pD2-, pA2- and pD2'-values of a series of compounds in a histaminic and a cholinergic system.

(1) Affinity and intrinsic activity values of 75 compounds for a histaminergic and a cholinergic system are presented. The quantitative correlations between the affinity values of 35 compounds and some physicochemical constants (Van der Waals volume, lipophilicity, number of hydrogen atoms on the protonated amine) are discussed. (2) Absence of systematic differences between pD2 and pA2 of partial agonists supports the assumption that these values are equivalent expressions of the same affinity. (3) The "mimetic moiety" in a number of the antihistaminic test compounds hardly contributes to their affinity. The affinity mainly depends on an interaction tendency with additional receptor areas. (4) The correlation between pA2 and pD2' of the whole series of compounds in the histaminergic system is artificial. The method only allows determination of both values if their ratio lies between certain limits. (5) The correlation between pA2 and pD2' for 16 closely related compounds in the guinea pig ileum and for nearly all compounds in the rat intestine has to be explained by an influence of the structural differences on drug transference and/or the less specific binding forces. (6) The metactoid receptors in the two systems are different structures. (7) Possible molecular modifications to maximize the separation of antihistaminic form cholinergic affinity are suggested.     

甘草酸两种异构体治疗肾综合征出血热的疗效观察

目的 :比较甘草酸两种异构体治疗肾综合征出血热 (HFRS)的临床效果。方法 :HFRS患者78例 ,随机分为A、B两组。A组加用甘草酸α体制剂 (甘利欣 )静脉滴注 ,B组加用甘草酸β 体制剂 (美能 )静脉滴注。观察两组越期率等多项临床指标并进行比较。结果 :两组治疗后 ,除丙氨酸氨基转移酶复常时间无差异外 ,其余观察指标均存在显著性差异 ,B组疗效优于A组 (P<0 01)。结论 :临床治疗HFRS ,甘草酸 β体制剂疗效显著优于甘草酸α体制剂     

治疗阿尔采末病的药物靶点:β-分泌酶

近年来的研究表明,β-淀粉样蛋白(Aβ)是老年斑的主要成分,有明显的神经细胞毒性作用,在阿尔采末病(AD)的发病过程中发挥了重要作用,因此降低脑中Aβ的生成量是治疗AD的策略。Aβ是由β-和γ-分泌酶裂解其前体蛋白(APP)而生成,其中β-分泌酶(BACE)是启动Aβ形成的关键限速酶,因此BACE是开发治疗AD药物的一个具有吸引力的作用靶点。该文就近来对β-分泌酶的研究作一综述。     

TGF-β和IGF表达异常与滋养层相关疾病关系的研究

目的:探讨转化生长因子(TGF-β)和胰岛素样生长因子(IGF)等与滋养层侵入调节密切相关的细胞因子在胎盘绒毛组织中的表达,及与葡萄胎、先兆子痫等滋养层细胞相关妊娠疾病病理机制的关系。方法:采用半定量逆转录多聚酶链反应(RT-PCR)检测方法,分别以正常早孕绒毛和正常足月(自然分娩或剖宫产)胎盘绒毛组织为对照,观察葡萄胎组织与先兆子痫足月胎盘绒毛组织中TGF-β和IGF的表达。结果:5种胎盘绒毛组织中均可检测到IGF-I mRNA的表达,且先兆子痫足月胎盘绒毛组织中IGF-I的表达量明显低于正常足月胎盘绒毛组织,而葡萄胎组织中IGF-I的表达略高于正常早孕绒毛。在3种足月胎盘绒毛组织中可检测到IGF-ⅡmRNA的表达,但相互之间无明显差异。葡萄胎组织中IGF-Ⅱ的表达低于早孕绒毛。5种胎盘绒毛组织中均有TGF-β3的表达,而TGF-β1和TGF-β2的表达并未检测到。在表达量上,葡萄胎组织中TGF-β3的表达明显高于正常早孕绒毛组织,先兆子痫胎盘绒毛组织中TGF-β3的表达强于足月自然分娩的正常胎盘绒毛组织,而剖宫产胎盘绒毛组织中,TGF-β3的表达亦相对较强。结论:TGF-β3和IGF-I在胎盘绒毛组织中的表达变化,可能和葡萄胎、先兆子痫等与滋养层密切相关的妊娠疾病的发生有关。     

雷公藤内酯醇抑制大鼠脑局灶性缺血再灌注后脑组织IL-1βmRNA表达的研究

目的　观察雷公藤内酯醇 (Triptolide ,TL)对局灶性脑缺血再灌注大鼠脑组织内IL 1βmRNA水平变化的影响 ,探讨雷公藤内酯醇对大鼠局灶性缺血再灌注脑损伤保护作用的机制。方法　建立大鼠局灶性脑缺血再灌注模型 ,观察应用雷公藤内酯醇 (0 2和 0 4mg·kg-1)对大鼠脑组织微血管内附壁中性粒细胞计数 ,以及神经功能受损程度的影响。应用RT PCR技术 ,检测大中动脉闭塞侧脑组织IL 1βmRNA表达水平的变化情况。结果　与对照组比较 ,雷公藤内酯醇两治疗组大脑中动脉闭塞侧微血管内附壁中性粒细胞计数、脑组织IL 1βmRNA水平均明显下降。神经功能受损程度也明显改善。结论　雷公藤内酯醇具有明显抑制缺血再灌注大鼠脑组织内IL 1βmRNA表达、降低IL 1β含量和抑制白细胞浸润的作用。这可能是雷公藤内酯醇对大鼠缺血再灌注脑损伤保护作用的机制之一     

