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。     

β-Adrenergic agonists suppress chronic/relapsing experimental allergic encephalomyelitis (CREAE) in Lewis rats

Chronic/relapsing experimental allergic encephalomyelitis (CREAE) serves as an animal model for relapsing/remitting multiple sclerosis. Treatment with the β-adrenergic agonist isoproterenol or the β₂-adrenergic agonist terbutaline significantly suppressed both the first acute attack and the number of relapses in CREAE Lewis rats. The number of relapses was decreased even when treatment with β-adrenergic agonist was started after the onset of the first acute attack of CREAE. β-adrenergic receptor number was increased significantly on splenocytes from CREAE rats as compared to healthy controls or CFA-injected rats. Terbutaline treatment of CREAE rats lowered the splenocyte receptor number to normal values.     

Changes in myocardial pyrimidine nucleotide levels following repeated injections of isoproterenol in rats

Changes which might lead to the initiation of cardiac hypertrophy include possible variations in the dynamics of nucleotides. In the experiments reported in this paper, changes in the pool sizes of adenine, uracil and cytosine nucleotides were observed during the initial phase of cardiac overload.Repeated subcutaneous injections of isoproterenol (ISO) (5 mg·kg^–1 body weight, s.c.) were performed so as to produce symmetric cardiomegaly in rats. Under these conditions, the dry weight of the heart, on the fifth day of dialy injections of ISO, had increased by 43% and the RNA concentration by 39%. There was no significant change in the DNA concentration. No further changes in weight or in DNA and RNA concentrations were recorded from the fifth to the tenth day of treatment.Changes in UTP and ATP were carefully monitored during the first days following ISO application. The levels of both nucleotides decreased sharply at first. The ATP level remained below the control value for at least 48 h while the UTP level was rapidly restored and a further increase occurred resulting in a maximal enlargement of 82% after the 12th h. At the same time, the uracil nucleotide pool and the cytosine nucleotide pool had increased by 76% and 101%, respectively, while the adenine nucleotide content of the myocardium remained 15% below control level. Repeated injections of ISO induced effects on ATP and UTP levels which were similar in direction but attenuated.The significance of an increase in the pyrimidine nucleotide pools in relation to nucleic acid synthesis is discussed.     

白术多糖对小鼠淋巴细胞功能的调节

研究了白术多糖ＰＡＭ体内及体外对小鼠脾淋巴细胞的调节作用。结果表明：白术多糖ＰＡＭ在一定的浓度范围内能单独激活或协同ＣｏｎＡ／ＰＨＡ促进正常小鼠淋巴细胞转化并能明显提高ＩＬ－２分泌的水平。ＰＡＭ对氢化可的松造成的免疫抑制小鼠淋巴细胞的增殖功能有恢复作用。同时还发现白术多糖ＰＡＭ对淋巴细胞的调节与β－肾上腺素受体激动剂异丙肾上腺素相关。     

异丙肾上腺素ISP致心肌微血管阻塞的机理探讨

本实验通过对血浆凝固性的动态变化和自由基系统有关指标的变化的监测以及心肌组织病理学观察发现,大鼠皮下注射大剂量异丙肾上腺素(ISP)(85mg/kg)后早期(4h以前)即有明显的血浆高凝状态、内源性凝血系统激活和心肌微血管内血栓形成,且心肌缺血损伤程度与血浆凝固性紊乱程度之间呈正直线相关;心、肝、肾和脑以及血清MDA含量显著增加(P<0.01),心肌的SOD和GSH—Px活性均显著增高。提示ISP引起的膜脂质过氧化、血浆高凝状态以及由此而引发的血管内皮受损和微血栓形成是ISP致心肌微血管阻塞的重要机理。     

Cardioprotective activity of Ginkgo biloba Phytosomes in isoproterenol-induced myocardial necrosis in rats: A biochemical and histoarchitectural evaluation

The protective effects of Ginkgo biloba Phytosomes (GBP) in isoproterenol (ISO)-induced cardiotoxicity and the antioxidant activity involved in this protection were investigated in rats. Myocardial infarction was produced in rats with 65, 85, 120 and 200mg/kg of ISO administered subcutaneously (sc) twice at an interval of 24h. An ISO dose of 85mg/kg was selected for the present study as this dose offered significant alteration in biochemical parameters and moderate necrosis in heart. Effect of GBP oral treatment for 21 days at two doses (100mg and 200mg/kg body weight) was evaluated against ISO (85mg/kg, sc)-induced cardiac necrosis. Levels of marker enzymes (AST, LDH and CPK) were assessed in serum and heart, antioxidant parameters viz., reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) and malondialdehde (MDA) were assayed in heart homogenate. Significant myocardial necrosis, depletion of endogenous antioxidants and increase in serum levels of marker enzymes were observed in ISO-treated animals when compared with the normal animals. GBP elicited a significant cardioprotective activity by lowering the levels of serum marker enzymes and lipid peroxidation and elevated the levels of GSH, SOD, CAT, GPx and GR. The present findings have demonstrated that the cardioprotective effects of GBP in ISO-induced oxidative damage may be due to an augmentation of the endogenous antioxidants and inhibition of lipid peroxidation of membrane.     

