3/4肾切除并异丙肾皮下注射致慢性心衰合并肾衰模型的制备

目的:研究大鼠3/4肾切除并异丙肾上腺素(ISO)皮下注射致慢性心衰合并肾衰模型的制备.方法:雄性SD大鼠经“两次手术切除法”行3/4肾切除,1周后分成2组,分别皮下注射ISO(70 mg/kg或100 mg/kg,分2次,间隔24 h),对照组给予假手术并注射生理盐水,4周后比较各组大鼠存活率、心衰及肾衰情况.试剂盒法测定血清肌酐、尿素氮,Bradford法测定24 h尿蛋白量,左心室插管术测定左室收缩压(LVSP)、左室舒张压(LVDP)、左室舒张末压(LVEDP)及左室压力最大上升及下降速率(±dp/dtmax).称重法测定心脏重量参数.切片HE染色观测心肌病理情况.结果:对照组大鼠无死亡,大小剂量模型存活率分别为73％、87％,与对照组相比,大小剂量模型组大鼠血清各项指标、尿蛋白明显升高,LVSP下降,LVDP和LVEDP均上升,心脏重量参数比升高,提示左室舒张和收缩功能损伤,发生左室心衰和左室心肌肥厚重构.且大剂量组与小剂量组比较心肾功能差异有统计学意义.结论:3/4肾切除并ISO(100 mg/kg)皮下注射较ISO(70 mg/kg)皮下注射,更易同时诱发大鼠左室心衰及肾衰.     

Preventive effect of naringin on cardiac markers, electrocardiographic patterns and lysosomal hydrolases in normal and isoproterenol-induced myocardial infarction in Wistar rats

Diets rich in natural antioxidants are associated with reduced risk of heart diseases. This study was aimed to evaluate the preventive role of naringin on cardiac troponin T (cTnT), lactate dehydrogenase (LDH)-isoenzyme, cardiac marker enzymes, electrocardiographic (ECG)-patterns and lysosomal enzymes in isoproterenol (ISO)-induced myocardial infarction (MI) in male Wistar rats. Rats subcutaneously injected with ISO (85 mg/kg) at an interval of 24 h for 2 days showed a significant increase in the levels of cTnT, intensity of the bands of LDH-isoenzyme (LDH1 and LDH2) and the activities of cardiac marker enzymes such as creatine kinase-MB (CK-MB), creatine kinase (CK), LDH, aspartate transaminase (AST) and alanine transaminase (ALT) in serum with subsequent decrease in the activities of CK, LDH, AST and ALT in the heart and alterations in ECG-patterns. The activities of lysosomal enzymes (β-glucuronidase, β-N-acetyl glucosaminidase, β-galactosidase, cathepsin-B and cathepsin-D) were increased significantly in serum and the heart of ISO-induced rats, but the activities of β-glucuronidase and cathepsin-D were decreased significantly in the lysosomal fraction of the heart. Pretreatment with naringin (10, 20 or 40 mg/kg) daily for a period of 56 days positively altered the levels of cTnT, intensity of the bands of the LDH1 and LDH2-isoenzyme and the activities of cardiac marker enzymes, ECG-patterns and lysosomal hydrolases in ISO-induced rats. Thus, naringin possess cardioprotective effect in ISO-induced MI in rats.     

Efficacy of grape seed proanthocyanidins on serum and heart tissue lipids in rats subjected to isoproterenol-induced myocardial injury

The present study was aimed to evaluate the preventive role of grape seed proanthocyanidins (GSPs) on serum and tissue lipid enzymes in isoproterenol (ISO)-induced myocardial injury in male Wistar albino rats. GSP was administered orally to rats (150-180 g) in three different doses, by gastric gavage (50, 100 and 150 mg/kg GSP), 6 days a week for 5 weeks. At the end of this period, all the rats, except the normal untreated rats that served as the control group, were administered ISO, 85 mg/kg subcutaneously, for 2 consecutive days to induce myocardial injury. After 48 h, rats (n=6 per group) were anesthetized with anesthetic ether, sacrificed and the levels of biochemical observations of the serum and heart tissues were performed. Biochemical assessment of myocardial injury was done by measuring the activities of serum thiobarbituric acid reactive substances and plasma lactate, which were significantly elevated in the rats administered with ISO. Further, our results suggest that prior administration of GSPs significantly maintained the cholesterol, phospholipids, triglycerides, and free fatty acids levels in serum and heart tissue of the ISO-induced myocardial injury in rats. The experiments conclude that GSPs possess cardioprotective and hypolipidemic effect on the treatment of ISO-induced myocardial injury.     

