萘哌地尔衍生物YMⅢ扩张血管效应及其机制研究

目的观察萘哌地尔衍生物YMⅢ对家兔血管活动的影响并探讨其血管活性机制,为该药的开发研究提供基础资料。方法采用家兔胸主动脉条收缩的方法,观察YMⅢ对去甲肾上腺素(NA)、5-羟色胺(5-HT)、和高钾缩血管量效曲线的影响;应用无Ca2+-复Ca2+的实验法,以NA和咖啡因为血管收缩剂,间接观察YMⅢ对细胞内游离钙浓度([Ca2+]i)的影响,并分析其可能作用的钙通道。结果YMⅢ10-8、5×10-8、10-7mol·L-1使NA量效曲线明显平行右移,而最大反应不变,pA2值为8.00;本品10-6、5×10-6mol·L-1对氯化钾(KCl)量效曲线没有明显影响,但当浓度为10-5mol·L-1时,能使高钾量效曲线呈非平行右移,最大反应压低,pD′2值为4.26;本品10-7、10-6、10-5mol·L-1虽使5-HT量效曲线的最大反应有降低趋势,但无统计学意义。在无钙Krebs液中,YMⅢ10-8、5×10-8、10-7mol·L-1呈浓度依赖性抑制NA所致血管条的短暂收缩,对复钙后NA所诱发的持续性收缩也呈浓度依赖性抑制作用,但其剂量达10-5mol·L-1时尚不能抑制咖啡因在无Ca2+液中所致收缩。结论YMⅢ可能是一种α受体阻断剂,其扩血管机制可能是阻断细胞膜上的α受体,从而抑制受体中介的Ca2+内流和Ca2+释放。     

萘哌地尔衍生物(BWYJ)对血管平滑肌细胞游离钙浓度的影响

目的:观察萘哌地尔衍生物(BWYJ)对家兔血管平滑肌细胞游离钙浓度的影响,对其血管活性进行机理探讨,进一步明确其作用机制。方法:采用钙荧光指示剂Fura-2/AM负载的培养家兔胸主动脉平滑肌细胞,观察该药对NA、5-HT和高钾所致的[Ca2 ]i的升高的影响。结果:Fura-2/AM负载血管平滑肌细胞的实验中,静息时各浓度的BWYJ对[Ca2 ]i无明显影响,但其对NA和5-HT所引起的血管平滑肌[Ca2 ]i增加均有明显的抑制作用,而不影响高钾所致血管平滑肌[Ca2 ]i的增加。结论:BWYJ通过阻断细胞膜上的α1受体或5-HT2A受体,抑制这些受体中介的钙内流,从而抑制细胞内Ca2 的释放,使血管平滑肌[Ca2 ]i降低。     

灯盏花素抑制去甲肾上腺素而增强高钾缩血管反应

目的　观察灯盏花素 (Bre)对去甲肾上腺素 (NA)和高钾所致缩血管反应的影响 ,研究其效应与细胞内游离钙浓度([Ca2 + ]i)变化的关系。方法　采用兔胸主动脉条 ,观察Bre对NA及高钾缩血管量效曲线、对NA和咖啡因在无钙液中所致短暂收缩及复钙后NA缩血管反应的影响 ;利用Fura 2 /AM负载的兔血管平滑肌细胞 ,观察在Bre存在下 ,由NA及高钾所增加的 [Ca2 + ]i的变化。结果　Bre呈剂量依赖性地使NA缩血管量效曲线非平行右移 ,最大反应压低 ,对高钾的量效曲线却呈增强作用 ;该药抑制NA及咖啡因在无Ca2 + 液中所诱发的短暂收缩及复Ca2 + 后NA所致缩血管反应 ;Bre抑制NA所致平滑肌 [Ca2 + ]i 的升高 ,而增强高钾升高 [Ca2 + ]i 的作用。结论　Bre通过抑制Ca2 + 内流和Ca2 +释放而抑制NA所致血管平滑肌的收缩 ,通过增强高钾所致Ca2 + 内流而增强其缩血管效应 ,但Bre增强高钾升高[Ca2 + ]i 的作用原理尚有待探讨     