大鼠心肌细胞胞浆和核Ca2+震荡现象及其机制探讨

目的:在培养的新生大鼠心肌细胞上,观察多种刺激因素对细胞胞浆Ca²⁺([Ca²⁺]c)和核Ca²⁺([Ca²⁺]n)的影响,探讨其时间和空间关系及其机制。方法:以Fluo-4/AM荧光指示剂负载培养的心肌细胞,应用激光共聚焦扫描显微镜检测胞浆和核Ca²⁺震荡的变化。结果:正常心肌细胞内核Ca²⁺的荧光强度高于核周与细胞浆,三者均存在小幅度的钙震荡,分别加入去甲肾上腺素(10^-5mol/L)、异丙肾上腺素(10^-4mol/L)和三磷酸腺苷(ATP3×10^-3mol/L),均使心肌细胞钙震荡幅度明显升高(P＜0.01),L-型Ca²⁺通道阻滞剂维拉帕米(verapamil5×10^-4mol/L)、Ca²⁺-ATPase抑制剂thapsigargin(10^-6mol/L)和KCl(20mmol/L)使钙的周期性震荡消失。用thapsigargin10^-6mol/L预先阻断心肌细胞钙库的Ca²⁺摄取,去甲肾上腺素(10^-5mol/L)则不能引起钙震荡和荧光强度增加。结论:心肌细胞胞浆和核Ca²⁺均能产生钙震荡,而钙震荡的维持则依赖于细胞外Ca²⁺的内流、胞内钙库的Ca²⁺摄取和释放以及正常膜电位的维持。核与胞浆Ca²⁺变化不一致,提示细胞核上可能存在相对独立的Ca²⁺调节系统。     

Influence of isoproterenol on plasma immunoreactive atrial natriuretic peptide and plasma vasopressin in the anesthetized rabbit

Changes in levels of plasma immunoreactive atrial natriuretic peptide (IR-ANP) were measured in response to administration of isoproterenol in the anesthetized, vagotomized rabbit. A dose-dependent increase in plasma IR-ANP was seen in response to 10 min isoproterenol infusions between 0.1 and 10.0 g/kg/min. The time course of these responses showed the maximum levels of IR-ANP to be attained 10 min after the cessation of infusion. In rabbits in which plasma vasopressin (AVP) levels were also measured, the maximum levels of AVP were attained during the infusion period. There was no correlation between levels of AVP and IR-ANP suggesting that AVP released into the plasma did not affect directly the release of IR-ANP. The changes in IR-ANP in response to isoproterenol were significantly reduced in rabbits which had been administered the beta-1-adrenoceptor blocking agent, atenolol. In six rabbits in which the vagi remained intact, the increases in IR-ANP were reduced and became significant only with 10 g/kg/min isoproterenol infusion. The results demonstrate that isoproterenol infusion increases the level of plasma IR-ANP in the anesthetized rabbit and suggest that this is through an effect on the heart rather than on peripheral vessels.     

Effects of β-adrenoceptor stimulation on intracellular Ca transients and tension in rat ventricular muscle

Effects of -adrenoceptor stimulation on intracellular Ca²⁺ transients and tension were explored in rat ventricular muscles injected with aequorin. Adrenaline (0.05–5.0 M) and isoproterenol (0.05–1.0 M) increased the peak of twitch tension and accelerated relaxation. The former effect depended on Ca²⁺ concentration in Tyrode's solution ([Ca²⁺]_o) and the stage of the experiment. Low concentrations of these drugs added to normal Tyrode's solution containing 2 mM [Ca²⁺]_o did not potentiate twitch tension in the early stage of the experiments. These drugs increased the peak of the aequorin light signal and slightly accelerated the falling phase of the light especially the tail. Effects of dibutyryl-cyclic AMP (DB-cAMP) (0.1–5.0 mM) and 3-isobutyl-1-methylxanthine (IBMX) (0.01–0.5 mM) were qualitatively similar to those of adrenaline and isoproterenol.Isoproterenol applied at the peak of Na-deficient contracture decreased tension without significantly changing the light signal; similar results were obtained in the presence of ryanodine (1 M).The results were interpreted as follows: The increase of intracellular cAMP induced by -adrenoceptor stimulation facilitated Ca²⁺ uptake by sarcoplasmic reticulum (SR) and decreased Ca²⁺ sensitivity of contractile elements. Faster relaxation induced by cAMP was considered to be due to the decrease of Ca²⁺ sensitivity of contractile elements and faster Ca²⁺ uptake by SR. The slightly faster falling phase of light transient might be due to the faster Ca²⁺ uptake by SR, which predominates over the slower fall of [Ca²⁺]_i induced by the decreased Ca²⁺ sensitivity of the contractile element.     

Hypotension and thirst in rats after isoproterenol treatment

Drinking induced in rats by systemic isoproterenol treatment is markedly attenuated after bilateral nephrectomy. The present experiments demonstrate that the hypotension produced by iso-proterenol treatment was more profound, and lasted much longer, in nephrectomized rats than in intact animals. When arterial blood pressure was partially elevated by central administration of angiotensin II or carbachol (Experiment 1) or by intraarterial infusion of epinephrine (Experiment 2), drinking behavior was restored in the nephrectomized animals and their water intakes approximated the amounts consumed by intact rats given isoproterenol. In general, an inverted U-shaped curve was found to define the relation between blood pressure and water intake in rats after isoproterenol treatment. Drinking was most probable when mean arterial blood pressures were in the range of 70–85 mm Hg, whereas rats were unlikely to drink when blood pressures were much below or above this range. These findings indicate that isoproterenol-induced thirst is not dependent on a renal dipsogen, and suggest instead that the hypersecretion of renin that occurs in intact rats is simply permissive of drinking behavior by modulating the hypotensive effects of the drug treatment.