大鼠慢性应激性水浸溃疡模型的复制

本文复制了慢性、应激性水浸溃疡模型,23℃每天拘束水浸4小时,4天后所得溃疡病变明显,溃疡指数是13.8士4.5mm~2,且再现性良好,是一个较好的慢性、应激性溃疡模型。哌哌西平对此溃疡具有较强的防治作用。     

Effects of the atypical antidopaminergic drug,metoclopramide and the selective antimuscarinic drug,pirenzepine on neurotransmission

Metoclopramide is equipotent to chlorpromazine in a number of biochemical and behavioural tests which measure antidopaminergic effects. In spite of the extensive use of metoclopramide for gastrointestinal disturbances and as an antiemetic, it is not usually prescribed for psychiatric indications. The present study, using neuroendocrine and receptor technics, shows that in addition to its antidopaminergic effects metoclopramide has atypical effects on neurotransmission. Thus, metoclopramide increases growth hormone secretion which is usually decreased by neuroleptic drugs, and also tends to increase plasma noradrenaline levels. The discrepancies between the receptor affinities of benzamides in vitro and their effects in vivo are also discussed, as well as the selective antimuscarinic action of pirenzepine on metoclopramide-induced hormonal effects.     

哌仑西平对兔急性心肌缺血心率变异与心电生理的影响

观察小剂量哌仑西平对兔急性心肌缺血时心率变异 (HRV)与心电生理的影响 ,为临床应用提供实验理论依据。建立兔急性心肌缺血模型 ,采用HRV的时域指标及频域指标测定心肌缺血时心脏自主神经功能 ,应用心电生理研究方法测定心肌缺血时的心室有效不应期 (VERP)、VERP离散度 (VERPD)、QT间期离散度 (QTd)、心室颤动阈值 (VFT)的变化 ,比较哌仑西平预处理组与对照组各项指标。结果 :兔急性心肌缺血时 ,与对照组比较 ,哌仑西平预处理组HRV时域指标RR间期 (2 85 .6± 16 .3vs 2 5 0 .9± 8.4ms)、SDNN(6 .0± 2 .6vs 3.9± 0 .9ms)、rMSSD(6 .3± 1.3vs 4.8± 0 .9u)、CV(% ) (2 .6± 0 .33vs 1.9± 0 .19)、HRVI(9.5± 1.8vs 5 .9± 1.0u)均增高 (P <0 .0 5 ) ;频域指标VLF(0 .12 5± 0 .0 16vs 0 .19± 0 .0 17ms2 )、LF(0 .46± 0 .0 3vs 0 .5 2± 0 .0 4ms2 )、LF/HF(0 .14± 0 .0 0 5vs 0 .34± 0 .0 12 )均降低(P <0 .0 5 ) ,HF(3.2± 0 .16vs 2 .1± 0 .12ms2 )增高 (P <0 .0 1) ;心电生理指标VERPD(14.4± 4.2vs 2 1.2 5± 5 .2ms)及QTd(2 9± 8vs 2 6± 9ms)降低 (P <0 .0 5 ) ,VFT(36 .5± 7.9vs 2 3.8± 7.4mA)增高 (P <0 .0 5 )。相关性分析显示HRV指标与VFT相关。结论 :小剂量哌仑西平预处理能改?     

盐酸哌仑西平在水溶液中的降解动力学

目的:研究盐酸哌仑西平(pirenzepine hydrochloride,PRZ)在水溶液中的降解动力学.方法:采用经典恒温法进行试验,通过高效液相色谱法(HPLC法)检测PRZ的浓度.结果:PRZ在水溶液中的水解为伪一级动力学反应,同时受H 和OH-催化,酸催化速率常数(K1)为0.595 h-1*mol-1*L,碱催化速率常数(K2)为4.67×103 h-1*mol-1*L,K2是K1的7 849倍,表明PRZ在水溶液中主要受OH-催化水解.PRZ在水溶液中的最稳定pH(pHm)为5.1.PRZ在pH 1.1、pH 5.1、pH 7.0和pH 10.0(I=0.3)的水解反应活化能(Ea)分别是72.83、105.10、74.33和71.67(KJ/mol),在室温(25 ℃)下的有效期(t0.9)分别为13.1,783.6,58.2和0.7 d;在pH 1.1的水溶液中PRZ表观水解速率常数随离子强度(I)的增加而增大;相反,在pH 7.9的水溶液中,PRZ表观水解速率常数随离子强度增加而降低.结论:PRZ在强酸和强碱条件下均不稳定,若制成液体制剂可调pH为5.1左右.     

An embryonic chick pancreas organ culture model: characterization and neural control of exocrine release