东莨菪碱扩血管作用机制研究

用离体血管环研究了东莨菪碱扩血管作用的机制。结果表明 ,东莨菪碱预处理不影响高钾引起的家兔主动脉环收缩 ,但可明显抑制去甲肾上腺素、组织胺及 5 -羟色胺分别引起的收缩 ,去除血管内皮不影响这种抑制作用。     

甘草酸三铵盐对兔胸主动脉条收缩反应的影响

甘草酸三铵盐（TAGA）非竞争性对抗去甲肾上腺素（NA）和氯化钾（KO）对离休兔胸主动脉条的收缩效应，PD2（NA）＝6．2426±0．3508，PD’2（TAGA）＝1．7844±0．3645。TAGA同时促进低浓度KCl（10mMol／L）收缩动脉条作用，表现为双向作用。TAGA使NA所致动脉条收缩发生舒张，且作用持久。在给KCl之前，先给TAGA，TAGA抑制KCl的收缩作用。     

淫羊藿甙扩血管作用机制的研究

本实验以离体兔胸主动脉条为标本，对淫羊藿甙（ＥＩ）扩血管作用的机制进行了探讨。ＥＩ２０，４０ｍｇ·Ｌ－１对ＮＥ、ＫＣｌ及ＣａＣｌ２收缩兔主动脉条的量效曲线呈非竞争性拮抗作用；ＥＩ３０ｇ·Ｌ－１能明显抑制ＮＥ诱导的兔主动脉条依赖于细胞外钙的收缩反应，对依赖于细胞内钙的收缩反应没有影响；ＥＩ３０ｇ·Ｌ－１松驰主动脉条的作用与阻断α受体或激动β受体无关。提示ＥＩ的扩血管作用机制可能与其对钙通道的阻滞作用有关。     

西洋参茎叶皂甙对离体家兔胸主动脉条的作用

西洋参茎叶皂甙对离体家兔胸主动脉条的作用吴捷，于晓江，刘传镐（西安医科大学临床药理研究所，西安７１００６１）西洋参茎叶皂甙（ｓａｐｏｎｉｎｓｏｆＰａｎａｘｑｕｉｎｑｕｅ－ｆｏｌｉｕｍｌｅａｆａｎｄｓｔｅｍ，ＳＰＱ）系从西洋参地上部分提取的总皂甙，具有...     

萘哌地尔衍生物YMⅢ对自发性高血压大鼠血管平滑肌细胞增殖的影响及其机理研究

目的：本实验旨在观察萘哌地尔衍生物YMⅢ对体外培养的自发性高血压大鼠（SHR）及Wistar大鼠胸主动脉平滑肌细胞（VSMC）增殖的影响，为该药的开发研究提供基础资料。方法：（1）将SHR及Wistar大鼠胸主动脉平滑肌细胞进行体外培养，以SHR胸主动脉平滑肌细胞为研究对象，以Wistar大鼠作对照。（2）应用四甲基偶氮唑盐（MTT）微量酶反应法检测细胞增殖活性；real-time PCR技术检测其对Agt、     

A型行为与冠心病相关性研究

目的　探讨血浆去甲肾上腺素 (NE)、肾上腺素 (E)、5 -羟色胺 (5 - HT)浓度与 A型行为冠心病的关系及临床意义。方法　对 6 0例确诊为冠心病的患者进行 A型行为问卷测试 ,分为 A型组 32例 ,B型组 2 8例。用酶联免疫吸附法 (EL ISA)测定血浆中 NE、E、5 - HT浓度。结果　 TH +CH值与 NE、E、5 - HT呈正相关 (r值分别为 0 .5 5 9、0 .5 0 6、0 .4 13,P<0 .0 0 1) ,提示 NE、E、5 - HT与 A型行为呈正相关。结论　 A型行为是发生冠心病的独立危险因素。测定血浆 NE、E、5 - HT浓度可为 A型行为冠心病的诊断和治疗提供可靠的、客观的实验室依据     

