牛黄降压丸治疗高血压随机平行对照研究

摘要：[目的]观察牛黄降压丸治疗高血压疗效。[方法]使用随机平行对照方法,将104例住院患者按随机数字表分为两组。对照组52例复方利血平氨苯蝶啶片,20mg/次,1次／d。治疗组52例牛黄降压丸,9g／次,2次／d。连续治疗30d为1疗程。观测临床症状、血压、不良反应。连续治疗2疗程（60d）,判定疗效。[结果始疗组显效28例,有效19例,无效5例,总有效率90．38％。对照组显效20例,有效16例,无效16例,总有效率69．23％。治疗组疗效优于对照组（P〈0．01）。两组血压均有改善（P〈0．05）,治疗组改善优于对照组（P〈0．05,P〈0．01）。[结论]牛黄降压丸治疗高血压效果显著,值得推广。     

液相色谱质谱联用(LC-MS/MS)在天然化学成分分析中的应用Ⅰ.音喷离子化(SSI)与大气压化学离子化(APCI)对利血平的比较分析

报道应用 L C- MS/ MS,采用音喷离子化 (SSI)与大气压化学离子化 (APCI)对利血平的比较分析 ,应用这两种离子化方法比较所得的利血平的标准质谱 (MS)和二级质谱 (MS2 ) ,实验证明两种离子化方法所得结果完全一致     

儿茶酚胺耗竭后蟾蜍心脏的形态学观察

利血平5～10mg/kg剂量作耗竭CA试验时,蟾蜍心肌纤维间嗜铬样细胞胞质棕黄色明显变浅;交感神经末梢未见显示,仅心外膜或血管周围显示少量,表明CA基本耗竭。利血平为50mg/kg时,CA安全耗竭,即均无交感神经末梢出现,嗜铬样细胞的胞质仅隐约可见。     

Down-regulation of serotonin2, but not of beta-adrenergic receptors during chronic treatment with amitriptyline is independent of stimulation of serotonin2 and beta-adrenergic receptors

Antidepressant drugs down-regulate beta-adrenergic, alpha₂-adrenergic and serotonergic 5-HT₂ receptors with a time course that parallels their clinical efficacy, i.e. chronic administration is required (Crews and Smith, 1978; Svensson and Usdin, 1978; Banerjee, Kung, Riggi and Chanda, 1979; Bergstrom and Keller, 1979; Peroutka and Snyder, 1980). In the present study, it was found that the 5-HT₂ receptor antagonist, nefazadone (50 mg/kg per day) did not prevent the downregulation of 5-HT₂ receptors in the cerebral cortex produced by amitriptyline (10 mg/kg per day), when administered for 3 weeks. Moreover, treatment with nefazadone (50 mg/kg per day) alone for 3 weeks decreased binding to 5-HT₂ receptors in cerebral cortex. In contrast, administration of propranolol, the beta receptor antagonist, (10 mg/kg per day) with amitriptyline (10 mg/kg per day) for 3 weeks prevented the down-regulation of beta receptors, but did not alter the decrease in binding to 5-HT₂ receptors. In addition, the depletion of central stores of norepinephrine and serotonin by a 4-day treatment with reserpine (5 mg/kg per day) increased binding to beta receptors in the cerebral cortex and hippocampus, but did not affect binding to 5-HT₂ receptors in either region. These results suggest that the 5-HT₂ receptor is not down-regulated by direct stimulation by serotonin agonists and that the down-regulation of 5-HT₂ receptors by amitriptyline is independent of down-regulation of beta-adrenergic receptors.     

A marked rise in 5-S-cysteinyl-dopamine levels in guinea-pig striatum following reserpine treatment

Summary Reserpine administration (5 mg/kg, i.p.) to guinea pigs resulted in marked and long lasting dopamine (DA) depletion and a rapid, short lasting, increase of 3,4-dihydroxyphenylacetic acid (DOPAC) in the striatum. A marked and sustained increase of the level of 5-S-cysteinyl-dopamine, which is an adduct presumably formed following autoxidation of DA, started 3–4 h following the DA and DOPAC changes. Only small changes in the levels of the 5-S-cysteinyl adducts of DOPAC and 3,4-dihydroxyphenylalanine (DOPA) were found.     