Increased Basic Fibroblast Growth Factor (bFGF) Accumulation and Distinct Patterns of Localization in Isoproterenol-Induced Cardiomyocyte Injury

Basic FGF is a multifunctional protein which promotes regeneration in several tissues. To investigate involvement in cardiac injury-repair, bFGF accumulation and localization was examined in hearts of rats injected with a single high dose of isoproterenol. The bFGF content of cardiac extracts was analyzed at 6 and 24 hours as well as 1, 4, and 6 weeks by western blotting of heparin-sepharose-bound fractions. The 18 kilodalton bFGF species showed an approximately 2-fold increase in extracts from treated animals compared to non-treated controls. A transient rise in a 21–23 kilodalton bFGF species was seen at 24 hours after treatment. An induction of bFGF mRNA was also observed in treated animals. To localize bFGF in vivo, immunofluorescent labelling with specific antibodies was used at 4–24 hours and 1–4 weeks after treatment. Simultaneous labelling for the cytoskeletal proteins vinculin or vimentin was employed to identify viable myocytes or non-muscle interstitial cells, respectively. Necrotic myocytes, identified by loss of vinculin, displayed a pronounced increase in cytoplasmic anti-bFGF staining compared to adjacent normal myocytes. This increase occurred prior to and may play a role in promoting mobile cell migration and proliferation in areas of necrosis. Viable cardiomyocytes adjacent to fibrotic regions displayed strong pericellular anti-bFGF staining and, occasionally, were also stained by anti-vimentin antibodies, suggesting reexpression of an embryonic phenotype and thus an attempt for regeneration. These data showing increased accumulation and distinct patterns of localization of bFGF in the hearts of isoproterenol-treated animals suggest that this growth factor plays a role in short-term as well as long term response of the myocardium to injury.     

自拟活血通脉灵对心肌缺血大鼠SOD活性和MDA含量的影响

目的探讨活血通脉灵(HXTML)对异丙肾上腺素(ISO)所致心肌缺血大鼠心肌超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量的影响。方法将50只Wistar雄性大鼠随机分为空白对照组、模型组、阿司匹林组及活血通脉灵大剂量治疗组(HXTMLmax)和小剂量治疗组(HXTMLmin),采用ISO复制心肌缺血模型,观察心肌组织中SOD活性和MDA含量的变化。结果与空白对照组比较,模型组SOD活性明显下降,MDA含量增加(P<0.01);与模型组比较,阿司匹林组、HXTMLmax组和HXTMLmin组SOD活性增高、MDA含量降低(P<0.05或P<0.01);与阿司匹林组比较,HXTMLmax组和HXTMLmin组SOD活性升高、MDA含量下降(P<0.05,P<0.01);而HXTMLmax组与HXTMLmin组比较,差异无统计学意义(P>0.05)。结论活血通脉灵能提高心肌缺血损伤大鼠心肌组织中SOD活性,降低MDA含量,具有一定抗心肌氧化损伤作用。     

葡萄糖酸镁灌胃对大鼠异丙肾上腺素心肌损伤的影响

用大鼠异丙肾上腺素心肌损伤模型,研究了葡萄糖酸镁胃内给药的心肌保护作用。结果表明,葡萄糖酸镁胃内给药能减少异丙肾上腺素所致的心肌细胞Mg~(2+)丢失和Ca~(2+)聚积,减轻心肌组织脂质过氧化损害,抑制细胞内乳酸脱氢酶的释放,并能显著地减轻异丙肾上腺素引起的心肌肥大或/和水肿等病理损伤。证实了葡萄糖酸镁胃肠道给药具有一定的心肌保护作用,为其临床应用提供了实验依据。     

Heterogeneity in epithelium-dependent responses

The airway epithelium exerts a profound influence on the responsiveness of bronchial smooth muscle to both contracting and relaxing agents. This may be due to the release of an epithelium-derived factor or factors. There is a considerable heterogeneity in the effects of the epithelium between orders of bronchi, between species, and between pharmacologic agents. Such heterogeneity may reflect variations in the release and/or effect of the epithelium-derived relaxing factor(s). This report demonstrates that: (1) there is a basal and a stimulated release of the factor, (2) the prominence of different types of release varies between species, (3) the effect of the epithelium on relaxation of bronchial smooth muscle is greatest in the presence of high degrees of cholinergic tone, (4) the effects of the epithelium are not mediated via cyclic GMP, and (5) the epithelium-derived relaxing factor is not nitric oxide.     

