鱼腥草油抗慢反应物质及平喘作用的研究

鱼腥草油能明显拮抗SRS-A对豚鼠离体回肠和肺条的作用,静脉注射100mg/kg能拮抗SRS-A增加豚鼠肺溢流的作用;并能明显抑制致敏豚鼠离体回肠的过敏性收缩,及拮抗HA、Ach对豚鼠回肠的收缩;对豚鼠过敏性哮喘具有明显的保护作用。     

豚鼠肺膜LTD4受体结合特征及二苯乙烯低聚体(Gn-3)的LTD4受体拮抗作用

 目的 采用LTD₄放射受体结合实验方法,在分析LTD₄受体的有关特征的基础上,观察比较二苯乙烯低聚体(Gn-3)对LTD₄受体的拮抗作用。方法 以豚鼠肺膜为实验材料,采用³H-LTD₄为放射配体,以FPL₅₅₇₁₂作阳性对照药物,Gn-3为实验药物,进行药物竞争结合实验。采用离体器官生物检测法鉴定Gn-3对LTD₄受体的拮抗作用。结果³H-LTD₄与其相应受体呈现单一结合位点,其Kd和B_max值分别为19.9×10^-11mol·L^-1和232.9 fmol·mg^-1蛋白。Gn-3可明显取代³H-LTD₄与其受体结合,IC₅₀值为5.71×10^-7 mol·L^-1,Ki值为2.54×10^-7 mol·L^-1。生物学鉴定法证实Gn-3可抑制LTD-4引起的生物学效应。结论 豚鼠肺膜LTD₄受体为单一结合位点受体,Gn-3为高活性的LTD4受体拮抗剂。     

补骨脂素的植物雌激素作用及其机制探讨

目的:利用雌激素受体(ER)α,β阳性T47D细胞和子宫内膜癌Ishikawa细胞观察补骨脂素的雌激素样作用,并探讨其可能的作用机制。方法:以1×10^-8mol.L^-1雌二醇(E₂)为阳性对照药,利用MTT细胞增殖试验观察1×10^-5~1×10^-9mol.L^-1补骨脂素对T47D增殖的影响,同时观察1×10^-6mol.L^-1和1×10^-7mol.L^-1补骨脂素对Ishikawa细胞增殖的影响;以半定量RT-PCR法检测1×10^-6mol.L^-1和1×10^-7mol.L^-1补骨脂素对T47D细胞雌激素效应基因PR mRNA表达情况的影响;并以雌激素受体拮抗剂ICI 182,780为工具药进行干预。同时,通过流式细胞术检测1×10^-6mol.L^-1和1×10^-7mol.L^-1补骨脂素引起T47D细胞ER-α,ER-β含量的变化。结果:1×10^-5~1×10^-7mol.L^-1补骨脂素能够显著促进T47D细胞增殖;1×10^-6mol.L^-1和1×10^-7mol.L^-1补骨脂素对Ishikawa细胞增殖也有显著的促进作用;RT-PCR结果显示:1×10^-6mol.L^-1和1×10^-7mol.L^-1补骨脂素可使T47D细胞PR mRNA表达显著增加,表现出雌激素样作用,而且以上效应可被ICI 182,780拮抗。1×10^-6mol.L^-1和1×10^-7mol.L^-1补骨脂素还可诱导T47D细胞ER-α,ER-β表达明显增加。结论:补骨脂素具有植物雌激素作用,并且其作用是通过ER途径介导的。     

橐吾中倍半萜对二氢吡啶类受体的作用研究

 目的：观察8个倍半萜类化合物对二氢吡啶类受体结合的作用和对离体血管张力的影响。方法：用［3H］尼群地平对猪心室肌微粒体膜受体结合方法和家兔离体血管条实验对化合物的体外作用进行研究。结果：化合物Ⅰ、Ⅱ、Ⅲ对尼群地平与受体结合有明显抑制作用，其IC₅₀分别为2.0×10^-5mol·L^-1，2.7×10^-5mol·L^-1和3.9×10^-5mol·L^-1，其余化合物作用较弱。这些化合物抑制受体结合的作用强度与结构中母核与取代基的改变有关，而取代基的变化对活性的影响更重要。化合物Ⅱ、Ⅲ对高K+引起的兔胸主动脉收缩有剂量依赖性的抑制作用。结论：这类化合物有钙拮抗作用，作用机制可能与影响二氢吡啶类受体有关；它们作用有量效关系和构效关系，提示有以此为先导进行深入结构改造和构效关系研究的价值。     

