鸭嘴花碱对豚鼠离体气管平滑肌收缩功能的影响

目的：研究鸭嘴花碱对组胺和乙酰胆碱所致气管收缩的抑制作用。方法：离体豚鼠气管条。结果：鸭嘴花碱能抑制氯化钾、乙酰胆碱、磷酸组胺所致气管平滑肌收缩，而且能使磷酸组胺、乙酰胆碱收缩气管平滑肌的量效曲线右移，并抑制最大效应，其作用为剂量依赖性。结论：鸭嘴花碱对气管平滑肌具有显著舒张作用。     

DDPH对多种介质所致豚鼠离体气管平滑肌收缩的影响

目的：研究ＤＤＰＨ对多种介质引起的豚鼠离体气管平滑肌收缩的影响。方法：离体器官平滑肌实验法。结果：不同剂量的ＤＤＰＨ可非竞争性抑制Ｈｉｓｔ，ＡＣｈ及Ｃａ＾２＋的作用，使它们的量效曲线非平行右移，最大反应变低，其ｐＤ’２值分别为４．０９，３．９５，３．９５。ＤＤＰＨ还抑制Ｋ＾＋所致气管平滑肌收缩，但作用较维拉帕米弱，它们的ＩＣ５０值分别为１１．７５和１．５８μｍｏｌ／Ｌ。结论：ＤＤＰＨ通过非竞争性Ｃ     

骆驼蓬生物碱乳膏剂的质量标准研究

摘 要 目的： 初步建立骆驼蓬生物碱乳膏剂的质量控制方法。方法: 按照《中国药典》2010年版一部附录有关制剂通则要求,对制剂进行一般质量检查。以去氢骆驼蓬碱和骆驼蓬碱为指标,采用薄层色谱法对乳膏剂进行薄层色谱鉴别。以去氢骆驼蓬碱、骆驼蓬碱、鸭嘴花碱为指标,采用高效液相色谱法对制剂进行含量测定。结果: 检查项目均符合《中国药典》要求。薄层色谱中供试品在与对照品相同位置上显相同颜色斑点。去氢骆驼蓬碱、骆驼蓬碱和鸭嘴花碱分别在3.440～110.000 μg·ml^-1、3.340～107.000 μg·ml^-1和1.380～22.000 μg·ml^-1浓度范围内线性关系良好,平均回收率分别为98.1% (RSD=1.75%, n=6)、99.8% (RSD=1.78%,n=6)和99.3% (RSD=1.95%,n=6)。结论:所建立的质量控制方法符合方法学要求,为最终制定骆驼蓬生物碱乳膏剂质量标准奠定了试验基础。     

雌二醇对离体和在体气管平滑肌收缩活动的抑制作用

目的:研究雌二醇对离体和在体气管平滑肌收缩的作用.方法:(1)将家兔离体气管平滑肌条置于装有Krebs液的肌槽中温育,并通入95％O_2和5％CO_2的混合气体.二导记录仪记录肌条的等长张力.(2)测量肌注雌二醇(1mg/kg)前后乙酰胆碱和组胺引发豚鼠哮喘的潜伏期.结果:(1)雌二醇(100μmol/L)对乙酰胆碱和氯化钾诱发的收缩有明显的舒张作用(舒张百分比分别为39％±5％和45％±19％).其作用可被蚓哚美辛和亚甲蓝部分阻断(26％±8％和28％±13％),但不能被L-NNA、心得安和去除上皮所影响(舒张百分比分别为38％±10％,40％±15％,37％±8％).雌二醇能使乙酰胆碱及氯化钙的量效曲线明显右移(pD_2~′值分别为3.98和4.75).另外,雌二醇可明显抑制乙酰胆碱引起的第Ⅰ时相性收缩,对氯化钙引起的第Ⅱ时相性的收缩无明显影响.(2)肌注雌二醇(1mg/kg)可使豚鼠的引喘潜伏期明显延长.结论:(1)雌二醇对兔离体气管平滑肌的作用是非上皮依赖性的,与抑制电压依赖性钙通道和细胞内钙从内质网的释放有关,还部分与cGMP介导的松弛途径及刺激气道平滑肌释放前列腺素类物质有关,但与β-肾上腺素能受体介导的舒张无关.(2)雌二醇可明显舒张豚鼠在体气管平滑肌.     

