真武汤合苓桂术甘汤改善心肾综合征大鼠模型水钠潴留的作用机制研究

[目的]研究真武汤合苓桂术甘汤对心肾综合征大鼠模型水钠潴留的作用机制。[方法]将60只雄性SD大鼠随机分为两组,即空白组与手术组,空白组大鼠常规饲养,手术组大鼠经5/6肾切除联合异丙肾上腺素皮下注射制备心肾综合征模型,剔除死亡大鼠后,将手术组剩余成模大鼠按体质量分层随机分为空白组、中药组、常规治疗组。中药组给予真武汤合苓桂术甘汤灌胃,给药量为7.29 g生药/(kg·d);常规治疗组给予贝那普利(0.45 mg/kg)+呋塞米(1.8m g/kg);空白组予以等容积生理盐水灌胃,每日1次,连续6周。观察实验过程中各组大鼠的精神状态、活动情况、灵敏度、毛发情况、食欲、大小便等一般情况及死亡情况,比较各组灌胃前、灌胃6周后的血清脑钠肽(BNP)、血肌酐(Scr)、血尿素氮(BUN)、尿水通道蛋白2(AQP2)的前后差值情况。[结果]灌胃6周后,中药组大鼠一般情况较灌胃前改善、喘息不明显,常规治疗组一般情况同样较灌胃前改善。通过比较治疗前后各组大鼠实验室指标差值发现,中药组与常规治疗组BNP均下降,中药改善大鼠心力衰竭情况接近常规治疗组水平,两组下降水平无统计学差异(P0.05);中药组Scr水平较前下降,常规治疗组Scr水平升高;中药组尿AQP2水平较前略增高,与空白组尿AQP2水平无统计学差异(P0.05),常规治疗组尿AQP2水平较前明显升高。[结论]心肾综合征大鼠尿AQP2的表达主要由肾脏调控,AQP2可作为心肾综合征水钠潴留状态的参考指标,真武汤合苓桂术甘汤改善心肾综合征大鼠水钠潴留状态的作用机制可能是通过抑制大鼠肾脏AQP2过度表达,减少水的重吸收,改善了水钠潴留状态。     

Neurotransmitter-Mediated Changes in the Electrophysiological Properties of Pituicytes

Intracellular recordings were obtained from pituicytes in the neural lobe of the isolated rat pituitary. Like other glia, pituicytes lacked action potentials in response to depolarizing current injection, but they tended to have more positive resting membrane potentials and higher input resistances than astrocytes in other preparations. Dye-coupling typical of astrocytes was also demonstrated amongst pituicytes, and their morphologies were similar to those of pituicytes stained for glial fibrillary acidic protein. Action potentials, anode-break spikes or barium spikes were not observed in pituicytes, even under conditions that maximized the elicitation of Ca²⁺-dependent responses. This suggests that pituicytes either have no or a very low density of Ca²⁺ channels or Ca²⁺ currents that are too small to generate action potentials. Dynorphin A (1–13), a kappa-opioid agonist, produced long-lasting increases in pituicyte input resistance with no significant changes in resting membrane potential. Dynorphin's action was concentration-dependent and was blocked by the opioid antagonist naloxone. This is consistent with previous reports demonstrating kappa-opioid receptors on pituicytes in the neurohypophysis. The β-adrenergic agonist isoproterenol (100 μM) reversed the increases in pituicyte input resistance produced by opioid application, with no significant changes in resting membrane potential. The fact that pituicytes responded to neurotransmitters suggests a functional link between pituicytes and neurosecretory nerve fibres.     

蒲黄对大白鼠心律失常的预防作用

蒲黄水提物腹腔注射(5g生药/kg)大白鼠,预防异丙肾上腺素引起的心室纤颤和猝死,以及氯化钡恒速灌注引起的心律失常,结果表明蒲黄水提物能显著地提高动物的存活率,并明显地增加导至动物心律失常而致死的氯化钡剂量。     

The effect of an isoprenaline infusion on the splenic blood flow and intrasplenic platelet kinetics

The effect of a constant isoprenaline infusion on the venous platelet count, splenic blood flow and intrasplenic platelet kinetics was investigated in 6 healthy male volunteers. The study was carried out using autologous 111In-labelled platelets and dynamic gamma camera imaging of the initial distribution of radiolabelled platelets between blood and splenic platelet pool. The isoprenaline infusions were administered i.v. over 30 min in a dose of 0.03 micrograms/kg/min. These infusions significantly increased the splenic blood flow and the size of the exchangeable splenic platelet pool. Concomitantly, there was a decrease of labelled as well as unlabelled platelets in the peripheral blood. The intrasplenic platelet transit time was not affected. Before start of infusion, the splenic blood flow was 6.1 +/- 2.9 (SD) % of total blood volume/min and the splenic platelet pool size 34 +/- 9 (SD) %. During infusion the corresponding values were 8.7 +/- 3.9 (SD) and 41 +/- 11 (SD), respectively. It is concluded that an i.v. infusion of isoprenaline enhances splenic pooling of platelets as a result of an increase in splenic blood flow.     

