小剂量乙酰半胱氨酸治疗慢性肝损伤作用及其机制

目的 研究小剂量乙酰半胱氨酸（N-acetylcysteine,NAC）对CCl₄所致慢性肝损伤的疗效及其作用机制。方法 将大鼠分为正常对照组、模型组、小剂量NAC低、中、高剂量组和阳性对照组。小剂量NAC低、中、高剂量组分别给予45,90,180 mg·kg^-1,阳性对照组给予阿拓莫兰54 mg·kg^-1,正常对照组和模型组腹腔注射等容积灭菌生理盐水。采用CCl₄复制大鼠慢性肝损伤模型,末次给药后24 h麻醉大鼠,腹主动脉取血,检测血清ALT、AST含量以及肝组织中SOD、MDA、GSH和Hyp含量,观察肝脏组织病理学变化,免疫组化检测肝组织Nrf2、HO-1的表达。结果 与正常组比较,模型组大鼠血清ALT、AST、MDA和Hyp含量明显升高（P<0.01）,SOD、GSH虽有下降趋势,但结果无统计学差异,Nrf2、HO-1蛋白表达均增加,但差异无统计学意义。与模型组比较,小剂量NAC低、中、高剂量组ALT、AST水平明显降低（P<0.01）,低、中剂量组SOD、GSH、Hyp含量差异均有显著性（P<0.01或P<0.05）,高剂量组GSH、Hyp含量差异均有显著性（P<0.01或P<0.05）,各剂量组MDA均有下降趋势,但无统计学意义,低、中、高剂量组Nrf2、HO-1蛋白表达均增加,其中低剂量组差异有统计学意义（P<0.01或P<0.05）。结论 小剂量乙酰半胱氨酸对CCl₄诱导大鼠慢性肝损伤具有较好的治疗作用,其作用机制可能通过Nrf2/HO-1通路发挥抗氧化应激作用。     

瞿麦汤调控Nrf2/ARE信号通路对肾草酸钙结石大鼠氧化应激损伤作用机制研究

目的 研究敦煌医方瞿麦汤对肾草酸钙结石模型鼠核因子E2相关因子2（nuclear factor erythroid-2 related factor 2,Nrf2）/抗氧化反应原件（antioxidant response element,ARE）信号通路的影响,探讨其机制。方法 60只SD大鼠随机分为空白对照组、模型组、肾石通颗粒（5 g·kg^-1）组和敦煌医方瞿麦汤高、中、低剂量（20,10,5 g·kg^-1）组。除空白对照组外,其余各组大鼠采用1%乙二醇+2%氯化铵的溶液联合灌胃法制备大鼠肾草酸钙结石模型,同时给予相应药物,连续28 d。末次给药结束后,检测各组大鼠的体质量、肾指数,检测大鼠血清中SOD活性、MDA含量、T-AOC含量,HE染色法观察各组大鼠肾组织的病理形态学变化,RT-PCR法检测肾组织Nrf2 mRNA和NQO1 mRNA的表达,免疫组化法检测肾组织Nrf2和ARE的蛋白表达。结果 与空白对照组比较,模型组大鼠肾指数和MDA的含量均增加（P<0.05）,其体质量、SOD活性、T-AOC含量、Nrf2的基因表达和蛋白表达均下降,NQO1的基因表达下降（P<0.05）,ARE的蛋白表达下降（P<0.05）;与模型组比较,敦煌医方瞿麦汤各剂量组肾指数下降（P<0.05）,其体质量升高（P<0.05）;敦煌医方瞿麦汤中、高剂量组MDA含量下降（P<0.05）,Nrf2 mRNA和NQO1 mRNA的表达均升高（P<0.05）,Nrf2和ARE的蛋白表达均升高（P<0.05）;高剂量组T-AOC含量升高（P<0.05）。结论 肾草酸钙结石模型鼠存在氧化应激损伤,敦煌医方瞿麦汤可通过上调Nrf2/ARE信号通路相关因子表达抑制肾结石的形成来发挥治疗作用。     