野罂粟总碱抗过敏实验研究

目的:研究野罂粟总碱(Papavernudicauletotalalkaloid,PNTA)的抗过敏作用。方法:豚鼠致敏5周后断颈处死,取出肺组织切碎后37℃恒温孵育,制备肺组织过敏介质(SRS-A),观察不同浓度的PNTA对SRS-A、卵蛋白引起豚鼠回肠的收缩幅度的影响。结果:10,20,40μg·ml-1PNTA对卵蛋白引起致敏回肠的收缩反应有明显的抑制作用,对肺液引起的豚鼠回肠收缩有明显的拮抗作用。结论:PNTA对SRS-A及卵蛋白引起的过敏反应有显著的拮抗作用。     

苦丁茶对豚鼠离体气管平滑肌收缩功能的影响

目的 :研究苦丁茶对豚鼠离体气管平滑肌的影响。方法 :以累积技术建立CaCl₂ 和组织胺 (His)的量效曲线 ,研究了苦丁茶对CaCl₂ ,His和乙酰胆碱 (Ach)等致喘介质对豚鼠离体气管平滑肌收缩功能的影响。结果 :CaCl₂ 和His引起气管条明显的收缩 ,pD₂ 分别为 3.59和 5 .34。苦丁茶能明显压低CaCl₂ 和His的量效曲线 ,并使曲线右移。苦丁茶对Ach和His 3×10^-6mmol·L^-1引起的气管平滑肌收缩有明显的逆转作用 ,IC₅₀ 分别为 0.16mg·ml^-1和 0.2 1mg·ml^-1。结论 :提示苦丁茶有明显的舒张豚鼠离体气管平滑肌的作用。     

问荆碱对大鼠脑囊泡膜Mg2+-ATPase,Ca2+-ATPase抑制作用的动力学研究

问荆碱对大鼠脑囊泡膜Mg²⁺-ATPase,Ca²⁺-ATPase有显著的抑制作用,对Mg²⁺-ATPase的抑制机制分别为竞争性抑制(Mg²⁺,Ki=4.93×10^-5mol/L)、非竞争性抑制(ATP,Ki=1.06×10^-4mol/L),对Ca²⁺-ATPase的抑制机制分别为混合型抑制(Ca²⁺,Ki=5.07×10^-5mol/L)、非竞争性抑制(ATP,Ki=3.27×10-4mol/L)。     

缬沙坦对巨噬细胞凝集素样氧化低密度脂蛋白受体表达的影响

 目的　研究Ang II I型受体(AT₁)拮抗剂缬沙坦(valsartan)对巨噬细胞(THP-1细胞 )血凝素样氧化低密度脂蛋白受体(LOX-1)基因转录和蛋白表达的影响,以探讨valsartan在抗动脉粥样硬化(AS)中的地位和作用。方法　分别用不同浓度的val sartan预作用已诱导分化的THP-1细胞0.5h后,再加入Ang II(1.0×10^-6mol·L^-1)24h后,用细胞酶联免疫法和半定量RT-PCR分别检测LOX-1蛋白和mRNA表达的情况。结果　1.0×10^-5mol·L^-1的valsartan可完全拮抗Ang II诱导的THP-1细胞LOX-1蛋白和LOX-1 mRNA表达作用,1.0×10^-6,1.0×10^-7,1.0×10^-8和1.0×10^-9mol·L^-1的valsartan分别可降低Ang II诱导的LOX-1蛋白表达作用达100%,85.8%,47.2%和9.8%;降低AngII诱导的LOX-1 mRNA表达作用达95.1%,82.6%,63.0%和20.0%。结论　valsartan可浓度依赖地显著拮抗AngII诱导THP-1细胞LOX-1蛋白和mRNA的表达,从而可能减少巨噬细胞通过LOX-1途径的OX-LDL摄入,影响泡沫细胞的形成、AS的发展,发挥其抗AS作用。     