新型抗抑郁药治疗抑郁症的对照研究

目的：比较研究新型抗抑郁药治疗抑郁症的疗效。方法将187例抑郁症患者分为3组,分别给予三类新型抗抑郁药单药治疗（ A组：舍曲林、艾司西酞普兰和帕罗西汀,B组：文拉法辛、度洛西汀,C组：米氮平）,疗程共4周。采用17项汉密尔顿抑郁量表（ HDRS-17）作疗效评定,量表减分率≥50％为治疗有效,量表总分≤7分为痊愈。结果3组间基线资料差异无显著统计学意义（ P＞0.05）。终点时治疗有效127例（67.9％）,痊愈75例（40.1％）。3组药物间治疗有效率（χ^2＝1.336,P＝0.513）、痊愈率（χ^2＝1.988,P＝0.370）的差异均无显著性统计学意义。治疗4周后,各组患者的HDRS-17评分及减分率的差异均有显著统计学意义（F＝665.33和496.89,P＜0.05）,3组间各周HDRS-17评分及减分率的差异均无显著统计学意义（F＝2.01和1.36,P＞0.05）。结论新型抗抑郁药物治疗抑郁症均有较好、相当的疗效。     

萘哌地尔衍生物BWYJ对大鼠血压及猫血流动力学的影响

目的:观察萘哌地尔衍生物BWYJ对高血压模型和正常大鼠血压及猫血流动力学的影响。方法:分别对高血压和正常大鼠静脉及灌胃给药,观察血压变化;利用麻醉开胸测定猫血流动力学的变化;采用侧脑室给药、猫在体瞬膜神经肌肉标本初步探讨降压机制。结果:BWYJ1.2及2.4mg·kg-1iv,降低正常及高血压大鼠收缩压(SAP)和舒张压(DAP),且随剂量的增加效应增加,作用时间延长。BWYJ10、20及40mg·kg-1灌胃给药,降低清醒正常大鼠SAP(最大效应分别下降4.6%、13.0%、16.8%)和DAP(分别下降7.1%、17.9%、20.5%),3h后恢复。BWYJ5、10及20mg·kg-1灌胃清醒高血压大鼠,降低SAP(下降7.3%、16.5%、20.4%)和DAP(8.5%、14.8%、24.5%),强于正常大鼠且时间明显延长。麻醉猫十二直肠给药,BWYJ2.5mg·kg-1仅DAP、LVWI降低,BWYJ5mg·kg-1使SAP、DAP、TPR、±dp/dtmax及LVWI明显降低,其他无明显变化。结论:BWYJ静脉或灌胃给药对正常和肾性高血压大鼠产生降压作用,降压作用与中枢、神经节无关。     

Frequency-Dependence of the Metabolism of 3H-Noradrenaline Released from Rabbit Isolated Aorta: Effects of a Combination of Cocaine and Corticosterone or Hydrocortisone