Effect of isoproterenol and taurine on heart calcium in normal and cardiomyopathic hamsters

Calcium accumulation has been implicated in the cardiac necrosis induced by isoproterenol and in the development of the cardiomyopathy in the BIO 14.6 hamster. Taurine, a natural constituent of the heart, has been shown to exert a modulating effect on calcium levels in the heart. Heart calcium and taurine levels were determined in BIO 14.6 and random bred (F₁B) hamsters treated with isoproterenol (80 mg/kg) following a 60 day drinking regimen of either taurine (100 mmol/l) or guanidinoethyl sulfonate (1%). Taurine supplementation provided some protection for the random bred hamster heart against isoproterenol induced calcium accumulation, but that protection was not demonstrable in the BIO 14.6 strain despite an elevated heart taurine content. The feeding of guanidinoethyl sulfonate decreased the taurine content of the heart in both strains, but guanidinoethyl sulfonate was unable to block taurine elevation following isoproterenol treatment in either strain. Since taurine feeding retards the usual calcium accumulation in the BIO 14.6, but is without statistically significant effect on the additional calcium accumulation induced by isoproterenol, the protecitive action of taurine seems insufficient to counteract the combined effect of isoproterenol and the myopathic process.     

Increased cardiac myosin ATPase activity as a biochemical adaptation to running training: enhanced response to catecholamines and a role for myosin phosphorylation

The effects were studied of prior running training on protein phosphorylation and adenosine triphosphatase (ATPase) activities of natural actomyosin isolated from perfused rat hearts. Myosin Ca²⁺-ATPase activities were significantly higher in running-trained hearts than in controls, whereas the Ca²⁺-stimulated, Mg²⁺-dependent ATPase activities of natural actomyosin were not changed. After treatment of isolated perfused hearts with the β-agonist isoproterenol, both troponin-I and myosin P light chains became phosphorylated. Troponin-I phosphorylation (1 mol/mol) was the same in both sets of hearts and was accompanied by similar changes in cardiac cyclic AMP contents. The V_max values for myosin Ca²⁺-ATPase activity were increased after isoproterenol treatment in all the perfused hearts, but to a significantly greater extent in the hearts of running trained animals; this was correlated with enhancement of both the rate and extent of myosin P light chain phosphorylation. Enhanced Ca²⁺-dependent myosin P light chain phosphorylation, further enhanced by β-adrenergic stimulation, represents, at the molecular level, a biochemical response to running training.     

The effects of trimetoquinol on the intact rabbit heart and myocardial adenylate cyclase activity: evidence for spare myocardial beta receptors

We have compared and contrasted the actions of (-)isoproterenol and (+/-) trimetoquinol on rabbit heart preparations. In the presence of either GTP or Gpp[NH]p (guanosine-5'-(beta, gamma imino) triphosphate), trimetoquinol displayed partial agonist activity in stimulating adenylate cyclase activity in a particulate rabbit heart preparation. Trimetoquinol enhanced adenylate cyclase activity 20% or 65% of the maximum obtainable by isoproterenol in the presence of GTP or Gpp[NH]p respectively. In the presence of GTP, concentrations of catecholamines required to enhance cyclase activity 15% of the maximum obtainable with isoproterenol (EC15) were 2.0 X 10(-7) M and 5.5 X 10(-8) M for trimetoquinol and isoproterenol, respectively. In the presence of Gpp[NH]p EC30 values were 2.0 X 10(-7) and 3.5 X 10(-8) M for trimetoquinol and isoproterenol respectively. Trimetoquinol also displayed partial agonist activity for the ability to increase cAMP levels in the isolated perfused rabbit heart. By contrast trimetoquinol was equieffective to isoproterenol at increasing tension development and rate of contraction of the isolated perfused heart. Concentrations of catecholamines required to increase tension and rate of contraction 50% of the maximum obtainable with isoproterenol were 1.5 X 10(-7) M and 1.7 X 10(-8) M for trimetoquinol and isoproterenol, respectively. These data show that only a partial stimulation of adenylate cyclase activity and cAMP levels by trimetoquinol is sufficient to produce maximal changes in mechanical activity of the heart.(ABSTRACT TRUNCATED AT 250 WORDS)