氟哌啶醇对猪冠状动脉螺旋肌条作用的研究

 目的：观察氟哌啶醇(Hal)拮抗KCl,组胺和去甲肾上腺素(NA)所致猪冠状动脉螺旋肌条的收缩效应。方法：利用猪冠脉条生物检定，分别加入10^-4mol/L和2×10^-4mol/L Hal于孵育液内，观察对KCl(10～50mmol/L)致猪冠脉条收缩量效曲线的影响。在KCl(20 mmol/L),组胺(10^-4mol/L)和NA(10^-4mol/L)分别致猪冠脉条收缩达最大效应时，加入10^-4mol/L Hal,观察对其收缩的阻断作用。结果：两种浓度Hal均可使冠脉条收缩曲线压低，并呈量效依赖关系。Hal可以阻断KCl,组胺和NA致冠脉条的收缩。在无钙孵育液内,Hal对KCl的阻断作用消失。多巴胺可使冠脉条呈显量效依赖的舒张。结论：Hal具有扩张冠脉的作用，此作用与多巴胺受体无关，但可能与钙有关。     

川芎嗪对心肌和冠状动脉机械电活动的影响

目的：观察川芎嗪对豚鼠乳头状肌机械电话动和猪冠状动脉收缩的影响。方法：标准玻璃微电极技术、电生理方法、血管灌流方法。结果：①川芎嗪（3.0μmol/L～100μmol/L）对豚鼠乳头状肌快反应电位（FAP）的时程（APD）、收缩力（FC）和慢反应电位（SAP）的幅度（APA），APD，FC及最大去极速度（V_max）均呈剂量依赖性抑制；②川芎嗪（3.0m mol/L）可以在高钾去极、钠通道失活的豚鼠乳头状肌标本上诱发产生SAP及FC，这一现象可被β受体阻断剂所阻断。［Ca²⁺］ｏ增加，川芎嗪诱发SAP的APA随之增加；③川芎嗪（10^-5mol/L～5×10^-3mol/L）对高钾去极化收缩的猪冠状动脉环呈舒张作用，且不被β受体阻断剂所阻断和［Ca²⁺］ｏ增加的影响。结论：提示川芎嗪可能通过β受体影响心肌细胞慢内向电流。川芎嗪对冠状动脉有舒张作用，此作用可能不是通过兴奋β受体而实现的。     

Pharmacological actions of the gut active principles in Croton penduliflorus hutch. Seed on isolated smooth and skeletal muscles and on blood pressure

The effects of Croton penduliflorus seed crystals (CP crystals) were investigated on isolated guinea-pig ileum, chick biventer cervicis muscle and frog rectus abdominis muscle. The effect of the crystals on flood pressure of normotensive Sprague Dawley rats was also investigated. CP crystals induced concentrations-dependent contractions in the guinea-pig ileum with EC₅₀ of 2.39 × 10⁶ g/mL. Contractions induced by CP crystals in the guinea-pig ileum were not inhibited by atropine (2 × 10^?7-1.2 × 10^?6 g/mL), tetrodotoxin (3 × 10^?8-2 × 10^?7 g/mL), hexamethonium (7 × 10^?6-2.8 × 10^?5 g/mL), mepyramine (2 × 10^?7 g/mL) and noradrenaline (2 × 10^?5 g/mL) but were completely (100%) inhibited by indomethacin (7.2 × 10^?6 g/mL). CP crystals (1.0 × 10^?6-5.0 × 10^?4 g/mL) could not elicit contractions in either chick biventer cervicis or frog rectus abdominis muscle. The mean blood pressure of normotensive Sprague Dawley rats was significantly reduced by CP crystals (1.6 × 10^?4-2.5 × 10^?3 g/mL) while the heart rate was significantly reduced by an intravenous infusion of the crystals (2.5 × 10^?3 g/kg) after 2min. The methods employed and the significance of the results obtained are discussed.     

