【作者】 李晨娟；

【导师】 韩清华；

【作者基本信息】 山西医科大学 ， 心血管内科， 2008， 硕士

【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。方法应用腹主动脉缩窄法建立大鼠心衰模型。在langendorff离体心脏灌注的模型上,观察:⑴UII处理组:给予不同浓度的U II后,正常及心衰大鼠心功能的变化;⑵KT5720+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;⑶KT5720对照组:给予KT5720后正常与心衰大鼠心功能的变化。结果⑴UII处理组:给予不同浓度的U II (10^-10、10^-9、10^-8和10^-7 mol﹒L^-1) ,①灌注正常大鼠心脏后,左心室压最大上升速率(+dp/dt_max)分别降低16.48%、25.53%、31.53%、34.47% ,左心室压最大下降速率(-dp/dt_max)分别降低22.78%、33.63%、46.09%、51.73%;②灌注心衰大鼠心脏后, +dp/dt_max分别降低19.01%、26.05%、34.36%、37.27%,-dp/dt_max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:灌流KT5720基础上,①正常大鼠:给予UII（10-7 mol﹒L -1, >IC50）+dp/dt_max降低5.37%,-dp/dt_max降低7.59%;②心衰大鼠:给予UII(10^-8 mol﹒L^-1, >IC50) +dp/dt_max降低3.27%,-dp/dt_max降低3.15%。+dp/dt_max、-dp/dt_max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）。⑶KT5720对照组:给予KT5720后,①正常大鼠+dp/dt_max降低5.99%,-dp/dt_max降低7.63%;②心衰大鼠+dp/dt_max降低2.84%,-dp/dt_max降低2.96%;与KT5720对照组的±dp/dt_max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。更多还原

【Abstract】 AIM To investigate the effect and signaling mechanism of urotensin II on cardiac function in normal and heart failure rats.Methods Hearts were perfused in the Langendorff mode,⑴UII group: Urotensin II （10-10、10-9、10-8 and 10-7 mol﹒L-1） was given respectively perfusion , then investigated the normal and heart failure rat’s cardiac function;⑵KT5720+UII group : perfused UII（ IC50 ） on the basis of KT5720 , observed normal and heart failure rat’s cardiac function ;⑶KT5720 group : recorded normal and heart failure rat’s hemodynamic index after perfused KT5720.Results⑴UII group: After given UII (10^-10、10^-9、10^-8 and 10^-7 mol﹒L^-1) in the fluid ,①normal rats : +dp/dt_max decreased 16.48%、25.53%、31.53% and 34.47%, -dp/dt_max reduced 22.78%、33.63%、46.09% and 51.73%;②heart failure rats : +dp/dt_max decreased 19.01%、26.05%、34.36%、37.27%, -dp/dt_max reduced 27.71%、38.72%、53.41%、60.12%, respectively. The heart failure rats’ratio was higher than normal rats’.⑵KT5720+UII group : urotensin II( IC₅₀ ) was given on the basis of KT5720 ,①normal rats : +dp/dt_max reduced 5.37%, -dp/dt_max decreased 7.59%;②heart failure rats : +dp/dt_max reduced 3.27%, -dp/dt_max decreased 3.15%. There were significantly differences between KT5700+UII and UII group in±dp/dt_max（normal rat and heart failure rat: P<0.01）⑶KT5720 group : after perfused KT5720 ,①normal rats: +dp/dt_max decreased 5.99%, -dp/dt_max decreased 7.63%;②heart failure rats : +dp/dt_max decreased 2.84%, -dp/dt_max decreased 2.96%. In normal and heart failure rats , there were no significantly differences between KT5720+UII group and KT5720 group in±dp/dt_max, （P>0.05） .Conclusions The inhibitory effect of UII on 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.更多还原