神香草不同洗脱物对豚鼠离体气管平滑肌收缩的影响

目的:考察维药神香草不同洗脱物对豚鼠离体支气管平滑肌收缩的影响。方法:制备豚鼠离体气管环后浸泡于克-亨液中,以乙酰胆碱(ACh,1×10~(-7)g/mL)或组胺(His,1×10~(-6)g/mL)致气管环收缩,然后分别考察质量浓度为0.08、0.16、0.32、0.64、1.28、2.56 mg/mL的神香草水洗脱物和30%、50%、60%、70%、95%的乙醇洗脱物对气管环收缩的影响,记录收缩曲线并计算解痉率;试验均以生理盐水为空白对照,以氨茶碱(0.08 mg/mL)为阳性对照。结果:与空白对照比较,0.16~2.56 mg/mL的30%、50%乙醇洗脱物,0.32~2.56 mg/mL的60%乙醇洗脱物以及0.64~2.56 mg/mL的70%、95%乙醇洗脱物均可明显抑制ACh致气管环收缩,解痉率均明显升高(P<0.05或P<0.01);0.32~2.56 mg/mL的水洗脱物和30%、50%乙醇洗脱物,0.16~2.56 mg/mL的60%、70%乙醇洗脱物以及1.28~2.56 mg/mL的95%乙醇洗脱物可明显抑制His致气管环收缩,解痉率均明显升高(P<0.05或P<0.01);其中2.56 mg/mL的60%乙醇洗脱物作用效果与氨茶碱接近。结论:神香草不同洗脱物对ACh或His致豚鼠离体支气管平滑肌收缩均有一定的抑制作用;其中以60%乙醇洗脱物作用最强,其在高质量浓度下作用与氨茶碱相当。     

去上皮对离体气管平滑肌反应性的影响

去上皮致敏豚鼠气管标本对乙酰胆碱，组胺，Ｐ物质和氯化钡的敏感性比未去上皮本为高。上述药物在去上皮标本上得到ＥＣ５０仅为未去上皮的１／６－１／３０。由抗原抗体反应或电场刺激所引起的去上皮标本的收缩幅度和对照组相比升高了５０％－１００％，主些实验结果提示，气管上皮对呼吸道，尤其是对其过敏性收缩具有重要调节作用。     

骆驼蓬总生物碱提取物的质量标准研究

以骆驼蓬碱和去氢骆驼蓬碱为指标,采用薄层色谱和高效液相色谱等方法对骆驼蓬总生物碱提取物进行定性和定量质量控制.薄层色谱中供试品在与对照品相同位置上显相同颜色斑点,其它各项检测结果(如水分、灰分、浸出物、重金属检查)均符合中国药典要求.骆驼蓬碱和去氢骆驼蓬碱分别在2～200和0.8～320μg/ml浓度范围内线性关系良好,平均回收率为99.7%(RSD=1.89%)和100.7%(RSD=1.78%),日内及日间RSD小于2%.     

地塞米松对豚鼠离体气管平滑肌收缩功能的影响

在体外研究了地塞米松（Ｄｅｘ）对豚鼠离体气管平滑肌收缩的影响。ＣａＣｌ２和组胺（Ｈｉｓ）引起了气管条明显的收缩，ｐＤ２分别为３．９及５．９２。用地塞米松温育后，氯化钙和组胺的量效曲线均明显降低，ｐＤ＇２分别为４．７４和６．６７。Ｄｅｘ对Ａｃｈ３×１０－６ｍｍｏｌ·Ｌ－１和前列腺素Ｆ２α３ｍｍｏｌ·Ｌ－１引起的支气管平滑肌收缩也有逆转作用，ＩＣ５０分别为２．４１×１０－５ｍｏｌ·Ｌ－１和４．２６×１０－４ｍｏｌ·Ｌ－１，提示Ｄｅｘ有明显的支气管扩张作用。     

The influence of post-mortem conditions on contractile and relaxant responsiveness of guinea-pig isolated tracheal smooth muscle

