, 10 μmoL/L） were shown to inhibit both Ang Ⅱ （100 nmol/L）-induced Ca^2＋ release from internal stores and Ca^2＋ influx. DL0805 （25,50 μmol/L） significantly attenuated the increased protein level of ROCK1, the increased phospholylation levels of MYPT1 and Akt in the aorta stimulated by Ang Ⅱ （100 nmol/L）. Conclusions DL0805 inhibits the vasoconstriction induced by Ang Ⅱ in a Ca^2＋ -dependent and Ca^2＋ -independent manner in the rat thoracic aorta.

关 键 词：DL0805 血管紧张素Ⅱ 大鼠胸主动脉环 细胞内游离钙 RHO激酶 血管平滑肌细胞 

分 类 号：R966[医药卫生—药理学]