ERK1/2及JNK参与DL0805抑制血管紧张素Ⅱ引起的大鼠离体胸主动脉环收缩  

ERK1/2 and JNK are involved in the inhibitory effect of DL0805 on vasoconstriction induced by angiotensin Ⅱ in the rat thoracic aortic rings

作　　者：李莉[1] 袁天翊[1] 杨海光[1] 许焕丽[1] 王乐[1] 阎雨[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：《基础医学与临床》2013年第6期699-703,共5页Basic and Clinical Medicine

基　　金：国家自然科学基金青年基金(81102444);中央级公益科研院所基本科研业务费(2011CHX14;2013ZD02)

摘　　要：目的研究Rho激酶抑制剂DL0805对血管紧张素Ⅱ(AngⅡ)引起的大鼠离体胸主动脉环收缩反应的影响及其可能的机制。方法测定离体血管张力观察大鼠胸主动脉环收缩反应,Western blot检测大鼠离体胸主动脉环ERK1/2和JNK蛋白磷酸化,和AngⅡ1型受体(AT1R)蛋白表达水平。结果 DL0805(10、25和50μmol/L)浓度依赖性地抑制AngⅡ(100 nmol/L)引起的内皮完整或去内皮的大鼠离体胸主动脉环收缩(P<0.01,P<0.001),DL0805(25和50μmol/L)抑制AngⅡ(100 nmol/L)诱导的ERK1/2和JNK的活化(P<0.05,P<0.01和P<0.001),但DL0805(5、25和50μmol/L)对AngⅡ刺激的血管环AT1R蛋白表达水平无显著影响。结论 DL0805抑制AngⅡ引起的大鼠离体胸主动脉环收缩,其机制可能与其抑制AngⅡ诱导的ERK1/2和JNK活化有关。Objective To observe the effect of DL0805 （a Rho kinase inhibitor） on angiotensin lI （Ang H ）-in- duced vascular contractions in the rat thoracic aortic tings and to investigate the possible mechanism. Methods The isometric vascular tone was measured in both endothelium-intact and endothelium-denuded rat thoracic aortic tings. Phosphorylations of p44/42 extracellular signal-regulated kinase （ERK1/2） and c-Jun amino-terminal ki nase （JNK）, and protein level of angiotensin type 1 receptor （ATIR） in rat aortic tings were detected by Western blot. Results DL0805 （ 10, 25 and 50 txmol/L） inhibited Ang I1 （ 100 nmol/L）-induced vascular contractions in both endothelium-intact and endothelium-denuded rat aortic rings in a dose dependent way （P 〈 0. 01, P 〈 0. 001 ）. Furthermore, activation of ERK1/2 and JNK by Ang ]I （ 100 nmol/L） stimulation was significantly inhibi ted by DL0805 （25 and 50 izmol/L） in both endothelium-intact and -denuded rat aortic rings （P 〈0. 05, P 〈0.01 and P 〈0. 001）. However, the protein level of ATIR in response to Ang II was not affected by DL0805 （5, 25 and 50 txmol/L） in rat aortic tings. Conclusions DL0805 inhibits Ang 11-induced rat aortic tings contraction and the mechanism involves the inhibition of Ang Ⅱ -induced ERK1/2 and JNK activation.

关 键 词：DL0805 血管紧张素Ⅱ 大鼠胸主动脉环 ERK1/2 JNK 

分 类 号：R966[医药卫生—药理学]