大鼠下丘脑微量注射TRH对心功能的作用及其机制

EFFECTS AND MECHANISM OF HYPOTHALAMIC TRH ON CARDIAC FUNCTION IN RATS

目的:探讨下丘脑促甲状腺激素释放激素(TRH)对心功能活动的调节作用及其作用机制。方法:在SD大鼠下丘脑促垂体区埋管,微量注射TRH或预先注射一氧化氮合酶抑制剂L-NAME及M型乙酰胆碱受体阻断剂阿托品,记录给药前后左心室内压峰值(LVSP)、心率(HR)、室内压瞬时上升速率峰值(dp/dtmax)和瞬时下降速率峰值(-dp/dtmax)。结果:①与对照组相比,下丘脑促垂体区注射TRH可引起LVSP、HR、dp/dtmax及-dp/dtmax显著升高(P<0.05或P<0.01)。②单独注射L-NAME后只引起LVSP显著升高(P<0.05或P<0.01),L-NAME预处理可抑制TRH引起的正向调节效应。③单独注射阿托品引起LVSP及dp/dtmax的显著升高(P<0.05),HR显著下降(P<0.05),阿托品预处理减弱了TRH加快心率和提高-dp/dtmax的效应。结论:①下丘脑TRH对心脏有正性变时、变力作用。②下丘脑内源性NO能降低LVSP,但对HR、dp/dtmax及-dp/dtmax无明显影响,TRH的作用是经NO依赖通路的。③下丘脑内源性胆碱能递质对心脏有正性变时但负性变力的作用,下丘脑TRH调节心功能可能部分通过胆碱能M受体通路。

Aim： To investigate the effect of hypothalamic thyrotropin-releasing hormone （TRH） on cardiac function and its mechanism. Methods： The Sprague-Dawley rats were mounted in a stereotaxic apparatus and a guide cannula placed in the left hypophysiotrophic area, through which TRH were microinjected in presence or absence of L-NAME and atropine. The left ventricular systolic pressure （LVSP）, heart rate （HR） and the maximum velocity of ascending or descending in intraventricular pressure （ ± dp/dtmax ） were recorded. Results： ① TRH microinjected into the hypophysiotrophic area induced a significant increase of LVSP, HR, dp/dtmax and- dp/dtmax （P〈0.05, P〈0.01）. ② L-NAME significant increased LVSP and pretreatment with L-NAME inhibited the positive effects induced by TRH. ③ Atropine increased LVSP and dp/dtmax（ P〈 0.05）, but it significantly descended heart rate（ P 〈 0.05）. Pretreatment with atropine weakened the tachycardiac response induced by TRH. Conclusion： ① Hypothalamic TRH can produce positive inotropic and chronotropic response to myocardium.② Hypothalamic endogenous NO can descend LVSP, but has no effects on HR, dp/dtmax and-dp/dtmax. The effect of TRH is through nitric oxide-dependent pathway. ③ Hypothalamic endogenous cholinergic transmitter can produce negative chronotropic and positive inotropic response to myocardittm. Hypothalamic TRH mediates cardiac function maybe partly through cholinergic M receptor.