银杏内酯B对血小板活化因子刺激的大鼠中性粒细胞功能的影响银杏内酯B对血小板活化因子刺激的大鼠中性粒细胞功能的影响

目的 研究银杏内酯B对血小板活化因子(PAF)刺激的大鼠中性粒细胞粘附、趋化及脱颗粒功能的影响。方法 从大鼠外周血分离中性粒细胞,用MTT比色法、Boyden小室法及β-葡萄糖苷酸酶释放法分别检测PAF诱导的粒细胞粘附、趋化及脱颗粒反应。结果10 μmol·L^-1 银杏内酯B可显著抑制中性粒细胞的粘附反应;1～1 000 nmol·L^-1 可剂量依赖性抑制10 nmol·L^-1 PAF诱发的粒细胞趋化反应,其IC₅₀为4.84 nmol·L^-1; 0.01～10 μmol·L^-1可抑制1 μmol·L^-1 PAF诱发的粒细胞释放β-葡糖苷酸酶,其IC₅₀为3.56 μmol·L^-1。结论银杏内酯B能够抑制PAF刺激的大鼠中性粒细胞粘附、趋化及脱颗粒反应。     

β-细辛醚在大鼠体内的药代动力学

目的了解石菖蒲主要成分β-细辛醚的药代动力学特征。方法以HPLC法测定ig大鼠血清和各器官（脑、心、肺、肾、肝）中β-细辛醚的浓度，把器官当作相对独立的系统，用DAS软件进行药代动力学分析。结果β-细辛醚在大鼠体内的药代动力学过程属一级一室动力学模型，血清半衰期为54 min；达峰时间12 min；达峰浓度3.19 mg·L^-1。各器官与血清有相似的动力学过程。结论β-细辛醚在体内吸收、分布、代谢较迅速，极易透过血脑屏障，大脑是重要的分布器官。     

Effect of Complexation with Hydroxylpropyl-β-Cyclodextrin on Solubility, Dissolution Rate and Chemical Stability of Prostaglandin E1

Aim To study the effect of complexation with hydroxylpmpyl-β-cycledextrin (HP-β-CD) on the solubility, dissolution rate and chemical stability of pmstaglandin E1 (PGE1), thereby providing a basis for preparing a stable solid or aqueous preparation of PGF1 formulated with HP-β-CD. Methods The effect of HP-β-CD on the solubility of PGF1 was studied by phase solubility method. The formation of inclusion complexes of PGE1 with HP-β-CD in the aqueous solution was confirmed by UV spectra, circular dichroism spectroscopy, and that in the solid state by IR spectra and X-ray diffractometry. An solid inclusion complex of PGF1 with HP-β-CD was prepared by lyophilization. The dissolution rate and stability of the inclusion complex were determined and compared with those of PGE1 alone. Meanwhile, the stability of PGF1 aqueous solutions in the presence of HP-β-CD was studied under different pH conditions. Results The solubility of PGF1 increased linearly with increasing HP-β-CD concentration in various pH buffered solutions, showing typical AL-type phase solubility diagrams. The stability and dissolution rate of the solid inclusion complex of PGE1 were significantly increased, compared with those of pure PGE1 . The stability of PGEI in HP-β-CD solutions was also obviously improved under acidic and basic conditions, but the stabilizing effect was absent under neutral conditions. Conclulsions The solubility, dissolution rate and chemical stability of PGE1 are markedly improved by complexation with HP-β-CD. It is quite possible to prepare a stable PGE1 inclusion complex-containing solid dosage forms, but almost impossible to obtain a stable aqueous preparation of PGE1 formulated with HP-β-CD.     

石菖蒲挥发油、β-细辛醚对高脂血症大鼠血管舒缩与抗血小板聚集的作用

目的研究石菖蒲挥发油、β-细辛醚对高脂血症模型动物血管舒缩与抗血小板聚集的作用。方法大鼠喂养高脂饲料造成高脂血症模型,采用流式细胞术检测血液中 CD_(62p)、CD_(63)表达率,并用放免法测定脑组织中内皮素(ET)、降钙素基因相关肽(CGRP)、神经肽 Y(NPY)的舍量。结果石菖蒲挥发油能降低脑ET 的含量而升高脑 CGRP 的浓度;β-细辛醚能降低血 CD_(62p)表达率、降低脑 ET、NPY 的含量。结论石菖蒲挥发油、β-细辛醚有舒张血管、抗血小板聚集活性的作用。     

健脑安对血管性痴呆大鼠海马区IL-1β和CRF蛋白异常表达的影响

目的观察具有益气补肾活血化痰作用的中药提取物健脑安对血管性疾呆(VaD)大鼠海马区表达升高的白细胞介素1β(interleukin-1,IL-1β)、促肾上腺皮质激素释放因子(corticotropin-releasing factor,CRF)的影响。方法对 Koizumi 和 Nagasawa 法加以改进,采用同侧颈总动脉永久结扎线栓法制备大脑中动脉梗塞(MCAO)大鼠模型,2h 后实现大脑中动脉再灌。动物分成中药健脑安大(19.34g 生药/ml)、中(9.67g 生药/ml)、小(4.83g 生药/ml)剂量组、白细胞介素1受体拮抗剂(IL-1ra)对照组、模型组和假手术组。中药干浸膏用0.5%羧甲基纤维素(CMC)配咸水溶液,每100g 大鼠给中药溶液0.7ml;IL-1ra 对照组大鼠在缺血前30min和缺血后10min 左侧脑室内分别注射人重组 IL-1ra 10μg;3个中药剂量组、假手术组、模型组分别于造模7天前开始灌胃中药及清洁水,分别按照缺血再灌后不同时间点(2、3、4、12h 和7天)取材。应用免疫组化方法标记实验各组大鼠脑海马区组织中 IL-1β和 CRF 蛋白阳性神经元的数量。结果...