免疫缺陷裸鼠无创性心肌缺血缺氧损伤模型的构建

目的：通过对免疫缺陷裸小鼠腹腔注射异丙肾上腺素，构建一种无创性裸小鼠的心肌缺血缺氧损伤模型。方法：16只免疫缺陷裸小鼠随机分为3组：对照组5只，实验A组7只，实验B组4只，其中实验A、B组连续3d重复腹腔注射5mg／kg异丙肾上腺素，对照组则注射等量生理盐水。对照组和实验A组于第3次注射后24h处死，实验B组则于第3次注射后2周处死。各组裸小鼠处死前取血清进行心肌酶检测，心脏标本称重，常规HE染色。结果：实验A组、B组、对照组的心脏质量分别为（94．97±6．12）mg、（79．35±7．63）mg、（81．38±10．11）mg，A组相对于B组、对照组，差异均具有统计学意义（P〈0．01）。HE染色显示A组局部心肌组织损伤与变性坏死，而B组病变程度明显较轻，未见斑痕形成。实验A组、B组、对照组的乳酸脱氢酶（LDH）分别为（6662．70±884．78）U／L、（4096．75±448．75）U／L、（4419．40±880．50）U／L，A组相对于B组、对照组，差异均具有统计学意义（P〈0．01）。结论：腹腔反复大剂量注射异丙肾上腺素可构建免疫力缺陷裸小鼠的心肌缺血缺氧损伤模型。     

俞原配穴针刺对慢性心肌缺血大鼠的保护作用及其机制研究

目的 探讨俞原配穴针刺对慢性心肌缺血大鼠的保护作用及其机制.方法 48只Wistar大鼠随机分成对照组、模型组、配穴组、单穴组各12只,除对照组外每组大鼠注射盐酸异丙肾上腺素建立慢性心肌缺血模型.造模成功后,配穴组给予针刺神门、大陵、心俞、厥阴俞穴,单穴组仅针刺内关穴,对照组与模型组不作处理.比较各组大鼠左心室收缩压(LVSP)、左心室舒张末期压(LVEDP)、左室压上升最大速率(+dp/dtmax)、左室压下降最大速率(-dp/dtmax)、心率等心功能指标,观察各组大鼠血清超氧化物歧化酶(SOD)、丙二醛(MDA)、脂质过氧化物(LPO)、谷胱甘肽过氧化物酶(GSH-PX)水平及心肌梗死面积的变化.结果 干预15 d后,与模型组比较,配穴组大鼠的LVSP、+dp/dtmax、-dp/dtmax、心率、SOD、GSH-PX水平较高,MDA、LPO、LVEDP较低(均P<0.05);与单穴组比较,配穴组LVSP、+dp/dtmax、-dp/dtmax SOD、GSH-PX水平较高,LPO水平较低(均P<0.05);配穴组心肌梗死面积小于模型组及单穴组(均P<0.05).结论 俞原配穴针刺对慢性心肌缺血大鼠具有保护作用,其作用机制可能与俞原配穴针刺降低脂质过氧化损伤、减轻心肌受损程度有关.     

异丙肾上腺素诱导的心功能不全中自噬的变化

目的 探讨在异丙肾上腺素诱导的心功能不全中自噬的变化。方法 用异丙肾上腺素腹腔注射法建立小鼠心功能不全模型;小动物超声影像系统检测心功能指标射血分数（ejection fraction,EF）、左室缩短率（fractional short,FS）、舒张早期充盈峰值/房缩期充盈峰值（ratio of early peak flow velocity and atrium peak flow velocity,E/A）和室间隔厚度（interventricular septum,IVS）的变化;尾压法间接检测血流动力学指标——心率（heart rate,HR）、收缩压（systolic blood pressure,SBP）、舒张压（diastolic blood pressure,DBP）和平均动脉压（mean blood pressure,MBP）的变化;心质量体质量比法即心脏质量（heart weight,HW）/体质量（body weight,BW）检测心脏质量指数的变化;Western blotting印迹法检测心脏组织中自噬标志物LC3、p62的变化。结果 与对照组相比,异丙肾上腺素模型组在4周后,小鼠心功能下降,EF下降、FS下降、IVS增加,差异具有统计学意义;同时模型组小鼠HR和DBP低于对照组,差异具有统计学意义;心脏质量指数指标（HW/BW）显示模型组较对照组增高;自噬标志物检测显示,异丙肾上腺素注射1 d和3 d后,LC3Ⅱ/LC3Ⅰ比值升高,p62蛋白的相对量降低;连续注射4周后,LC3Ⅱ/LC3Ⅰ比值与p62蛋白的相对量恢复至对照组水平。结论 异丙肾上腺素诱导的心功能不全过程中,心肌自噬早期升高,晚期恢复至正常水平。     

冠心康抗心肌缺血的实验观察

目的：观察冠心病对缺血心肌的保护作用。方法：采用常压耐缺氧小鼠存活时间，夹闭小鼠气管心电消失时间，垂体后叶素和异丙肾上腺素引起大鼠心肌缺血等方法。结果：不同剂量的冠心康能延长缺氧小鼠存活时间，并能改变缺血心肌的心电图，与生理盐水比较差异有显著性（Ｐ〈０．０１）。结论：冠心康对心肌缺血有保护作用。     

