酪氨酸单用及合并RU486对小鼠生殖功能的影响及作用机理

用小鼠抗早孕实验及体外大鼠黄体细胞培养的方法，研究酪氨酸单用及酪氨酸与已知抗生育药ＲＵ４８６合并用药对小鼠早期妊娠的影响及作用机制。结果表明，酪氨酸与ＲＵ４８６合用有协同抗早孕作用。进一步的机理研究发现，酪氨酸１７０ｍｇ·ｋｇ－１·５ｄ可使早孕小鼠血清孕酮水平显著降低；酪氨酸５０μｇ·ｍｌ－１与（＋）ＰＧ０５合用；对抑制大鼠黄体细胞孕酮的基础分泌有协同作用，并能显著抑制ｈＣＧ诱导的大鼠黄体细胞孕酮的分泌。结果提示：降低孕酮分泌可能是酪氨酸抗生育作用的途径之一。     

消旋(15R)-15甲基PGE2甲酯(PG6E)对大鼠实验性胃溃疡的保护作用

用实验性胃溃疡模型研究了PG₆E的抗溃疡作用,结果表明PG₆E有抗胃酸分泌作用,而对胃肠运动无明显影响;PG₆E在剂量为10～80μg·kg^-1时,对无水乙醇型、盐酸型、消炎痛型、慢性醋酸型和幽门结扎型胃溃疡有明显保护作用,并能显著减少幽门结扎大鼠的胃液体积、胃酸分泌、胃蛋白酶活性和DNA含量。小鼠poPG₆E30～60μg·kg^-1,3d后粘膜氨基己糖含量显著增加。研究结果提示PG₆E能抑制对胃粘膜的攻击性因素,增加保护性因素的作用,可望成为一种新型抗胃溃疡药。     

人参皂甙Rh_2体外对小鼠黑色素瘤细胞的分化诱导作用

体外实验证明人参皂甙Ｒｈ＿２在１０μｇ·ｍｌ￣（－１）的浓度下能明显抑制Ｂ＿（１６）细胞的生长，并呈浓度依赖性，其ＩＣ＿（５０）为４．１μｇ·ｍｌ￣（－１）。Ｒｈ＿２在１０μｇ·ｍｌ￣（－１）浓度下对Ｂ＿（１６）细胞有较强的分化诱导作用，表现为黑色素生成能力明显增加；形态向上皮样细胞分化；细胞呈网状结构；黑色素颗粒增多，生长变缓慢。细胞动力学研究结果表明，Ｒｈ＿２可使Ｂ＿（１６）细胞阻断在Ｇ＿１期。提示Ｒｈ＿２对Ｂ＿（１６）细胞具有分化诱导作用     

消旋15（R）－15－甲基PGE_2甲酯的合成

消旋１５（Ｒ）－１５－甲基ＰＧＥ＿２甲酯的合成金碧燕，吴元鎏，张守仁，徐瑞明（中国医学科学院、中国协和医科大学药物研究所，北京１０００５０）前列腺素是一类存在于人体内，有广泛生理活性的重要内源性物质。ＰＧＥ衍生物已被证实除有抑制胃酸及胃泌素分泌的作用...     

10－羟基癸烯酸抗大鼠胃溃疡作用

１０－羟基癸烯酸（１０－ＨＤＡ）抑制应激、结扎幽门和消炎痛性胃溃疡的形成．促进醋酸性胃溃疡的愈合。并且能抑制胃酸分泌．具有剂量依赖关系，促进胃壁结合粘液．胃组织ＤＮＡ、ｃＡＭＰ和胃粘膜前列腺素Ｅ２含量增加．提示．１０－ＨＤＡ抗胃溃疡作用可能与其抑制胃酸分泌及增强胃粘膜细胞保护作用有关。     

10－羟基癸烯酸抗大鼠胃溃疡作用

１０－羟基癸烯酸（１０－ＨＤＡ）抑制应激、结扎幽门和消炎痛性胃溃疡的形成．促进醋酸性胃溃疡的愈合。并且能抑制胃酸分泌．具有剂量依赖关系，促进胃壁结合粘液．胃组织ＤＮＡ、ｃＡＭＰ和胃粘膜前列腺素Ｅ２含量增加．提示．１０－ＨＤＡ抗胃溃疡作用可能与其抑制胃酸分泌及增强胃粘膜细胞保护作用有关。     

消旋(15R)-15甲基PGE2甲酯(PG6E)对在体大鼠胃酸分泌的抑制作用

消旋（１５Ｒ）１５甲基ＰＧＥ２甲酯（ＰＧ６Ｅ）对在体大鼠胃酸分泌的抑制作用徐瑞明张守仁金碧燕韩超吴元鎏（中国医学科学院，中国协和医科大学药物研究所，北京１０００５０）ＰＧ６Ｅ是我所已合成的ＰＧＥ２类化合物，前文报道ＰＧ６Ｅ对动物实验性溃疡的保护作用...     