Effects of crinum glaucum aqueous extract on intestinal smooth muscle activity

Crinum glaucum aqueous extract (1–8 mg/mL) produced a concentration dependent, non-competitive inhibition of contractions induced by acetylcholine (1.1 × 10⁻⁸–3.3 × 10⁻⁷M ) and calcium chloride (CaCl₂, 0.05–2 mM ) on the rat duodenum. Contractions of the guinea-pig ileum induced by acetylcholine (1.1 × 10⁻⁸–3.3 × 10⁻⁷M ) and histamine (1.1 × 10⁻⁸–3.3 × 10⁻⁷M ) were inhibited by the extract (1–4 mg/mL). The extract (0.125–2.0 mg/mL) also, produced a concentration dependent relaxation of the guinea-pig taenia coli, precontracted with potassium chloride (40 mM ). It is concluded that the extract is a non-specific relaxant of the gastrointestinal smooth muscles used. © 1998 John Wiley & Sons, Ltd.     

Different Effects of Some Isoquinoline Alkaloids from Argemone mexicana on Electrically Induced Contractions of Isolated Guinea-pig Ileum

The present study examines the effects of the extracts [petroleum ether, CHCl₃, CHCl₃/MeOH (9:1) and MeOH], partially purified fractions and pure compounds from Argemone mexicana on the electrically induced contractions of the isolated guinea-pig ileum (E.C.I.). The results of the experiments indicate that CHCl₃/MeOH (9:1) and MeOH extracts, tested at a concentration of 400, 200 and 100 μg/mL, dose-dependently reduced the guinea-pig ileum contractions, whereas the petroleum ether and CHCl₃ extracts did not affect it. Furthermore, the partially purified fractions II–V from the MeOH extract, each tested at concentrations of 200, 100 and 50 μg/mL also inhibited E.C.I. Finally the pure compounds 1–2 (5×10⁻⁶–1×10⁻⁵–5×10⁻⁵ M ) isolated and purified from the above fractions significantly reduced, in a dose dependent manner, the electrical contractions of the ileum, whereas compound 3 (5×10⁻⁶–1×10⁻⁵×10⁻⁵ M ) increased them. Since the active compounds 1–3 were respectively identified as protopine, allocryptopine and berberine by NMR, the observed effects could be related mainly to these compounds. © 1997 by John Wiley & Sons, Ltd.     

The source of ca2+ for the spasmolytic actions of longicaudatine,a bisindole alkaloid isolated from Strychnos trinervis (Vell.) Mart. (Loganiaceae)

Longicaudatine, a tertiary bisindole alkaloid isolated from the root bark of Strychnos trinervis (Vell.) Mart. (Loganiaceae), antagonized in a noncompetitive manner, carbachol and histamine induced contractions of the guinea-pig ileum and bradykinin responses in the rat uterus. The respective pD₂' values (mean ± SE) were 4.61 ± 0.21, 4.98 ± 0.04 and 4.49 ± 0.01. Longicaudatine, unlike verapamil, had no effect on voltage dependent Ca²⁺ channels, as it failed to inhibit KCI or CaCl₂ induced contractions of guinea-pig ileum and depolarized rat uterus respectively. When compared with sodium nitroprusside, an antagonist of receptor operated Ca²⁺ channels, longicaudatine produced a slower and weaker inhibition of noradrenaline induced sustained contractions of rabbit aortic strips. However, in the aorta, the alkaloid antagonized the intracellular calcium dependent transient contractions of noradrenaline and longicaudatine (IC₅₀, 5.01 × 10^?7 M) was approximately 133 times more potent that procaine (IC₅₀, 6.68 × 10^?5 M), a known inhibitor of the release of Ca²⁺ from intracellular stores. Longicaudatine may exert nonspecific spasmolytic effects by acting on intracellular Ca²⁺ stores, rather than on depolarization dependent or receptor operated Ca²⁺ channels.     

Spasmolytic actions of warifteine,a bisbenzylisoquinoline alkaloid isolated from the root bark of Cissampelos sympodialis Eichl. (menispermaceae)

