干酪菌发酵产物对小鼠小肠推进功能的影响

目的观察干酪菌发酵产物对小鼠小肠推进功能的影响。方法采用小鼠小肠推进实验观察经胃给予干酪菌发酵产物前后小肠推进百分比的变化以及腹腔注射几种受体阻断剂后对其药效的影响。结果干酪菌发酵产物 ( 1 50、30 0、6 0 0mg kg)能提高小鼠小肠推进百分比 ,且呈剂量 效应依赖关系 ;苯海拉明 ( 1 0mg kg)能抑制其对小肠运动的促进作用 ;阿托品 ( 1 0mg kg)能部分对抗其药效。结论干酪菌发酵产物能提高小鼠小肠推进功能 ;其作用途径与H1 受体有关 ,可能与M受体有间接关系。     

二苯氰胂对毒蕈碱性受体的抑制作用

目的研究了日本在我国遗弃的化学武器———二苯氰胂(DC)对离体豚鼠回肠纵肌和毒蕈碱性受体的作用机制,为评估DC的毒理学作用及其对环境的影响提供依据。方法取豚鼠8只,分离豚鼠回肠纵肌16条,分4组,用累积给药法,从低到高分别给予不同浓度的DC,记录离体豚鼠回肠纵肌收缩的幅度,求出DC作用于离体回肠纵肌的EC50值,并通过DC与乙酰胆碱(AChR)的相互作用,研究DC的作用机制。在放射性配体-受体结合实验中,从10只大鼠大脑中提取受体,通过DC与[3H]QNB的竞争结合作用,研究了DC对毒蕈碱性受体的作用。结果DC可抑制离体豚鼠回肠纵肌的收缩作用,其对离体豚鼠回肠纵肌的EC50值为(7.335±2.377)×10-7mol/L,AChR可收缩离体豚鼠回肠,并可反转DC引起离体豚鼠回肠纵肌的舒张作用。在放射性配体-受体结合实验中,DC与毒蕈碱性受体结合的Ki值为(9.19±1.52)nmol/L,IC50值为(16.00±2.65)nmol/L。结论DC可作用于mAChR受体上,初步断定为AChR的拮抗剂。     

呋喃硝胺的药理作用及临床应用

呋喃硝胺(Ranitidine)是继甲氰咪胍(cimetidine)之后,又一个高效的H_2—受体阻断剂。本文将其药理作用及临床应用作一概述。一、动物药理学研究 1.H_2-受体阻断作用呋喃硝胺能抑制组织胺对离体大鼠子宫肌及离体豚鼠心房     

连钱草乙醇提取物对豚鼠离体肠平滑肌和小鼠肠运动功能的影响

目的:观察连钱草乙醇提取物对小鼠小肠推进运动、药物性腹泻小鼠模型和豚鼠离体回肠平滑肌收缩的影响,探讨其作用机理.方法:采用在体方法观察连钱草乙醇提取物对小鼠小肠推进功能的影响,采用离体方法观察连钱草乙醇提取物对豚鼠回肠平滑肌运动功能的影响.结果:连钱草乙醇提取物能够显著抑制小鼠小肠炭末推进率(P＜0.01),缓解大黄所致小鼠腹泻 (P＜0.01),对抗新斯的明所致的肠蠕动亢进 (P＜0.01).抑制豚鼠离体回肠平滑肌收缩(P＜0.01),拮抗乙酰胆碱、组胺、氯化钡对离体豚鼠回肠平滑肌的激动作用(P＜0.01).结论:连钱草乙醇提取物具有抑制肠蠕动作用,这种作用可能由胃肠道的胆碱能受体和组胺受体介导,或直接作用于回肠平滑肌细胞.     

川芎嗪注射液对离体豚鼠气管平滑肌作用机制探讨

目的 :研究川芎嗪对离体豚鼠气管平滑肌的作用及机制。方法 :取豚鼠气管制成气管片 ,用体外实验方法分别记录川芎嗪对豚鼠气管平滑肌的作用以及在钙通道和不同受体阻断剂孵育的条件下对豚鼠气管平滑肌的作用的变化。结果 :川芎嗪对离体豚鼠气管平滑肌有明显的舒张作用 (P <0 .0 1) ,呈剂量依赖性 (10 -5.5～ 10 -3 mol·L-1) ,其作用可以被普萘洛尔 (心得安 )所拮抗 ;其与硝苯地平有协同舒张气管平滑肌的作用 ;M受体阻滞剂阿托品对川芎嗪的作用无明显影响。结论 :川芎嗪对离体豚鼠气管平滑肌有明显的舒张作用 ,其机制很可能是通过作用于气管平滑肌上的 β2 受体 ,抑制细胞外Ca2 的内流而导致气管平滑肌的舒张。     