松果腺褪黑素对大鼠腹腔巨噬细胞化学发光和脾,下丘脑PGE2含量…

采用松果腺切除术、母多糖调理的鲁米诺依赖的化学发光法及前列腺素Ｅ２（ＰＧＥ２）放射免疫测定方法观察了松果腺和褪黑素（ＭＴ）对大鼠腹腔巨噬细胞化学发光及脾、下丘脑ＰＧＥ２含量的影响。结果表明：松果腺切除后大鼠腹腔巨噬细胞化学发光值降低，脾及下丘脑ＰＧＥ２含量升高，１０－１０００μｇ．ｋｇ＾－１ＭＴ分别恢复之。其中以１０μｇ．ｋｇ＾－１ＭＴ作用最强；１０μｇ．ｋｇ＾－１ＭＴ还抑制正常大鼠脾及下丘脑ＰＧ     

Effects of recombinant humanen dothelial-derived interleukin-8 on hemorhagic shock in rats

目的：研究重组人内皮细胞衍生的白细胞介素－８（ＩＬ８）对失血性休克的作用．方法：大鼠股动脉放血至ＭＡＢＰ５３２ｋＰａ，维持９０ｍｉｎ，复制晚期失血性休克模型．输血后，静脉注射ＩＬ８２５０μｇ·ｋｇ－１．放免法测定血浆ＥＴ１和６ＫＰＧＦ１α含量．结果：给予ＩＬ８后，ＭＡＢＰ显著提高，休克状态改善，２ｈ存活率相应提高；休克晚期血浆ＥＴ１水平比正常明显升高（２１±４ｖｓ８２±１８ｎｇ·Ｌ－１，Ｐ＜００１），血浆６ＫＰＧＦ１α含量明显降低（１０７±１２ｖｓ１５７±１１ｎｇ·Ｌ－１，Ｐ＜００１）．ＩＬ８显著降低血浆ＥＴ１水平（１０±４ｎｇ·Ｌ－１，Ｐ＜００１），提高血浆６ＫＰＧＦ１α含量（３６８±１６ｎｇ·Ｌ－１，Ｐ＜００１）．结论：ＩＬ８具有较好的抗休克作用．     

2－［对－（二甲氨基）苯乙烯］氯化甲基吡啶对大鼠心电图、豚鼠左心房收缩及乳头肌动作电位的影响

２－［对－（二甲氨基）苯乙烯］氯化甲基吡啶（ＤＳＰＭ－ＣＩ），是由氯取代２－［对－（二甲氨基）苯乙烯］碘化甲基吡啶（ＤＳＰＭ）上的碘而得。本文应用心电图、机械收缩描记方法及细胞内标准微电极技术，研究ＤＳＰＭ－Ｃｌ对大鼠心电图（ＥＣＧ）、豚鼠心房肌量效曲线及对豚鼠乳头肌快反应动作电位（ＡＰ）、高钾除极慢反应动作电位（ＳＡＰ）的影响。结果显示，ＤＳＰＭ－Ｃｌ（２ｍｇ·ｋｇ￣（－１））对大鼠有明显的负性频率、负性传导作用，分别使ＰＰ间期、ＰＲ间期延长达６６．２％（Ｐ＜０．０１），１７．０％（Ｐ＜０．０１），５０μｍｏｌ·Ｌ￣（－１）能明显抑制左心房收缩力，非竟争性拮抗Ｉｓｏ及ＣａＣｌ＿２对豚鼠左心房的正性肌力作用，ＰＤ￣２＇分别为４．６，４，３４，１００μｍｏｌ·Ｌ￣（－１）ＤＳＰＭ－Ｃｌ延长动作电位时程ＡＰＤ＿（９０），有效不应期（ＥＲＰ），降低高钾除极豚鼠乳头肌０期最大上升速率Ｖｍａｘ，其作用与Ｖｅｒ相似，提示ＤＳＰＭ－Ｃｌ可能为钙拮抗剂。     

Optimised synthesis of the 15N‐labelled insecticide phosmet (1)

A simple strategy for the small‐scale synthesis of the ¹⁵N‐labelled insecticide phosmet has been developed, starting from ¹⁵N‐phthalimide‐K. Copyright © 2004 John Wiley & Sons, Ltd.     