EFFECTS OF RESERPINE PRETREATMENT ON NEUROEFFECTOR TRANSMISSION IN THE VAS DEFERENS

1. The effects of reserpine pretreatment on neurotransmission in the guinea-pig vas deferens have been re-examined with a view to study the role of noradrenaline (NA) in mediating postjunctional electrical responses and, in particular, excitatory junction potentials (EJP). 2. Reserpine (5 mg/kg, i.p.) caused almost total depletion (below detection levels) of the NA content of the vas deferens. However, spontaneous and evoked excitatory junction potentials (SEJP, EJP) and currents (SEJC, EJC) could still be recorded in NA-depleted tissues. The amplitude distribution of SEJC in control and reserpinized tissues was similar. 3. Facilitation of EJP and EJC was markedly slowed in reserpinized tissues, EJP taking 50-60 pulses to facilitate fully. However the amplitudes of fully facilitated EJP were comparable to EJP recorded in control tissues. 4. EJPs in reserpinized vasa deferentia were unaffected by the NA synthesis inhibitor, alpha-methyl tyrosine, but were abolished in the presence of the stable ATP analogue alpha,beta-methylene ATP which desensitizes postjunctional P2-purinoceptors. 5. Local application of ATP, but not NA, mimicked the EJP. These results indicate that EJP are mediated by a non-noradrenergic neurotransmitter possibly ATP.     

Motor actions of eliprodil in the normal and monoamine-depleted mouse: A role in the treatment of Parkinson's disease?

Summary The non-competitive NMDA polyamine site antagonist, eliprodil, was examined for its effects on exploratory activity in non-habituated mice and for its antiakinetic potential in reserpine-treated mice. A low dose of eliprodil (5 mg/kg) weakly stimulated locomotion in naive animals, whilst higher doses depressed rearing (20–40 mg/kg) and grooming (40 mg/kg), consistent with a sedative action. At no dose did eliprodil cause ataxia. In 24h reserpine-treated mice, eliprodil (10–40 mg/kg) reversed akinesia, but this effect was subject to considerable inter-animal variation and was not statistically significant. Eliprodil did not alter the motor recovery elicited by the dopamine D₁ agonist SKF 38393, or the dopamine D₂ agonist RU 24213, and suppressed the motor stimulation induced by L-DOPA. These results indicate that eliprodil displays a far lower propensity than many other NMDA receptor antagonists for disturbing posture and gait, but lacks the essential motor stimulant action required to make it a safe and effective antiparkinsonian agent, at least in the reserpine-treated mouse model of Parkinson's disease,     

Effects of sex steroids on growth hormone responses to clonidine and GHRH in reserpine pretreated rats

Summary Administration of reserpine in a dose causing depletion of brain monoamines led to a complete suppression of the pulsatile secretory pattern of growth hormone (GH) in gonadectomized (GX) as well as in sham-operated male and female rats. In GX animals of both sexes treated with estradiol, but not in those treated with testosterone or dihydrotestosterone (DHT), the reserpine induced inhibition of GH release was partially antagonized. Administration of the alpha₂-adrenoceptor agonist clonidine caused secretion of GH in reserpine pretreated, sham-operated rats. In GX male rats GH responses to clonidine were blunted, while in GX males treated with testosterone or estradiol, but not in those treated with DHT, the responses were restored. In female rats gonadectomy did not significantly affect the GH releasing effect of clonidine. However, administration of estradiol to GX females led to enhanced responses to the alpha₂-agonist. Administration of the GH releasing hormone (GHRH) induced pronounced GH secretion in reserpine pretreated animals of both sexes; this effect was not significantly affected by gonadectomy. In GX males, however, GH responses to GHRH were enhanced by replacement with estradiol or testosterone, while in GX females, estradiol, but not testosterone, had the same effect.     