双喘通药理作用的研究

本文比较了双喘通与喘通的平喘作用。二者弛张豚鼠离体气管平滑肌作用和对抗组织胺收缩豚鼠离体气管平滑肌作用,在低浓度时相近,在较高浓度时双喘通强于喘通。延长组织胺气雾对豚鼠致喘时间的作用,喘通强于双喘通。心得安不能阻断双喘通对离体气管和离体子宫平滑肌的弛张作用,但能阻断喘通的作用。双喘通可拮抗 Ach 和 BaCl_2对离体气管和离体肠管平滑肌的收缩作用。双喘通对豚鼠离体回肠具有弛张作用和解痉作用。双喘通给小鼠静脉注射 LD_(50)为10.0±0.2mg/kg,灌胃给药 LD_(50)为64.0±8.6mg/kg。     

庆大霉素对组胺所致豚鼠离体肠肌收缩的拮抗作用

目的观察庆大霉素对组胺所致豚鼠离体回肠的拮抗作用。方法离体豚鼠回肠经庆大霉素预处理后加入不同浓度组胺,记录肠肌收缩的幅度。结果发现庆大霉素能部分对抗组胺诱发的肠肌收缩,对组胺的减活指数为4.45,甚至对肠肌也有直接的舒张作用。结论庆大霉素对肠肌具有舒张作用,此作用在庆大霉素口服治疗感染性胃肠炎方面具有减轻症状的意义。     

盐酸戊乙奎醚对豚鼠离体回肠/结肠的解痉作用

目的　研究盐酸戊乙奎醚 (PHC)对豚鼠离体回肠 /结肠肌条的抑制收缩作用。方法　将豚鼠离体回肠 /结肠条悬吊于麦氏浴槽中 ,测量给药PHC后豚鼠离体肌条自主收缩及乙酰胆碱 (Ach)所致痉挛收缩的最大张力 ,计算抑制 5.0 %收缩的PHC的浓度。结果　PHC对豚鼠离体回肠 /结肠肌条的自主收缩有明显抑制作用 ,对乙酰胆碱 (Ach)所致的痉挛性收缩有明显的松弛作用。结论　PHC能有效地缓解离体回肠 /结肠的痉挛状态。     

3种生物来源的PLA2对豚鼠回肠M受体的激动作用

目的了解蛇毒MP成分对M受体的激动作用是否为PLA2的共性。方法采用离体生物测定法,分别测定蛇毒MP成分、蜂毒PLA2和猪胰腺PLA2等3种PLA2对豚鼠回肠纵行肌标本张力的影响,绘制量效曲线,计算EC50值。观察阿托品对3种PLA2对豚鼠回肠作用的影响。结果3种PLA2均能剂量依赖性地引起离体豚鼠回肠纵行肌的收缩效应,但最大作用强度仅为CCh的40％～50％。蛇毒PLA2和蜂毒PLA2的EC50值分别为29．5nmol·L-1和24．1nmol·L-1,与CCh的EC50值相当。阿托品能部分拮抗PLA2对豚鼠回肠的收缩作用。结论3种PLA2均具有激动M受体的作用。     

蜂斗菜不同提取物对豚鼠离体回肠收缩的影响

目的 比较蜂斗菜不同提取物对豚鼠离体回肠收缩的影响。方法 采用豚鼠离体回肠实验,以组胺、乙酰胆碱不同激动剂为研究模型,比较蜂斗菜CO₂超临界提取物、80%乙醇提取物、80%乙醇提取物的不同极性提取物及乙酸乙酯提取物经硅胶柱层析分离获得的不同馏分对豚鼠离体回肠的收缩作用,计算各个提取物对豚鼠回肠收缩幅度的抑制率。结果 蜂斗菜不同提取物对组胺、乙酰胆碱所致的豚鼠离体回肠收缩有显著拮抗作用,其中乙酸乙酯提取物硅胶柱色谱的馏分抑制作用最强。结论 蜂斗菜不同提取物均能抑制组胺、乙酰胆碱引起的豚鼠离体回肠收缩作用,脂溶性成分抑制作用最强,其机制可能与M、H₁受体的抑制有关。     