An embryonic chick (Gallus domesticus) whole-organ pancreas culture system was developed for use as an in vitro model to study cholinergic regulation of exocrine pancreatic function. The culture system was examined for characteristic exocrine function and viability by measuring enzyme release, and noting histological, morphological, and anti-amylase immuno-fluorescence staining changes over a series of incubation times. This embryonic culture system exhibits loss of viability and morphological degeneration after 12 h of incubation time. Characterization and development of this exocrine model system was an important aspect of this study. Assessment of the 18-day-old embryonic chick pancreas model clearly indicated biochemical and cholinergic functionality, and morphological integrity, of the tissue after 4-h incubation. This embryonic age and incubation period were utilized for all subsequent cholinergic studies. The in vitro model was used to study parasympathetic regulation of exocrine function via the muscarinc receptors present in the embryonic chick pancreas. The effects of synthetic muscarinic agonists (bethanechol and carbachol) and subtype-specific antagonists affected amylase release to varying degrees suggesting heterogeneity of receptors. The effects of the muscarinic receptor antagonists atropine (non-specific), pirenzepine (M(1)-selective) and 4-DAMP [4-diphenylacetoxy-N-methyl-piperidine methiodide] (M(3)-selective) on bethanechol-stimulated amylase release were examined. Atropine and 4-DAMP at concentrations of 2 microM and higher significantly inhibited (p<0.05) agonist-stimulated amylase release, while pirenzipine did not at 2 microM, but did at 200 microM. The M(3) subtype selective antagonist 4-DAMP (2 pM-2 mM) significantly inhibited (p<0.05) 5 mM bethanechol-stimulated amylase release at concentrations of 2 microM and greater (amylase activity decreased from 100.61 to 49.41 U/l/mg). The data suggest the existence of a muscarinic receptor subtype for the embryonic chick pancreas exocrine cells characteristic to the mammalian M(3) glandular subtype.     

反相高效液相色谱法测定哌吡酮中间体

本文用反相高效液相色谱法研究了哌吡酮中间体5,6-二氢-6-氧代-11-氯乙酰基吡啶骈[2,3—b][1,4]苯骈二氮杂(Ⅰ),5,6-二氢-6-氧代-11H-吡啶骈[2,3-b][1,4]苯骈二氮杂(Ⅱ)及2-氯-3-(2-氨基苯甲酰胺基)吡啶(Ⅲ)的测定方法。以micro PakMCH-5,150×4.6mm I.D.为色谱柱,甲醇-水(48∶52)为流动相,254nm紫外检测波长,氢氯噻嗪为内标,由内标法和内标单点校正法完成了各中间体的测定。两法叫吸率的平均值为100.2%(Ⅰ),102.3%(Ⅱ)和100.0%(Ⅲ),相关系数为0.9977(Ⅰ),0.9977(Ⅱ)和0.9998(Ⅲ)。     

哌仑西平促进豚鼠巩膜成纤维细胞分泌胶原及增殖的细胞内信号转导机制

目的探讨哌仑西平促进豚鼠巩膜成纤维细胞（GSF）分泌胶原及增殖的细胞内信号转导机制。方法体外培养GSF,采用免疫细胞化学染色法及羟脯氨酸测定法分别观察不同浓度哌仑西平溶液（1％、2％、3％、5％）作用下,GSF中Smad3、CTGF、Ⅰ型胶原表达量的变化和GSF培养上清中胶原含量的变化。结果在1％、2％、3％、5％浓度的哌仑西平溶液作用下,GSF中Smad3、CTGF、Ⅰ型胶原表达量明显增强;GSF培养上清中胶原含量均较对照组明显增加。哌仑西平的最小有效质量浓度是1％,在1％-5％浓度范围内,哌仑西平可促进GSF中Smad3、CTGF、Ⅰ型胶原表达量增强,3％哌仑西平溶液的促增强作用最强,但与5％的哌仑西平无显著差别。结论哌仑西平具有促进GSF分泌胶原和增殖的作用,其作用可能是通过smad3-CTGF信号转导通路实现的。     

Salivation from the denervated human parotid gland induced by pirenzepine and telenzepine

Summary In the denervated human parotid gland the non-classical cholinolytic agents pirenzepine and telenzepine induce a similar paradoxical salivatory response to that of atropine, scopolamine and metacine.     

Cholinergic and GABAergic mediations of the effects of apomorphine on serotonin neurons.

Apomorphine (APO) has been shown to elevate tryptophan, serotonin (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) concentrations in the dorsal raphe (DR) and its corresponding projection site, the striatum, but not in the median raphe (MR) and its terminal area, the hippocampus. We have previously demonstrated that these effects are indirectly mediated through dopamine (DA) autoreceptors in the substantia nigra and possibly gamma-aminobutyric acid (GABA) neurons in or near the DR. In the present study, we have further found that the effects of APO on 5-HT neurons are also mediated through both nicotinic and M1 muscarinic cholinergic receptors as well as GABAA receptors in the DR. This suggestion is based on the findings that both atropine and mecamylamine antagonized the effects of APO, while carbachol at a high dose exerted an effect opposite to that of APO. Besides, pirenzepine and bicuculline at low doses also antagonized, whereas saclofen did not alter the influence of APO on 5-HT in the striatum. Bicuculline at a higher dose enhanced tryptophan and 5-HT measures by itself. None of the drugs studied had a significant effect on tryptophan, 5-HT, or 5-HIAA in the hippocampus. These results together suggest that DA, ACh, and GABA neurons are all involved in the actions of APO on 5-HT, while the direct synaptic relationships among these neurotransmitters and the precise anatomical locus for these interactions to occur are still unknown. It is possible that APO, by inhibiting DA neuron firing in the substantia nigra and through the GABA disinhibition mechanism, therefore indirectly activates 5-HT neurons in the DR and the striatum. While the above neuronal firing model well explains the elevation of 5-HIAA, the simultaneous increases of tryptophan and 5-HT, especially tryptophan, may be more readily explained by a mechanism of tryptophan uptake upon APO administration. Further anatomical, biochemical, and electrophysiological studies are ongoing to test this hypothesis and to clarify the circuit and the anatomical locus (loci) for these interactions to occur.