基于动物物质与能量代谢检测评价3种肾阴虚证模型建立方法

目的:通过对动物物质与能量代谢相关指标的检测,比较3种肾阴虚证动物模型的科学性与可靠性。方法:40只小鼠按照体质量均衡原则分为正常组、氢化可的松组、甲状腺素联合利血平组及热性中药组,每组10只。正常组每天给予生理盐水灌胃,氢化可的松组隔日皮下注射氢化可的松50 mg·kg~(-1),甲状腺素联合利血平组灌胃甲状腺素150mg·kg-1加肌肉注射利血平1 mg·kg~(-1),热性中药组灌胃热性中药煎煮液按生药量为15 g·kg~(-1),建立3种肾阴虚证模型小鼠。分别观察动物采食量、饮水量、体质量、自主活动情况、呼吸耗氧量、体温、体能耐力、血清环磷酸腺苷(cyclic adenosine monophosphate,cAMP)与环磷酸鸟苷(cyclic guanosine monophosphate,cGMP)及其比值等指标,考察3种肾阴虚证模型小鼠体质及自身能量代谢的差异。结果:造模后3种肾阴虚证模型小鼠饮水量与饮食量均增加,体质量均降低。此外,氢化可的松组小鼠呼吸耗氧量降低、四肢体温及肛温明显升高,cAMP/cGMP比值明显升高,与正常组比较,有显著性差异(P0.05)。自主活动、体能耐力及肾脏系数变化不明显,与正常组比较,无显著性差异;甲状腺素联合利血平组小鼠肾脏系数、单位时间耗氧量与正常组比较,明显降低,自主活动及体能耐力及有降低趋势,但与正常组比较,无显著性差异。四肢体温、肛温及血清cAMP与cGMP水平明显升高,与正常组比较,有显著性差异(P0.05);热性中药组小鼠单位时间耗氧量明显降低,自主活动次数增加,与正常组比较,有显著性差异,肾脏系数、四肢体温、肛温、体能耐力及血清cAMP与cGMP水平及其比值变化均不明显,与正常组比较,无显著性差异。结论:皮下注射氢化可的松、灌胃甲状腺素联合肌肉注射利血平混悬液可在短时间内建立肾阴虚证模型小鼠,灌胃热性中药在短时间内无法成功建立肾阴虚证模型小鼠。     

Simulation of outward transport of neuronal 3H-noradrenaline with the help of a two-compartment model

Summary In order to simulate the outward transport of ³H-noradrenaline induced by veratridine from adrenergic varicosities, a mathematical two-compartment model was developed in which the two compartments (representing axoplasm and storage vesicles) are arranged in series. Simulated results were compared with experimental results obtained with 100 mol/l veratridine + 1 mmol/l ouabain and rat vasa deferentia kept in calcium-free solution (Bönisch and Trendelenburg 1987). As in experiments, the time course of efflux of ³H-noradrenaline had a pronounced and early peak under RPU-conditions, a minor peak under PU-conditions, and solely a plateau under U-conditions (where R stands for pretreatment with reserpine, P for pretreatment with pargyline, and U for inhibition of COMT by U-0521). From the width of the peak of release, it was deduced that — under RPU-conditions — about 40% of neuronal ³H-noradrenaline are distributed into the axoplasm, about 60% into the storage vesicle. However, this estimate represents an average value; the results are compatible with the view that the ratio axoplasmic/vesicular ³H-noradrenaline is quite variable from rat to rat. Under U-conditions, calculations confirm that reserpinelike compounds induce an efflux of tritium that consists predominantly of deaminated ³H-metabolites. The stimulation of outward transport, on the other hand, causes an efflux of tritium that consists predominantly of ³H-noradrenaline; indeed, the efflux of deaminated ³H-metabolites declines (as it did in experiments). Simulations showed further that the highest rates of outward transport of ³H-noradrenaline were achieved when there was a simultaneous induction of outward transport of ³H-noradrenaline and a reserpine-like effect (as it is known to occur when tissues are exposed to veratridine; Bönisch and Trendelenburg 1987). While there was satisfactory agreement between simulated and experimental results under various conditions, there were also two discrepancies that may be caused by a) inhomogeneous labelling of the storage vesicles in individual varicosities (RPU < PU < U) and b) saturation of outward transport of ³H-noradrenaline when a reserpine-like compound greatly increases the axoplasmic level of total noradrenaline (under U-conditions).Abbreviations COMT catechol-O-methyl transferase - DOMA dihydroxymandelic acid - DOPEG dihydroxyphenylglycol - FRL fractional rate of loss - MAO monoamine oxidase Supported by the Deutsche Forschunesgemeinschaft (SFB 176) Send offprint requests to E. Schömig