Warifteine, a bisbenzylisoquinoline alkaloid isolated from the root bark of Cissampelos sympodialis Eichl., produced a reversible, nonspecific and noncompetitive antagonism of histamine, carbachol and bradykinin induced contractions of the guinea-pig ileum. The corresponding pD'₂ values (mean±SE) were 4.90±0.15, 4.95±0.20 and 5.03±0.11. Warifteine also antagonized oxytocin and bradykinin induced contractions of the rat uterus in a similar manner with pD'₂ values of 4.30±0.26 and 3.76±0.06 respectively. In the guinea-pig trachea, the alkaloid inhibited spontaneous tone (IC₅₀, 1.1 × 10^?5M) as well as carbachol induced sustained contractions (IC₅₀, 2.9 × 10^?5M). As warifteine antagonized KCI induced contractions of the guinea-pig ileum (pD'₂ value 4.57±0.10), inhibition of Ca⁺⁺ influx through voltage operated Ca⁺⁺ channels may be partially responsible for its antispasmodic activity. However, the reported local anaesthetic property of warifteine may not contribute to the observed muscle relaxation as procaine failed to reduce the spontaneous tone or consistently antagonize carbachol induced contractions of the trachea and was inactive in inhibiting voltage operated Ca⁺⁺ channels in the ileum.     

Inhibiting Activity of Some Glucoindolalkaloids and Iridoids from Sickingia williamsii on Electrically Induced Contractions of Isolated Guinea-pig Ileum

The present study examined the effects of the extracts (petroleum ether, CHCl₃, CHCl₃/MeOH (9:1) and MeOH), partially purified fractions and pure compounds (mainly alkaloids and iridoids) from Sickingia williamsii on the electrically induced contractions of the isolated guinea-pig ileum. The results of our experiments indicate that CHCl₃/MeOH (9:1) and CHCl₃ extracts, tested at concentrations of 300, 150 and 30 μg/mL, dose-dependently reduced the guinea-pig ileum electrical contractions, whereas MeOH and petroleum ether extracts did not affect it. Furthermore, both the partially purified fractions I–IV each tested at concentrations of 500, 250 and 100 μg/mL from the CHCl₃/MeOH (9:1) extract and some pure compounds (10⁻⁴ M , 5×10⁻⁵ M and 2.5×10⁻⁵ M ) isolated and purified from the above fractions significantly reduced, in a dose dependent manner, the electrical contractions of the ileum. As the active pure compounds possess an indole nucleus or/and an iridoid nucleus in their structures, the inhibitory effects appear to depend on these structures.     

梯度剂量巴豆霜药理作用初探

[目的]研究梯度剂量巴豆霜对肠道的作用.[方法]通过兔回肠吸收实验观察梯度剂量巴豆霜对回肠水液代谢的影响,按巴豆霜给药终浓度将兔回肠检体随机分为5组:巴1组:2.22x10-2kg/L、巴2组:4.44x10-2kg/L、巴3组:6.66x10-2kg/L、巴4组:4.45x10-1kg,L;对照组:0.9%生理盐水.观察时间2 h,比较各组水代谢剩余量.用番泻叶诱导腹泻模型,分为4组:正常组、模型组、巴1组(巴豆霜浓度8.33x10-4kg/L)、巴2组:(巴豆霜浓度1.67x10-3kg/L).比较各组稀便率、D-木糖吸收浓度及碳末推进率.[结果]与对照组比较巴1组、巴2组回肠水代谢剩余量减少(P<0.01):巴3组水代谢剩余量未见有意改变(P0.05);巴4组回肠水分增加(P<0.01).与对照组比较腹泻模型组大鼠稀便率升高(P<0.01)、血清D-木糖浓度降低、碳末推进率增加(P<0.05).与模型组相比,巴1组、巴2组稀便率降低、D-木糖浓度升高、碳末推进率降低(P<0.05),但2剂量组间未见显著性差异(P0.05).[结论]巴豆霜能显著增加回肠水液的分泌,但随剂量的递减表现出相反的作用:小剂量巴豆霜止泻作用与促进回肠水分吸收、降低病理性肠蠕动过快,改善肠吸收功能密切相关.     