Responsiveness to various contractile and relaxant agonists was assessed in tracheal preparations from guinea-pigs that had been incubated in situ at 4–37°C for 0–168h post-mortem. The potencies of histamine and acetylcholine were increased up to 168h at 4°C post-mortem and up to 24h post-mortem at 22°C. Histamine potency also increased with increasing post-mortem time at 37°C. After 48h at 22°C and 8h at 37°C, responses to all spasmogens were abolished. Increases in histamine and acetylcholine potencies were similarly observed in tracheal tissue that had been removed at death and then incubated at 4°C in oxygenated Krebs-bicarbonate solution for 0–168h. The increased potency of these drugs may be explained by epithelial damage and/or loss of an epithelium-derived inhibitory factor (EpDIF). Both basal and spasmogen-stimulated increases in intracellular phosphoinositides fell with increasing time and ambient temperature post-mortem, despite the fact that contraction in response to these agonists could still be evoked. This suggests the selective failure of this signal transduction pathway and the maintenance of responsiveness via other mechanisms. The potencies and maximum effects of relaxant agonists remained unaltered in tracheal tissue with increasing time post-mortem, suggesting little change in the function of the appropriate receptor-signal transduction processes. This study has therefore demonstrated that at 4°C, contractile and relaxant responses were preserved for up to 168h post-mortem, although the modulatory influence of the epithelium on histamine and acetylcholine responses was rapidly lost. Received: 5 August 1997 / Accepted: 8 December 1997     

The effect of histamine on cyclic AMP levels in guinea-pig tracheal smooth muscle

Histamine (10(-5)--3 x 10(-4) M) increased the cylic AMP content of guinea-pig tracheal smooth muscle, the maximal effect being a 3-fold increase after 2-min incubation with 10(-4) histamine. Histamine-induced accumulation of cyclic AMP was not affected by propranolol or atropine, but was reduced by mepyramine. Aspirin and indomethacin abolished the cyclic AMP response to histamine and potentiated histamine-induced contractions of the smooth muscle. These results suggest that the elevation of cyclic AMP levels in response to histamine is mediated by prostaglandins, and represents an important negative feedback regulatory mechanism which modulates the contractile response of guinea-pig tracheal smooth muscle to histamine.     

Mechanism of soman-induced contractions in canine tracheal smooth muscle

The actions of the irreversible organophosphorus cholinesterase (ChE) inhibitor soman were investigated on canine tracheal smooth muscle in vitro. Concentrations of soman 1 nM increased the amplitude and decay of contractions elicited by electric field stimulation. The effect on decay showed a marked dependence on stimulation frequency, undergoing a 2.4-fold increase between 3 and 60 Hz. Soman also potentiated tensions due to bath applied acetylcholine (ACh). Little or no potentiation was observed for contractions elicited by carbamylcholine, an agonist that is not hydrolyzed by ChE. Concentration of soman 3 nM led to the appearance of sustained contractures. These contractures developed with a delayed onset and were well correlated with ChE activity. Alkylation of muscarinic receptors by propylbenzilylcholine mustard antagonized the actions of soman on both spontaneous and electrically-evoked muscle contractions. The results are consistent with a mechanism in which the toxic actions of soman are mediated by accumulation of neurally-released ACh secondary to inhibition of ChE activity. An important factor in this accumulation is suggested to be the buffering effect of the muscarinic receptors on the efflux of ACh from the neuroeffector junction.The opinions or assertions contained herein are the private views of the authors and are not to be construed as official views of the Army or the Department of Defense. In conducting the research described in this report, the investigators adhered to the Guide for the Care and Use of Laboratory Animals as adopted and promulgated by the National Institutes of Health     

Characteristics of histamine tachyphylaxis in canine tracheal smooth muscle

Summary In isolated canine tracheal smooth muscle, repeated administrations of histamine result in a rapid reduction in contractile response to about 15% of the initial contraction (tachyphylaxis). Development of this tachyphylaxis is specific inasmuch as: 1) it does not develop to acetylcholine (10^–6 M or 10^–4 M), or serotonin (10^–5 M); and 2) maximally developed histamine tachyphylaxis is not associated with a parallel reduction in response to acetylcholine. Pretreatment with propranolol (10^–5 M) or phentolamine (10^–4 M) does not prevent tachyphylaxis: however, pretreatment with atropine (10^–4 M) does prevent tachyphylaxis in about 50% of the animals tested.Tachyphylaxis to histamine can be reversed in a dose- and time-dependent fashion with prostaglandin synthesis inhibiting agents. The order of potency obtained with such compounds (indomethacin > mefenamic acid > oxyphenbutazone > acetylsalicylic acid) is consistent with potencies for inhibition of prostaglandin synthesis found in the literature. Also, in indomethacin pretreated strips in which tachyphylaxis to histamine was prevented, exogenous addition of PGE₂ (1.42×10^–10 M to 2.84×10^–9 M) and PGA₂ in a high concentration (2.9×10^–9 M) are capable of selectively reducing the response to histamine without an effect on acetylcholine-induced contractions. These data suggest that the mechanism of histamine tachyphylaxis in the canine tracheal smooth muscle preparation involves prostaglandin synthesis.This report is part of a dissertation to be presented by W. H. A. to the University of South Florida College of Medicine in partial fulfillment of the requirements for a Doctor of Philosophy degree     