复方氨基酸(15)双肽(2)注射液临床用药调查研究

目的 通过研究全院外科病房复方氨基酸(15)双肽(2)注射液的应用现状,为进一步规范临床合理用药提供参考。方法 收集2012年7月外科病房使用复方氨基酸(15)双肽(2)注射液的患者127人的病历资料,统计其使用方法、使用疗程、使用时机、联合用药,以及各个科室之间的差别。结果 复方氨基酸(15)双肽(2)注射液外科病房使用存在的问题有:疗程过长(>14 d),比例占6.3%;外周途径给药,比例占62.2%;此外还有7.1%的患者是单独输注该药。结论 复方氨基酸(15)双肽(2)注射液在输注方式、疗程和联合使用其他肠外营养方面存在超说明书使用的现象,需要进一步规范,促进临床更加合理使用氨基酸类营养药物。     

Effect of 15-lipoxygenase metabolites, 15-(S)-HPETE and 15-(S)-HETE on chronic myelogenous leukemia cell line K-562: reactive oxygen species (ROS) mediate caspase-dependent apoptosis

Growth inhibitory effects of 15-lipoxygenase-1 [13-(S)-HPODE and 13-(S)-HODE] and 15-lipoxygenase-2 [15-(S)-HPETE and 15-(S)-HETE] (15-LOX-1 and LOX-2) metabolites and the underlying mechanisms were studied on chronic myeloid leukemia cell line (K-562). The hydroperoxy metabolites, 15-(S)-HPETE and 13-(S)-HPODE rapidly inhibited the growth of K-562 cells by 3h with IC(50) values, 10 and 15microM, respectively. In contrast, the hydroxy metabolite of 15-LOX-2, 15-(S)-HETE, showed 50% inhibition only at 40microM by 6h and 13-(S)-HODE, hydroxy metabolite of 15-LOX-1, showed no significant effect up to 160microM. The cells exposed to 10microM of 15-(S)-HPETE and 40microM of 15-(S)-HETE showed typical apoptotic features like release of cytochrome c, caspase-3 activation and PARP-1 (poly(ADP) ribose polymerase-1) cleavage. A flow cytometry based DCFH-DA analysis and inhibitory studies with DPI, a pharmacological inhibitor of NADPH oxidase, NAC (N-acetyl cysteine) and GSH revealed that NADPH oxidase-mediated generation of ROS is responsible for caspase-3 activation and subsequent induction of apoptosis in the K-562 cell line.     

在大鼠中15-LO/15-HETE参与缺氧对K_V1.5表达的抑制作用

目的采用分子生物学技术从组织和细胞水平上观察阻断15-LO/15-HETE后,缺氧对KV1.5表达的影响。方法通过酶法分离、培养Wistar大鼠肺动脉血管平滑肌细胞(pulmonary artery smooth muscle cells,PASMCs)和大鼠肺动脉,应用Western blot和RT-PCR方法分别从蛋白质水平和mRNA水平上观察在15-LO阻断剂CDC和NDGA作用下,缺氧对KV1.5表达的影响。结果从组织和细胞水平上,用CDC和NDGA阻断15-LO即阻断了内源性15-HETE的产生,KV1.5的表达量在蛋白质水平和mRNA水平与未阻断组比较都增加。在阻断了内源性15-HETE的产生以后,加入外源性15-HETE,KV1.5的表达量减低。说明不仅内源性15-HETE参与诱导缺氧对KV1.5表达的影响,外源性15-HETE也同样能影响缺氧条件下KV1.5的表达量。但在阻断了内源性15-HETE的产生以后,加入外源性15-HETE,KV1.5的表达量减低。说明不仅内源性15-HETE参与诱导缺氧对KV1.5表达的影响,外源性15-HETE也同样能影响缺氧条件下KV1.5的表达量。结论上述结果表明,从大鼠肺动脉组织和细胞水平上,内源性15-HETE介导了缺氧对KV1.5表达的抑制作用。     

Ethanol self-administration in freely feeding and drinking rats: effects of Ro15-4513 alone,and in combination with Ro15-1788 (flumazenil)