西红花酸对异丙肾上腺素致大鼠急性心肌缺血损伤的保护作用

目的 研究西红花酸对异丙肾上腺素(ISO)致大鼠急性心肌缺血的保护作用及机制。方法 采用大剂量ISOsc诱导产生大鼠急性心肌缺血模型(1SO30mg／kg，每日一次，连续2d)，实验大鼠随机分为正常组、ISO模型组、阳性对照组和3个西红花酸给药组(25，50，100mg／kg)，测定心脏系数和血清中乳酸脱氢酶(LDH)、磷酸肌酸激酶(CK)和丙二醛(MDA)含量，观察心肌组织谷肮甘肤过氧化物酶(GSH—Px)、Na^ ，K^ —ATP酶和Ca^2 ，Mg^2 —ATP酶活性及心脏病理改变，观察西红花酸的保护作用。结果 西红花酸能显著降低血清中CK和LDH的释放；也能显著降低血清和心脏匀浆中MDA水平，心脏重量参数显示对心肌水肿有明显的抑制作用；保护心肌GSH—Px；Na^ ，K^ —ATP酶和Ca^2 ，M8^2 -ATP酶活性，心脏病理切片表明西红花酿对心肌坏死有显著的保护作用。结论 西红花酸对ISO所致急性心肌缺血有显著的保护作用。     

Effects of the C-terminal Peptide of the αs subunit of the G protein on the regulation of Adenylyl Cyclase and Protein Kinase A activities by Biogenic Amines and Glucagon in Mollusk and Rat Muscles

The C-terminal parts of the subunits of heteromeric G proteins play an important role in the functional linkage of G proteins with receptors of the serpentine type. The present report describes studies of the effects of the C-terminal octapeptide 387–394 of the _s subunit of the mammalian G protein on the transmission of the hormonal signal via the hormone-sensitive adenylyl cyclase signal system, whose major components are receptors of the serpentine type, G proteins, and the enzymes adenylyl cyclase and protein kinase A. The peptide synthesized here, 387–394 amide (10^–7 - 10^–4 M), dose-dependently decreased adenylyl cyclase and protein kinase A activities stimulated by serotonin and glucagon in smooth muscle from the freshwater bivalve mollusk Anodonta cygnea and by the agonist isoproterenol in rat skeletal muscle. At a concentration as low as 10^–7 M, the peptide released potentiation of the stimulatory effects of hormones on adenylyl cyclase activity due to the non-hydrolyzable guanine nucleotide analog Gpp[NH]p. At the same time, it had almost no effect on the stimulation of adenylyl cyclase activity by non-hormonal agents (NaF, Gpp[NH]p, and forskolin). The inhibitory effects of hormones on adenylyl cyclase and protein kinase A activities persisted in the presence of the peptide. Our data demonstrate the importance of the C-terminal part of the _s subunit of the stimulatory G protein for its functional linkage with receptors of the serpentine type and throw light on the molecular mechanisms of the interactions between G proteins and receptors.Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 89, No. 7, pp. 837–850, July, 2003.     

β3‐Adrenoceptors modulate left ventricular relaxation in the rat heart via the NO‐cGMP‐PKG pathway

Aims: Using a model of isolated and Langendorff‐perfused rat heart we analysed whether activation of β₃‐adrenergic receptors (β₃‐ARs) influences ventricular lusitropic performance. We also focused on the NOS/NO/cGMP/PKG cascade as the signal transduction mechanism. Methods: Hearts were treated with increasing concentrations (from 10^?12 to 10^?6 m ) of BRL₃₇₃₄₄, a selective β₃‐AR agonist, and cardiac performance was evaluated by analysing both lusitropic parameters and coronary motility. Cardiac preparations were also perfused with BRL₃₇₃₄₄ in the presence of either isoproterenol (ISO) or nadolol, or pertussis toxin (PTx), or selective inhibitors of the NOS/NO/cGMP/PKG pathway. Results: BRL₃₇₃₄₄ caused a significant concentration‐dependent reduction in (LVdP/dt)_min, a decrease in half time relaxation significant starting from 10^?12 m , and an increase in (LVdP/dt)_max/(LVdP/dt)_min ratio (T/?t). BRL₃₇₃₄₄ abolished the ISO‐mediated positive lusitropism. β₃‐AR‐dependent effects on relaxation were insensitive to β₁/β₂‐AR inhibition by nadolol (100 nm ), and were abolished by G_i/o protein inhibition by PTx (0.01 nm ). NO scavenging by haemoglobin (10 μm ), and nitric oxide synthase (NOS) inhibition by NG‐monomethyl‐l ‐arginine (10 μm ) revealed the involvement of NO signalling in BRL₃₇₃₄₄ response. Pre‐treatment with inhibitors of either soluble guanylate cyclase (ODQ; 10 μm ) or PKG (KT₅₈₂₃; 100 nm ) abolished β₃‐AR‐dependent negative lusitropism. In contrast, anantin (10 nm ), an inhibitor of particulate guanylate cyclase, did not modify the effect of BRL₃₇₃₄₄ on relaxation. Conclusion: Taken together, our findings provide functional evidence for β₃‐AR modulation of ventricular relaxation in the rat heart which involves PTx‐sensitive inhibitory Gi protein and occurs via an NO‐cGMP‐PKG cascade. Whether the effects of β₃‐AR stimulation on lusitropism are beneficial or detrimental remains to be established.     

活血通脉片对大鼠异丙肾上腺素心肌损伤的保护作用

目的：研究中药复方制剂活血通脉片（Huoxue TOngmai tablet,HXTMT)对异丙肾上腺素（isoproterenol,ISO)心肌损伤大鼠的保护作用,方法：用HXTMT给SD大鼠连续灌胃14d,第12日起动物sc ISO(48umol.kg^-1.d^-1),每日一次,连续3d,复制异丙肾上腺素性心肌损伤大鼠模型。结果：中药复方制剂HXTMT能明显减轻心肌损伤程度,血清CK活性,心肌MDA含量,心肌含水量分别减少14％,25％,2％,与模型组比较有显性差异（P＜0．05）,结论：HXTMT能稳定细胞膜,减轻心肌水肿程度,阻止脂质过氧化物的形成,提示HXTMT对心肌缺血性损伤有细胞保护作用。