Competitive inhibition of sodium-dependent high affinity choline uptake by harmala alkaloids

The actions of five harmala alkaloids on the sodium dependent high affinity choline uptake activity in rat striatal synaptosomes was investigated. All five compounds were found to be competitive inhibitors of the uptake system. Harmalol (K_i ～ 3.4 μM) and 2-methylharmine (K_i ～ 5.7 μM) were found to be relatively potent inhibitors in a series with an ascending order of inhibitory potency of harmaline<2-methylharmaline<harmine<2-methylharmine<harmalol.     

The influence of neuraminidase treatment on tracheal smooth muscle contraction

To examine the role of sialic acid in the respiratory tract, the influence of neuraminidase from Clostridium perfringens was investigated on contractions of isolated guinea-pig and rat trachea and on histamine release from guinea-pig lung tissue. Treatment with 2.0 units/ml of neuraminidase at 37°C and pH 7.4 for 30 min caused an approximately 60% removal of total N-acetylneuraminic acid, a representative sialic acid, from muscle from guinea-pig and rat trachea. Neuraminidase concentration dependently induced histamine release from guinea-pig chopped lung tissue, but has no effect on contractions produced by acetylcholine, histamine and 5-hydroxytryptamine. Pretreatment with 2.0 units/ml of neuraminidase inhibited the contraction induced by antigen (ovalbumin) or compound 48/80. These findings suggest, at least in part, that sialic acids sensitive to neuraminidase are involved in the regulation of histamine release but not tracheal contraction.     

重组人白细胞介素-1受体拮抗药对豚鼠离体呼吸道平滑肌的影响

目的　观察人重组白细胞介素 1受体拮抗剂 (IL 1ra)对正常和卵白蛋白致敏豚鼠离体肺条、气管平滑肌的影响。方法　应用离体器官装置、张力换能器、MedLab记录系统测定肺条和气管平滑肌的张力。结果　①IL 1ra对正常豚鼠离体肺条和气管平滑肌有直接松弛作用 ,EC50 分别为1 2 9ⅹ 10 -7mol·L-1和 8 0 6× 10 -8mol·L-1;并对卵白蛋白致敏的豚鼠肺条和气管平滑肌也有直接的松弛作用 ,EC50 分别为 2 6 1× 10 -7mol·L-1和 5 88× 10 -7mol·L-1,但致敏豚鼠呼吸道平滑肌对IL 1ra的敏感性要比正常豚鼠低。②IL 1ra(10 -9～ 10 -5mol·L-1)可剂量依赖性地抑制致痉剂组胺对正常豚鼠肺条和气管平滑肌的收缩作用 (P <0 0 1)。③IL 1ra能抑制卵白蛋白攻击引起的肺条和气管平滑肌的收缩 ,IC50 分别为 7 83ⅹ 10 -7mol·L-1和 4 4 8ⅹ 10 -7mol·L-1。结论　IL 1ra对正常、痉挛及致敏状态的呼吸道平滑肌均有松弛作用     

Effects of Artesunate on Tracheal Smooth Muscle from the Guinea—pig

Artesunae is a derivative of qinghaosu,with a sesquiterpene structure.The specific action and the clinical uses of artesunate are on the preliminary stage,on the one hand ,artesunate has specific action of both antiinflammation and antivirus,and also has protective effect on the pulmonary alveolar macrophages,whuich may be advantageous to the treatment of the airway non-specific inflammation of asthma,.On the other hand,qinghaousu has the activities to relax vascular smooth muscle and to cause hypotension.The expectorant action,the antitussive action and the antuiasthmatic action of qinghaosu were preported.Artesunate may also have antiasthmatic activity,because the antimalarial potency of artesunate is stronger than that of qinghaosu,and Artesunate can block Ca^2 influx by inhibiting calcium-dependent chloride current.The main aims of this paper are to investigate the site,the mode,and the mechanism of artesunate action on isolated tracheal smooth muscle from the guinea-pig.