Abstract The effect of cocaine (neuronal uptake inhibitor) in combination with either hydrocortisone or corticosterone (extraneuronal uptake inhibitors) on the metabolism of ³H-noradrenaline (³H-NA) released spontaneously or by electrical-field stimulation was studied on the isolated rabbit aorta preloaded with ³H-NA. In the spontaneous outflow ³H-O-methylated and deaminated metabolites (³H-OMDA) accounted for 41% of the total radioactivity whereas ³H-NA represented only 22%. Cocaine (3 × 10^-5M) + hydrocortisone (10^-4 M) neither changed the spontaneous outflow of total tritium nor the distribution of the ³H-outflow on ³H-NA and its ³H-metabolites. However, cocaine (3 × 100^-5M) + corticosterone (4 × 10^-5M) enhanced the passive ³H-outflow, increased the percentage recovered as ³H-3,4-dihydroxyphenylglycol (³H-DOPEG), and reduced the percentage of ³H-OMDA + ³H-NMN. The effect of field-stimulation was investigated during and ofter stimulation at two frequencies: 3 and 10 Hz. The stimulation-induced ³H-overflow consisted mainly of unmetabolized ³H-NA and ³H-OMDA in the sample collected during stimulation. The ratio between ³H-NA and ³H-OMDA was strongly dependent on the frequency of stimulation, Thus it was 1:2 at 3 Hz, but 3:1 at 10 Hz. These ratios were about the same during the poststimulation period. On the other hand, whereas the formation of ³H-DOPEG from ³H-NA released during stimulation at both frequencies was small, it increased rapidly in the poststimulation sample. At 3 Hz, inhibition of neuronal and extraneuronal uptake by cocaine + steroids did not change the stimulation-induced ³H-overflow, but the distribution on ³H-NA and ³H-metabolites was markedly altered. Thus the percentage of ³H-N A was doubled, ³H-OMDA was halved, and ³H-DOPEG was almost abolished. At 10 Hz, however, cocaine + corticosterone decreased the stimulation-induced ³H-overflow, but did not change the proportions of ³H-NA and ³H-OMDA. Only the formation of ³H-DOPEG was markedly reduced. It is concluded that the distribution of stimulation-induced ³H-overflow on ³H-NA and its ³H-metabolites and the effect of neuronal and extraneuronal uptake inhibition on this is strongly influenced by the frequency of stimulation. Furthermore, inhibition of both neuronal and extraneuronal uptake does not fully prevent metabolism of ³H-NA released by electrical-field stimulation.     

异紫堇啡碱对血管平滑肌钙内流和钙释放的影响

目的研究异紫堇啡碱（ＩＳＯＣ）对血管平滑肌钙内流和钙释放的影响，以初步阐明其作用方式。方法利用兔胸主动脉螺旋条标本观察ＩＳＯＣ对去甲肾上腺素（ＮＡ）及ＫＣｌ量效曲线的影响和对无钙液中ＮＡ、ＣａＣｌ２复钙、咖啡因缩血管效应的影响。结果ＩＳＯＣ１０μｍｏｌ·Ｌ－１对ＮＡ的量效曲线呈非竞争性拮抗作用，而对高钾的作用则不明显。在无钙液中，ＩＳＯＣ１００μｍｏｌ·Ｌ－１能明显抑制ＮＡ所致的收缩及复钙后外钙内流诱发的收缩，ＩＳＯＣ１０及３０μｍｏｌ·Ｌ－１则只作用于前者；各实验浓度的ＩＳＯＣ对咖啡因在无钙液中的缩血管作用均无影响。结论ＩＳＯＣ抑制受体中介的钙释放和钙内流，但不是典型的钙拮抗剂。     

Effect of Cocaine and Corticosterone on the Metabolism of 3H-Noradrenaline Released from Rabbit Isolated Aorta and Adventitia