General pharmacological profile of the novel muscarinic receptor agonist SNI-2011, a drug for xerostomia in Sjögren's syndrome. 2nd communication: effects on somatic nervous system and on autonomic nervous system and smooth muscle

A novel muscarinic receptor agonist SNI-2011 ((+/-)-cis-2-methylspirol[1,3-oxathiolane-5,3'-quinuclidine] monohydrochloride hemihydrate, cevimeline, CAS 153504-70-2), is a candidate therapeutic drug for xerostomia in Sj?gren's syndrome. The general pharmacological properties of this drug on the somatic nervous system and on the autonomic nervous system and smooth muscle were investigated in mice, rats, guinea pigs, rabbits and cats. 1. Somatic nervous system: SNI-2011 had no effect on the neuromuscular junction in rats and no muscle relaxant effect in mice. No surface anesthetic effect was observed in guinea pigs, but infiltration anesthetic effect was found after intracutaneous injection of solution (1% or higher). 2. Autonomic nervous system and smooth muscle: SNI-2011 tended to cause mydriasis at 3 mg/kg i.v. or higher in rabbits and dose-dependently caused mydriasis at 10 mg/kg p.o. or higher in rats. Mydriasis in rats was also observed by ophthalmic instillation, caused via the peripheral muscarinic acetylcholine receptors. SNI-2011 elevated the base line tension of nictitating membrane in cats when it was injected intravenously at 3 mg/kg or higher. In the smooth muscle, SNI-2011 increased the spontaneous movement of isolated rabbit ileum (1 x 10(-6) mol/l or higher), contractions of isolated guinea pig ileum (1 x 10(-6) mol/l or higher) and isolated guinea pig trachea (3 x 10(-6) mol/l or higher). SNI-2011 relaxed the histamine- and noradrenaline-induced contractions of isolated guinea pig aorta and augmented noradrenaline- and phenylephrine-induced contractions of isolated rat vas deferens. These effects were induced by relatively higher concentrations only i.e. 1 x 10(-5) mol/l or higher. From these results, SNI-2011 has muscarinic side effects on the somatic nervous system and on the autonomic nervous system and smooth muscle, however, in the case of oral administration, that is clinical administration route, SNI-2011 caused no muscarinic side effect at the effective doses needed for saliva secretion.     

Characterization of the effect of penehyclidine hydrochloride on muscarinic receptor subtypes mediating the contraction of guinea‐pig isolated gastrointestinal smooth muscle

Objectives The aim was to characterize the effect of penehyclidine hydrochloride, which mediates the relaxation of guinea‐pig isolated gastrointestinal smooth muscle, on muscarinic receptor subtypes. Methods Radioimmune assay was used to determine cAMP levels in isolated guinea‐pig gastrointestinal smooth muscle to compare the selective effects of penehyclidine hydrochloride on muscarinic receptor subtypes. Key findings The results indicated that the relaxing effect of penehyclidine hydro‐chloride on isolated gastrointestinal smooth muscle contraction induced by acetylcholine was stronger than that of atropine (based on PA₂ values). In the radioimmune assay, penehyclidine hydrochloride increased the cAMP content in isolated guinea‐pig stomach smooth muscle and decreased the cAMP content in isolated guinea‐pig intestinal smooth muscle, but the difference was not statistically significant at a dose of 10 μmol/1. Conclusions The results suggest that penehyclidine hydrochloride has little or no effect on M₂ receptor subtypes in guinea‐pig gastrointestinal smooth muscle.     

瘤果黑种草子挥发油平喘作用的研究

目的研究瘤果黑种草子挥发油平喘作用及其机制。方法采用整体动物喷雾致喘实验观察瘤果黑种草子挥发油的平喘作用;通过豚鼠肺支气管灌流法及离体回肠实验考察对气道平滑肌的舒张作用。结果低、高剂量(0.1和0.4mL·kg-1)瘤果黑种草子挥发油可明显延长小鼠哮喘反应的潜伏期,与对照组比较,差异具有统计学意义(P<0.01);低、中、高剂量(3,6和12μL·mL-1)挥发油明显增加豚鼠肺灌流量,降低豚鼠回肠平滑肌收缩张力,与对照组比较,差异具有统计学意义(P<0.01)。结论瘤果黑种草子挥发油具有一定的平喘作用,其作用机制可能与激动β2受体、拮抗M受体有关。     