Recent work in our laboratory demonstrated that Ro15-4513, a partial inverse benzodiazepine (BDZ) agonist, decreases ethanol (ETOH) self-administration in rodents under fluid deprivation conditions. The present study further examined the effects of Ro15-4513 (2.5 and 5.0 mg/kg) alone and in combination with Ro15-1788, (flumazenil) (8.0 and 16.0 mg/kg), a BDZ receptor antagonist on ETOH self-administration in freely feeding and drinking rats. Animals were trained to consume ETOH (11% v/v) using a limited access procedure. Measurements were taken at 10- and 60-min intervals. Ro15-4513 (2.5 and 5.0 mg/kg) markedly attenuated ETOH consumption at both intervals. The antagonistic actions of Ro15-4513 were completely blocked by the higher dose of flumazenil at both intervals; the lower dose failed to antagonize the Ro15-4513-induced reduction of ETOH intake. When flumazenil was given alone, both doses reduced ETOH self-administration at 60 min; although the magnitude of the antagonism was comparable to that of Ro15-4513 only with the highest does of flumazenil (16.0 mg/kg). Neither Ro15-4513 nor flumazenil alone or in combination significantly altered water intake at any of the tested doses. Rats pretreated with Ro15-4513 showed a substantial reduction in blood ethanol concentration (BEC) compared with the Tween-80 vehicle condition at the 10-min interval. However, the BEC of animals given Ro15-4513 in combination with flumazenil were similar to rats given Tween-80 vehicle. The present study extends our previous research by demonstrating that Ro15-4513 and flumazenil attenuate ETOH self-administration in non-food or water deprived rats. These studies suggest that the suppressant effects of Ro15-4513 and flumazenil on ETOH self-administration are associated with actions at the BDZ site of the GABA_A receptor complex. These data are discussed in relation to the possible mechanism(s) by which Ro-15-4513 and flumazenil exert their antagonism on ETOH self-administration.Portions of this work were presented at the Annual Meeting of the Research Society on Alcoholism under the symposium entitled GABA/BDZ Receptor Update, Marco Island, FL, June 10, 1991.We would like to dedicate this paper to the late Dr. Richard G. Lister, a friend, teacher, colleague and exceptional scientist who contributed substantially to the area of alcohol abuse and alcoholism. Over the past years, Dr. Lister investigated the interactions of alcohol with inverse benzodiazepine agonists and benzodiazepine receptor antagonists. His seminal and more recent papers played an important role in delineating the GABA benzodiazepine systems in the neurobehavioral actions of alcohol. Richard, we will miss you.     

Interactions of Ro15-4513, Ro15-1788 (flumazenil) and ethanol on measures of exploration and locomotion in rats

The present study investigated the role of the GABA_A-benzodiazepine (BDZ) receptor complex in mediating ethanol (ETOH)-induced increases in exploration (head-dipping) and locomotion of rats in a holeboard test. Male Sprague-Dawley rats were selected based on low basal exploratory rates to increase the likelihood that ETOH would increase these behaviors. The effects of the BDZ partial inverse agonist, Ro15-4513 (2.5 mg/kg), and the BDZ receptor antagonist, Ro15-1788 (flumazenil) (8.0 mg/kg), alone, and in combination with ETOH (0.25, 0.50 and 0.75 g/kg, IP) were investigated. The 0.25 and 0.50 g/kg doses of ETOH markedly increased both exploration and locomotion in low exploratory rats. The ETOH-induced increases were prevented by Ro15-4513 on both measures at a dose that produced no observable intrinsic action; however, this apparent lack of intrinsic activity on exploration may have been related to the low basal rates of responding in the subjects. The BDZ antagonist, flumazenil, completely reversed the antagonistic action produced by Ro15-4513 of the ETOH-induced stimulant effects on locomotion, however, flumazenil exerted only a marginal statistically significant effect on Ro15-4513's actions on head-dipping. When flumazenil was given alone, it increased head-dipping, but was without effect on locomotion. Flumazenil did not affect ETOH-induced increases in locomotion; however, ETOH and flumazenil appeared to show agonistic effects on exlporation. The different effects exerted by flumazenil alone, and in combination with ETOH on head-dipping and locomotion suggest that the actions of flumazenil on these behaviors are mediated through separate mechanisms. The research further suggests that both the anxiolytic and locomotor activational effects of ETOH are mediated through the GABA_A-BDZ receptor complex.I would like to dedicate this paper to the late Dr. Richard G. Lister, a friend, teacher, colleague and exceptional scientist who contributed substantially to the area of alcohol abuse and alcoholism. Over the past years, Dr. Lister investigated the interaction of alcohol with benzodiazepine inverse agonists and benzodiazepine receptor antagonists. His seminal and more recent papers played an important role delineating the neuromechanisms of alcohol in relation to the GABA-benzodiazepine receptor complex. Richard, we will miss you.     

高效液相色谱法测定复方氨基酸(15)双肽(2)注射液中2种杂质的含量测定

目的:建立同时测定复方氨基酸(15)双肽(2)注射液中焦谷氨酸和环(甘氨酰-谷氨酰胺)含量的HPLC方法。方法:使用Aglient ZORBAX SB-C18色谱柱(250 mm×4.6 mm,5μm),流动相为0.01 mol.L-1磷酸氢二铵溶液(用磷酸调节pH至1.6),流速为1.0 mL.min-1;紫外检测波长为205 nm;柱温为15℃;进样量为50μL。结果:焦谷氨酸和环(甘氨酰-谷氨酰胺)浓度分别在25.15~503.0 mg.L-1和40.1~802.0 mg.L-1范围内线性关系良好,最低检测限(S/N=3)分别为75.45 ng和40.1 ng,平均回收率分别为100.9%和100.8%。结论:本方法用于复方氨基酸注射液中焦谷氨酸和环(甘氨酰-谷氨酰胺)含量的快速分析,方法简便、准确。