左旋精氨酸通过激活L-arg-NO通路对异丙肾上腺素致大鼠心力衰竭的作用

目的 探究左旋精氨酸( L-arg)通过激活L-arg-NO通路对异丙肾上腺素( ISO)导致的大鼠心力衰竭的保护作用.方法 雄性SD大鼠随机分为对照组、ISO组、L-arg干预组.腹腔注射ISO复制大鼠心力衰竭模型,灌胃给予L-arg. 30 d后监测血流动力学参数:心率( HR)、左室收缩压力( LVSP)、左室舒张末期压力( LVEDP )、左室压力最大上升或下降速率( ± dp/dtmax ) ,计算心肺系数,检测血清超氧化物歧化酶( SOD)、肿瘤坏死因子-α( TNF-α)、一氧化氮( NO)含量以及一氧化氮合酶( NOS)活性;HE染色观察心肌组细胞排列;Masson染色观察心肌胶原纤维并计算心肌胶原纤维容积分数( CVF). 结果 与对照组比较,ISO组大鼠血流动力学参数:HR、LVSP、+dp/dtmax降低,LVEDP、-dp/dtmax升高,心肺系数增加,血清TNF-α、SOD升高, NO、NOS降低,差异均有统计学意义(P<0. 05). L-arg干预组HR、LVSP、+dp/dtmax均高于ISO组,LVEDP、-dp/dtmax、心肺系数低于ISO组,血清SOD和TNF-α降低,NO和NOS增加,差异均有统计学意义(P<0. 05). HE染色显示对照组心肌细胞形态正常,间质无扩张充血,心肌细胞排列整齐;ISO组心肌细胞排列紊乱,炎性细胞浸润,而 L-arg 干预组心肌细胞接近对照组.ISO组Masson染色心肌细胞间可见大量蓝染的胶原纤维,而对照组观察不到蓝染区域, L-arg干预组在对照组与ISO组之间;ISO组CVF明显高于L-arg干预组(P<0. 05),L-arg干预组高于对照组( P<0. 05 ). 结论 L-arg可以通过激活L-arg-NO通路,增加机体内 NO 含量,改善血流,减轻心肌重构,产生对心力衰竭心肌的保护作用.     

两种异黄酮衍生物对小鼠心肌营养血流的影响

异黄酮衍生物MHDF和MHPF是我所合成的、对心血管系统具有广泛作用的化合物。本实验用小鼠尾静脉注射同位素^86Rb示踪法，测得MHDF和MHPF对正常活动小鼠的心肌营养血流无明显影响。但能对抗β受激动剂异丙肾上素所致心肌营养血流的改变。基作用强度比特异性抗剂普萘洛尔稍弱。在垂体后叶素所致心肌缺血模型上，MHDF能明显增强心肌营养血流，与硝酸甘油的作用相似。提示，MHDF对收缩的血管平滑肌有较强的舒张效应。MHDF和MHPF在整体动物中都不能对抗CaCl对心肌营养血流所造成的改变。     

Genetic differences in the resistance of rats to isoprenaline-induced heart lesions

Summary Two strains of rats were obtained by selective breeding: the IR strain, resistant to isoprenaline-induced myocardial lesions and the IS strain, sensitive to this damage.The IR rats grew more slowly, the weight of their adipose tissue was higher and the weight of m. soleus was less than that of the IS rats.The IR rats had a higher content of triglycerides in the serum and a lower isoprenaline-stimulated lipolytic activity of adipose tissue in vitro. The basal NEFA level in the serum and its rise after the administration of isoprenaline in vivo did not differ between the strains.The IR rats had a higher content of glycogen in the heart and in the muscle. After the administration of isoprenaline the glycogen content decreased more slowly in IR rats.The findings indicate a considerable importance of the glycogen stores in the heart for the resistance of myocardium to damage.     

CARDIAC INTERACTION BETWEEN PARATHYROID HORMONE, β-ADRENOCEPTOR AGENTS, AND VERAPAMIL IN THE GUINEA-PIG IN VITRO

1. The present study examines the modulation, by parathyroid hormone, of the changes in myocardial contractile force induced by isoprenaline, propranolol isomers, verapamil, and nadolol. 2. Cardiac contractile force was estimated by the use of guinea-pig isolated auricles. Synthetic bovine 1-34 parathyroid hormone (sPTH) alone did not modify contractile force; conversely, sPTH significantly inhibited the cardiode-pressant effect of l-propranolol, d, l-propranolol, d-propranolol, and verapamil. These results suggested an action of sPTH independent of β-adrenoceptors. Against an hypothesis of a single, non-β-adrenoceptor mechanism of sPTH action on the heart are the following observations: (i) when β-adrenoceptors were blocked with nadolol, sPTH no longer inhibited the cardiodepressant effect of propranolol, (ii) sPTH reduced the inotropic effects of isoprenaline. Our conclusion, therefore, is that sPTH probably affects cardiac muscle contraction by at least two mechanisms, one of which involves non-adrenergic transmembrane calcium flux and the second β-adrenoceptors. 3. When these studies were extended into the clinical pharmacological field, it was found that plasma ultrafiltrates from severely hyperparathyroid patients in chronic renal failure inhibited like sPTH the cardiodepressant action of propranolol. No such effect was seen with ultrafiltrates from parathyroidectomized patients. Accordingly, high PTH levels may inhibit the action of cardiotropic drugs administered to hyperparathyroid patients, and may be one factor in the cardiomyopathy seen in such patients.     

The effect of norepinephrine, isoprenaline and acetylcholine on the testicular and epididymal circulation in the pig

Blood flow to the testis and epididymis of 7 anaesthetized male pigs was measured using electromagnetic blood flow sensors. An average blood flow to the testis of 12 ml/min/100 g and in the epididymal arteries of 19 ml/min/100 g was measured. The effect of intravenously administered norepinephrine, isoprenaline and acetylcholine on α and β₂ adrenergic and cholinergic receptor sites, respectively, was investigated. As neither norepinephrine nor isoprenaline, nor acetylcholine changed vascular conductance of the testis, we could not demonstrate adrenergic and cholinergic receptor activity. The possibility of autonomic regulation by the nonvascular smooth muscles of the spermatic cord and the inner layer of the tunica albuginea has been discussed.