Abstract: The effect of cocaine and corticosterone (neuronal and extraneuronal uptake inhibitors, respectively) on the metabolism of ³H-noradrenaline (³H-NA) released spontaneuosly or by electrical-field stimulation was studied in the rabbit isolated aorta and tunica adventitia preloaded with ³H-NA. The spontaneous outflow of tritium from untreated aorta consisted of ³H-NA (25%); ³H-3,4-dihydroxyphenylglycol (³H-DOPEG; 24%); ³H-3,4-dihydroxymandelic acid (³H-DOMA; 8%); ³H-O-methylated plus deaminated compounds (³H-OMDA; 45%); and ³H-normetanephrine (³H-NMN; 1%). The percentage distribution of ³H-NA and its ³H-metabolites in this outflow was not altered by either cocaine (3 × 10^?5 M), corticosterone (4 × 10^?5 M), or cocaine (3 × 10^?5 M) + corticosterone (4 × 10^?5 M). The spontaneous ³H-outflow from untreated tunica adventitia did not differ from that of aorta. Cocaine (3 × 10^?5 M) + corticosterone (4 × 10^?5 M) did not alter the composition of ³H-NA and its ³H-metabolites in the spontaneous outflow from adventitia. The stimulation-evoked ³H-overflow from untreated rabbit aorta preloaded with ³H-NA consisted of ³H-NA (40%); ³H-DOPEG (15%); ³H-DOMA (2%); ³H-OMDA (50%); and ³H-NMN (3%). Cocaine (3 × 10^?5 M) decreased the percentage recovered as ³H-DOPEG, increased ³H-NMN and had no effect on the other ³H-metabolites. Corticosterone (4 × 10^?5 M) had no effect on the percentage distribution of ³H-NA and its ³H-metabolites. Cocaine (3 × 10^?5 M) + corticosterone (4 × 10^?5 M) increased ³H-NA, decreased ³H-DOPEG and had no effect on the percentage distribution of the other ³H-metabolites. In the case of adventitia, cocaine (3 × 10^?5 M) + corticosterone (4 × 10^?5 M) only decreased the percentage recovered as ³H-DOPEG, without any significant effect on ³H-NA and its other ³H-metabolites. It is concluded that inhibition of neuronal plus extraneuronal uptake of H-NA by cocaine plus corticosterone, respectively does not fully prevent metabolism of ³H-NA released either spontaneously or by electrical-field stimulation.     

心脉隆注射液对不同状态大鼠离体胸主动脉的影响

摘 要 目的：探讨心脉隆注射液（XML）对不同状态大鼠离体胸主动脉的影响。方法: 采用累积加药法,观察XML对静息、氯化钾（KCl）或去甲肾上腺素（NA）预收缩大鼠离体胸主动脉的影响。使用不同工具药分析作用产生的机制。结果: 与对照组相比,XML在一定浓度范围内可以兴奋静息离体胸主动脉,进一步增加KCl预收缩血管的张力,而降低NA预收缩血管的张力。XML舒张NA预收缩血管的作用可被普萘洛尔、双氯芬酸所抑制,而不受Nω-硝基-L-精氨酸的影响。结论:XML对不同状态下大鼠离体胸主动脉的作用不同,其机制可能与Ca²+通道、β受体和前列腺素有关。     

二氢石蒜碱对家兔脑血管的选择性作用

目的　观察二氢石蒜碱 (dihydrolycorine ,DL)对家兔脑血管的选择性作用。方法　采用家兔离体基底动脉(BA)、胸主动脉 (TA)及心室乳头肌 (PM)标本 ,记录药物对其张力的影响。结果　DL使BA静息张力升高 ,尼莫地平(Nim)则使其降低 ,对TA无影响。NA、KCl所致BA及TA收缩 ,DL使之呈剂量依赖性松弛 ,其IC50 值 :对BA分别为(6 6 9± 3 12 )× 10 -4、(3 4 1± 1 5 2 )× 10 -3 mol·L-1;对TA分别为 (1 4 9± 0 5 9)× 10 -3 、(2 91± 0 99)× 10 -3 mol·L-1。拮抗NA所致基底动脉收缩作用强于KCl。Nim对KCl所致收缩的抑制强于对NA。DL或Nim对电刺激诱发PM的收缩均有剂量依赖性抑制作用 ,DL对电刺激诱发PM收缩的IC50 值高于NA所致BA收缩IC50 值。结论　DL对BA有明显的选择性作用 ,在BA可能存在使该血管平滑肌收缩的α1受体亚型和使之舒张的 β受体。DL作用可能与对这些受体的阻断作用相关。这些选择性作用可能有助于改善缺血区的脑血流