Urotensin Ⅱ对心功能的影响及其作用机制探讨  

Effect of Urotensin Ⅱ on Cardiac Function and Its Mechanism

作　　者：李晨娟[1] 韩清华[1] 

机构地区：[1]山西医科大学第一医院心内科,太原030001

出　　处：《中国药学杂志》2009年第2期111-115,共5页Chinese Pharmaceutical Journal

基　　金：2004年山西省资助回国留学人员基金(晋留管办发[2004]7号);2005年山西省科技攻关项目基金(晋科技发[2005]31号051094-5)

摘　　要：目的应用Langendorff离体心脏灌注的方法,观察不同浓度尾加压素II(Urotensin Ⅱ,UII)对正常与心衰大鼠心功能的影响,及特异性的PKA抑制剂(KT5720)对UII作用于大鼠心脏效应的影响,探讨UII作用于心脏的可能机制。方法在langendorff离体心脏灌注的模型上,观察:①UII处理组:给予不同浓度的UII后,正常及心衰大鼠心功能的变化;②KT5720+UII处理组:在灌流KT5720基础上给予UII(IC50),正常与心衰大鼠心功能指标的变化;③KT5720对照组:给予KT5720后正常与心衰大鼠心功能的变化。结果①UII处理组:给予不同浓度的UII(10-10、10-9、10-8和10-7mol·L-1),①灌注正常大鼠心脏后,左心室压最大上升速率(+dp/dtmax)分别降低16.48%、25.53%、31.53%、34.47%,左心室压最大下降速率(-dp/dtmax)分别降低22.78%、33.63%、46.09%、51.73%;②灌注心衰大鼠心脏后,+dp/dtmax分别降低19.01%、26.05%、34.36%、37.27%,-dp/dtmax分别降低27.71%、38.72%、53.41%、60.12%。心衰大鼠的抑制率大于正常大鼠。⑵KT5720+UII处理组:KT5720基础上灌注UII(IC50),①正常大鼠+dp/dtmax降低5.37%,-dp/dtmax降低7.59%;②心衰大鼠+dp/dtmax降低3.27%,-dp/dtmax降低3.15%。+dp/dtmax、-dp/dtmax抑制率与UII组(IC50)比较,均有统计学差异(正常大鼠P<0.01;心衰大鼠P<0.01)。③KT5720对照组:给予KT5720后,①正常大鼠+dp/dtmax降低5.99%,-dp/dtmax降低7.63%;②心衰大鼠+dp/dtmax降低2.84%,-dp/dtmax降低2.96%;与KT5720对照组的±dp/dtmax抑制率比较无统计学差异(正常及心衰大鼠P值均>0.05)。结论UII对正常大鼠及心衰大鼠心脏功能均呈剂量依赖性抑制,KT5720可以阻断UII对大鼠心脏的抑制作用,UII对心功能的抑制作用可能是通过PKA途径起作用。OBJECTIVE To investigate the effect of urotensin Ⅱon cardiac function in normal and heart failure rats. METHODS Hearts were perfused in the Langendorffmode, ①UⅡ group： urotensin Ⅱ （10^-10, 10^-9, 10^-8 and 10^-7 mol·L^-1） was given respectively, cardiac function was measured in healthy and heart failure rats;②KT5720＋UⅡ group： perfused UⅡ（IC50） on the basis of KT5720, observed normal and heart failure rat＇s cardiac function; ③KT5720 group： recorded normal and heart failure rat＇s hemodynamic index after perfused KT5720. RESULTS ①UⅡ group： After given UⅡ（10^-10, 10^-9, 10^-8 and 10^-7 mol·L^-1） in the fluid,① normal rats： ＋dp/dtmax decreased 16.48%, 25.53%, 31.53%and34.47%, -dp/dtmax reduced 22.78%, 33.63%, 46.09% and51.73%; ②heart failure rats： ＋dp/dtmax decreased 19.01%, 26.05%, 34.36%, 37.27%, -dp/dtmax, reduced 27.71%, 38.72%, 53.41%, 60.12%, respectively. The heart failure rats＇ ratio was higher than normal rats＇. ②KT5720＋UⅡ group： urotensin Ⅱ（IC50） was given on the basis of KT5720, ①normal rats： ＋dp/dtmax reduced 5.37%, -dp/dtmax decreased 7.59%; ②heart failure rats： ＋dp/dtmax reduced 3.27%, -dp/dtmax decreased 3.15%. There were significantly differences between KT5700＋UⅡ and UⅡ group in ＋dp/dtmax（nonnal rat and heart failure rat： P〈0.01）; ③KT5720 group： after perfused KT5720, ①normal rats： ＋dp/dtmax decreased 5.99%, -dp/dtmax decreased 7.63%; ②heart failure rats： ＋dp/dtmax decreased 2.84%, -dp/dtmax decreased 2.96%. In normal and heart failure rats, there were no significantly differences between KT5720＋UⅡ group and KT5720 group in ＋dp/dtmax（P〉0.05） . CONCLUSION The inhibitory effect of UⅡon normal and heart failure rat＇s cardiac function was dose dependent, KT5720 could inhibit this effect, so the mechanism of UⅡ on normal and heart failure rat＇s cardiac function was probably mediated by PKA.

关 键 词：尾加压素Ⅱ KT5720 离体心脏 心功能 机制 

分 类 号：R965[医药卫生—药理学]