【作者】 陶卫国；

【导师】 傅向阳； 李公信；

【作者基本信息】 第一军医大学 ， 心血管内科， 2004， 硕士

【摘要】 目的：探讨热负荷对动物模型慢性心力衰竭血流动力学的影响及其可能机制。 方法：实验分两部分。第一部分：热负荷对动物慢性心力衰竭血流动力学的影响的实验研究。此部分分为两个实验：1．热负荷对动物慢性心力衰竭血流动力学的影响。15只新西兰兔冠状动脉结扎建立慢性心衰模型，随机分为热负荷组(n=5)、对照组(n=5)、假手术组(n=5)，8周后测定其血流动力学变化，然后将热负荷组动物放置在42℃高温仓中，待肛温达到42℃，维持15～20min，热负荷结束后，将动物移置到常温环境下，分别测定热负荷终止后的2、4、8、24h的血流动力学变化情况。2．观察热负荷对动物慢性心力衰竭血浆HSP70与血流动力学的关系。10只新西兰兔作冠状动脉结扎(CAL)，另外5只仅作开胸，不作结扎。冠脉结扎8周后，10只兔随机分为对照组(n=5)和热负荷组(n=5)，并测定血流动力学、血浆HSP70浓度。然后将热负荷组动物放置在环境温度42℃，待肛温达到42℃，维持15～20min，热负荷结束后，将动物移置到常温环境下，分别测定热负荷终止后的2、4、8、24h的血流动力学及血浆HSP70浓度。第二部分：热负荷保护作用的细胞信号转导机制研究。25只新西兰兔作冠状动脉结扎(CAL)，另外5只仅作开胸，不作结扎。冠脉结扎8周后，25只兔随机分为对照组(n=5)热负荷组(n=5)，热负荷+左旋硝基精氨酸甲酯(L-NAME)组(n=5)，常温+L-NAME组(n=5)，常温十左旋精氨酸(L一Arg)组(n=5).并测定血流动力学、血浆NOS、。GMP浓度。将心衰动物放置在环境温度42℃，待肛温达到42℃，维持巧一20min，热负荷结束后，将动物移置到常温环境下，分别测定热负荷终止后的2、4、8、24h的血流动力学及血浆NOS、eGMPO 结果:第一部分:1.所有手术组动物8周后血流动力学与假手术组血流动力学相比出现恶化。2.热负荷组24h后与对照组相比，HR、LVEDP出现明显降低，+dp/d tmax有显著增加。3.结扎8周后心衰组血浆HSP70浓度高于开胸组高。4.热负荷慢性心衰24h后血浆HSP70比对照组、热负荷前都有显著升高。第二部分:1.所有手术组动物血流动力学与假手术组血流动力学相比也出现同样恶化。2.热负荷组24h后血流动力学与对照组比较有改善作用;热负荷+L一NAME组血流动力学与对照组比较无改善作用;常温+L一Arg组血流动力学与对照组比较有改善。3.手术组8周后血浆NOS、cGMP比假手术组高。4.热负荷慢性心衰24h后血浆NOS、cGMP比对照组、热负荷前显著升高，常温组+L一Arg血浆NOS、cGMP高于对照组。 结论:热负荷对动物慢性心力衰竭有保护作用，主要表现在改善血流动力学，升高血浆HSP7O等方面，通过分析我们推断血流动力学的改善与升高的HSP7O有关，其次热负荷直接作用血管使血液重新分布，降低了心脏的前后负荷。热负荷慢性心衰能明显提高NOS\cGMP血浆浓度，cGMP在热负荷慢性心衰有重要意义，它是NOS发挥作用重要中介物质.热负荷改善动物慢性心力衰竭血流动力学机制之一，热负荷激活NOS一NO一cGMP信号转导通路。另外在本次实验中，我们发现动物出现慢性心衰后机体有大量NOS、cGMP表达，他们的生成在一定程度上缓解心 一6-衰症状。更多还原

【Abstract】 Objective:The Observe influence about heat stress on animals of chronic heart failure hemodynamic and their mechanism.Method:The experiment consisted of two parts.The first part:the observe heat stress on animal of chronic heart failure hemodynamic.This part included two experiments:1.observe influence of heat stress on animal of chronic heart failure hemodynamic. 15 New Zealand rabbits coyonary artery ligated leads to chronic heart failure,they were randomly divided into 3 groups :heat stress group,normal temperature group and sham group,examinating hemodynamic variation after eight weeks, and then animals of heat stress group were laid in high temperature room(42?), till rectal temperature of animals is 42 centigrade and they were maintained 15~ 20 minutes,animals of heart failure were diverted to normal temperature environment after heat stress finish and examination hemodynamic variation at 2.4.8.24 hour .2.To observe relationship between plasm heat shock protein 70 and hemodynamic after heat stress on animal of chronic heart failure. 10 Zew Zealand rabbits coronary artery were ligated ,5 rabbits coronary artery were not ligated but chest was operated open.After coronary artery ligated 8 weeks, 10 rabbits were randomly divided into normal temperature group(n=5) and heat stress group(n=5), and examination hemodynamic and plasm heat shock protein(HSP70) concentration.Animals of HS group are exposed thermal enviroment(42癈),they are maintained 15~20 minutes till their rectal temperature is 42 centigrade,animals of HS group are diverted normal temperature environment after HS finish,separately examination hemodynamic and plasm HSP70 concentration at 2,4% 8 , 24 hour .The second part:investigation of mechanism of signal transduction during heat stress protective function.25 New Zealand rabbits coronary artery are ligated, 5 rabbits coronary artery were not ligated ,but chest was operated open.After coronary artery ligated eight weeks ,25 rabbits are randomly divided into 5 groups:normal group(n=5),HS group(n=5), HS and NG-nitro-L.arginine methylester(L-NAME)group(n=5),normal temperature and L-NAMEgroup(n=5), normal temperature and left arginine (L-Arg)group(n=5). Determining hemodynamic and dection plasm of nitric oxide synthsise(NOS) and cyclic guanosine monophosphate (cGMP) concentration.Animals of HS are laid hyperthmia environment(42), they are maintained 15~20 minutes till their rectal temperature is 42 centigrade, animals of HS group are placed normal temperature environment after HS finish,separately examination hemodynamic and plasm NOS and cGMP concentration at 2 4,8, 24 hour .Result:The first part: 1 .Compared with hemodynamic worse in all operation groups and sham group after eight weeks.2.Compared with heart rate,left ventricular end diastolic pressure(LVEDP) decrease significantly in HS group and normal temperature group after heat exposure 24 hour.+dp/dtmax increased significantly.3.Compared with plasm HSP70 concentration of operation group is more higher than sham group after eight weeks.4.HSP70 concentration of HS group is more increaser than normal temperature group and HS ago after heat stress on CHF 24 hr.The second part: 1. Compared with hemodynamic worse in all operation groups and sham group after eight weeks.2.Compared with hemodynamic improvement significantly in HS group and normal temperature group after heat exposure 24 hr;there is not variation about hemodynamic of HS and L-NAME group and normal temperature group after heat stress;Hemodynamic of normal and L-Arg group is improvement than normal temperature group. 3.Plasm NOS and cGMP concentration of CHF animals are higher than sham groupACompared with NOS and cGMP increased significantly in HS CHF group than normal temperature group and HS ago after HS 24 hr,NOS and cGMP concentration of normal and L-Arg group is higher than normal temperature group.Conclusiomthere is protective function about heat stress on animals of CHF,chief show hemodynamic of CHF is improvement ,plasm HSP70 concentration is augument and so on, by analysis w更多还原