葛缕酮的气道扩张作用和呼吸道抗过敏作用

目的观察留兰香油中葛缕酮的气道扩张作用和对呼吸道介质的影响。方法用豚鼠药物引喘法、豚鼠离体气管片法、致敏豚鼠肺组织ＳＲＳ Ａ释放和拮抗ＳＲＳ Ａ、致敏豚鼠离体气管Ｓｃｈｕｌｔｚ Ｄａｌｅ反应法检测。结果葛缕酮对豚鼠药物性哮喘具有保护作用,灌胃给药延长５０％剂量为７６ｍｇ·ｋｇ－１,气雾给药为６３ｇ·Ｌ－１;对豚鼠离体气管有直接松弛作用,ｐＤ２值为４２７±００８,并有抗氨甲酰胆碱作用;能抑制致敏豚鼠肺组织ＳＲＳ Ａ的释放,ＩＣ５０为１８ｍｇ·Ｌ－１,拮抗ＳＲＳ Ａ收缩回肠的ＩＣ５０为２７ｍｇ·Ｌ－１,并能抑制致敏豚鼠离体气管的Ｓｃｈｕｌｔｚ Ｄａｌｅ反应。结论葛缕酮具有气道扩张作用和呼吸道抗过敏作用。     

新平喘药—α-萜品烯醇的药理作用

艾叶油平喘成分α-萜品烯醇在豚鼠整体和离体实验中具有气道松弛作用,能升高气管平滑肌内cAMP含量,还有抗过敏、镇咳和祛痰作用,并且毒性低,为一安全有效的新平喘药。本品不同于β受体激动剂,对豚鼠离体心房具有抑制作用。     

Effects of CP-96,345, a novel non-peptide antagonist of NK1 receptor, on the peristalsis in isolated guinea pig ileum.

CP-96,345, a novel non-peptide antagonist of the NK1 receptor, at 10(-8)-10(-6) M decreased the frequency of peristalsis and reduced peristalsis-associated longitudinal muscle contractions in isolated guinea pig ileum. In the presence of 10(-6) M CP-96,345, further addition of 10(-6) M atropine blocked the peristalsis. When 10(-6) M atropine was first applied, more than half of the preparations developed atropine-resistant peristalsis. CP-96,345 at 10(-6) M blocked the atropine-resistant peristalsis. These results are consistent with the view that substance P is involved in the peristalsis in guinea pig ileum.     

Comparison of the relaxing effects of cicletanine and cromakalim on vascular smooth muscle.

Cicletanine inhibited the spontaneous activity of portal vein preparations (rat, guinea pig, and rabbit) and that produced by norepinephrine or an increase in external K+ concentration to 20 mmol/L in seven types of vascular smooth muscle preparation (portal vein of rat, guinea pig, and rabbit; aorta of rat and guinea pig; and iliac artery and ear artery of rabbit). The cicletanine EC50 was approximately 10(-4) mol/L. Contractions produced by K+ = 80 mmol/L were also inhibited by cicletanine in most preparations. Only in aortic strips of rat and guinea pig and in rabbit iliac artery were the concentration-response relationships for cicletanine shifted to the right, yielding EC50 values of approximately 3 x 10(-4) mol/L. In contrast, the inhibitory effects of the potassium channel opener cromakalim (BRL 34915) were completely abolished during K+ = 80 mmol/L treatment in all preparations. The inhibitory effect of cromakalim under the other test conditions (above) was completely antagonized by application of glibenclamide, 10(-5) mol/L, whereas this treatment had only negligible effects on cicletanine inhibition in most preparations. The results indicate that a potassium channel opening effect does not contribute significantly to the inhibitory effect of cicletanine on vascular smooth muscle.     

人重组白细胞介素-1受体拮抗剂对豚鼠离体气管平滑肌的影响

目的观察人重组白细胞介素-1受体拮抗剂（IL-1ra）对豚鼠离体气管平滑肌（TSM）的影响。方法用离体器官装置、张力换能器、MedLab记录系统测定TSM张力。结果IL-1ra对正常TSM和卵白蛋白致敏TSM有直接舒张作用，EC₅₀分别为8.06×10^-8和5.88×10^-7mol·L^-1。IL-1ra可剂量依赖性抑制或拮抗His，ACh和5-HT引起的气管收缩。但低浓度却增强ACh收缩作用。IL-1ra亦能显著抑制或对抗卵白蛋白致敏豚鼠的气管收缩，IC₅₀为4.48×10^-7 mol·L^-1。结论在一定浓度范围内，IL-1ra对正常、痉挛和致敏的豚鼠离体气管平滑肌都有松弛作用。