Bisnordihydrotoxiferine and vellosimine from Strychnos divaricans root: Spasmolytic properties of bisnordihydrotoxiferine

Bisnordihydrotoxiferine and vellosimine, two tertiary indole alkaloids have been isolated from the root of Strychnos divaricans. Bisnordihydrotoxiferine antagonized in a nonspecific manner, oxytocin and acetylcholine induced contractions in the rat uterus and acetylcholine and histamine responses in the guinea-pig ileum. Bisnordihydrotoxiferine, like verapamil, produced effects on voltage dependent Ca²⁺ channels. For example in guinea-pig ileum, bisnordihydrotoxiferine (pD'₂ 3.92±0.09) and verapamil (pD'₂ 6.00±0.11) inhibited KCl induced contractions. Furthermore, bisnordihydrotoxiferine (pD'₂ 4.37±0.02) and verapamil (pD'₂ 6.83±0.10) also antagonized CaCl₂ induced contractions of K⁺-depolarized rat uterus. When compared with sodium nitroprusside, an antagonist of receptor operated Ca²⁺ channels, bisnordihydrotoxiferine had no effect. However, in the aorta, the alkaloid (IC₅₀, 6.10 × 10^?6M) antagonized the intracellular calcium dependent transient contractions of noradrenaline and it was about four times more potent than procaine (IC₅₀, 2.30 × 10^?5M), a known inhibitor of the release of Ca²⁺ from intracellular stores. Bisnordihydrotoxiferine may produce nonspecific spasmolytic actions mainly by inhibiting intracellular calcium mobilization and to a lesser extent by inhibiting voltage dependent calcium channels in smooth muscles.     

Effects of the flavone luteolin,isolated from Colchicum richii,on guinea-pig isolated smooth muscle and heart and on blood pressure and blood flow

The effects of the flavone luteolin, extracted from Colchicum richii, on guinea-pig isolated ileum, pulmonary artery, trachea, atrium, perfused heart, and on blood pressure and blood flow of anaesthetized guinea-pigs were studied. Luteolin (10^?5?3 × 10^?4 M) caused concentration-dependent relaxation of the tone of ileum, epinephrine-precontracted pulmonary artery and only mild relaxation of acetylcholine-precontracted trachea. These effects were not affected by pretreatment with 1 mM theophylline except in the ileum where theophylline shifted to the left the luteolin concentration-effect curve. Luteolin (3 × 10^?6?3 × 10^?4 M) caused an increase in the beating rate and the contractility of the spontaneously beating atrium and of the isolated perfused heart. Theophylline (1 mM) significantly inhibited the effects of luteolin on the atrium and the perfused heart. Luteolin, in doses of 0.3, 1.0, 1.5 and 5 mg/kg body weight had no effect on heart rate of anaesthetized guinea-pigs but caused depression of systolic and diastolic blood pressure except at the lowest dose used where there was a small increase in both parameters. Also, only the lowest dose (0.3 mg/kg) caused a small increase in blood flow. Larger doses of luteolin caused dose-related inhibition of blood flow. The effects of luteolin on blood pressure and blood flow were not affected by theophylline pretreatment (5 mg/kg). These observations suggest that the effects of luteolin may be tissue-specific and in the isolated heart they may be attributed to inhibition of cyclic AMP phosphodiesterase. The data further demonstrate that luteolin has potential cardiovascular effects that merit further investigation.     

Smooth muscle relaxant activities of compounds isolated from malaysian medicinal plants on rat aorta and guinea-pig ileum

Muscle relaxant activities of six compounds isolated from Malaysian medicinal plants were investigated on the smooth muscles of the rat aorta and longitudinal muscle of the guinea-pig ileum. Except for goniothalamin, the other five compounds exhibited varying degrees of muscle relaxant activities on the two smooth muscles. Dicentrine, isocorydine, altholactone and usnic acid reduced the contractions to KCI and phenylephrine in the rat aorta, whilst atranorin slightly reduced the contractions to phenylephrine but not KCI. In addition, dicentrine and isocorydine markedly reduced the contractile response to phenylephrine in Ca²⁺-free Krebs solution. In the longitudinal muscle of the guinea-pig ileum, altholactone, atranorin, dicentrine and isocorydine inhibited to a greater extent the phasic than the tonic responses to KCI. All four compounds similarly inhibited the contractions induced by ACh. The results suggest that the relaxant activities of the compounds are attributed mainly to inhibition of Ca²⁺ influx via the calcium channels in the membrane of the smooth muscles. Furthermore, the greater sensitivity of dicentrine, isocorydine and altholactone against phenylephrine-induced contractions or KCI-induced phasic contractions are due to their abilities to inhibit intracellular Ca²⁺ release in these muscles.