当归茎叶与根对小鼠溶血性贫血模型的影响

目的 探讨当归茎叶与根对溶血性贫血小鼠的干预作用。方法 将90只小鼠随机分为9组：空白组,模型组,阳性组,当归茎叶水煎液组（高、中、低剂量）,当归根水煎液组（高、中、低剂量）,每组10只,♀♂各半。采用乙酰苯肼（acetyl phenyl hydrazine,APH）制造溶血性贫血模型（1,4,7 d皮下注射含有APH的生理盐水,APH剂量为0.2,0.1,0.1 g·kg^-1）,造模第1天给予当归根水煎液与茎叶水煎液灌胃治疗（0.02 mL·g^-1）,13 d后取样,检测其血常规（Hb、RBC、PLT）、脏器指数（脾、胸腺指数）、生化指标（G₆PD、GR、IL-2和EPO）以及观察肝、脾病理切片（苏木精-伊红染色）。结果 与模型组比较,当归茎叶水煎液与当归根水煎液均能显著升高Hb、RBC、PLT,降低脾指数,提高胸腺指数,升高小鼠血液中G₆PD、GR、IL-2、EPO的含量（P<0.05或<0.01）。另外,病理切片结果显示,当归茎叶水煎液和当归根水煎液均可减轻APH所致小鼠肝脏、脾脏细胞的点状坏死及瘀血。结论 当归茎叶水煎液与当归根水煎液对溶血性贫血小鼠均具有一定的改善作用。     

不同工艺紫雪散抗惊厥药效特点及机制研究

目的 研究普通工艺、传统工艺制备紫雪散的抗惊厥作用,初步探讨其作用机制。方法 采用雄性SPF级ICR小鼠,随机分为对照组,模型组,传统工艺紫雪散和普通工艺紫雪散低、中、高剂量（0.78、1.56、3.12 g·kg^-1）组及5%苯巴比妥（0.01 mL·g^-1）组。通过颈背部sc尼可刹米注射液诱发小鼠惊厥模型,观察各组小鼠治疗后的惊厥潜伏期、死亡潜伏期、20 min死亡率;采用比色法检测大脑皮层中钙水平;Griess reagent法检测大脑皮层总NO含量;参照试剂盒说明书检测大脑皮层中谷氨酸（Glu）、γ-氨基丁酸（GABA）含量。结果 与模型组比较,苯巴比妥钠、普通和传统工艺紫雪散的中、高剂量均可显著延长小鼠的惊厥潜伏期（P<0.001）;普通和传统工艺紫雪散的低、中、高剂量均可显著延长惊厥小鼠的死亡潜伏期（P<0.01、0.001）;模型组小鼠死亡率为100%,苯巴比妥钠组没有小鼠死亡,普通和传统工艺紫雪散的中、高剂量组死亡率明显降低。2种工艺紫雪散的抗惊厥作用具有剂量相关性,与普通工艺高剂量比较,传统工艺紫雪散高剂量可以显著延长惊厥模型小鼠的惊厥、死亡潜伏期（P<0.05、0.01）,降低惊厥致死率。与模型组比较,3.12 g·kg^-1传统工艺和普通工艺紫雪散、苯巴比妥钠均可以显著降低小鼠脑内钙含量（P<0.05、0.001）和总NO含量（P<0.001）;与普通工艺紫雪散组比较,3.12 g·kg^-1传统工艺紫雪散可以显著降低惊厥小鼠脑内总NO的含量（P<0.01）。与模型组比较,传统工艺和普通工艺紫雪散3.12 g·kg^-1组、苯巴比妥钠组小鼠脑皮层中Glu含量显著减少（P<0.05、0.001）;传统工艺紫雪散3.12 g·kg^-1组小鼠脑皮层中GABA含量显著增加（P<0.05）。结论 传统工艺和普通工艺紫雪散均具有抗惊厥作用,并且传统工艺紫雪散的抗惊厥作用优于普通工艺紫雪散。     

注射用丹参多酚酸对MCAO/R大鼠Nrf2/Keap1/HO-1信号通路的影响

目的 采用大鼠大脑中动脉栓塞/再灌注（MCAO/R）模型考察注射用丹参多酚酸（SAFI）对脑缺血再灌注大鼠核因子E2相关因子2（Nrf2）/Kelch样ECH相关蛋白（Keap1）/血红素氧合酶-1（HO-1）信号通路的影响。方法 线栓法构建大鼠MCAO/R模型,于术后24 h进行神经功能评分,将造模成功的大鼠随机分为模型组、丁苯酞（5 mL·kg^-1）组和SAFI低、中、高剂量（5.76、11.51、23.02 mg·kg^-1）组,尾iv给药,连续14 d。考察给药后各组大鼠神经功能缺损评分;ELISA法检测血清超氧化物歧化酶（SOD）、丙二醛（MDA）、脑源性神经营养因子（BDNF）水平;TTC染色法检测脑梗死体积;HE染色观察脑组织病理变化;Western blotting法检测Nrf2、Keap1、HO-1蛋白表达。结果 与模型组比较,SAFI中、高剂量组和丁苯酞组大鼠的神经功能缺损评分显著降低（P＜0.05、0.01） ;SAFI各剂量组和丁苯酞组脑梗死体积显著减少（P＜0.01、0.001）,血清BDNF、SOD水平均显著升高（P＜0.05、0.01、0.001）,MDA水平显著降低（P＜0.05、0.01）,脑组织病理变化明显减轻,水肿减轻; SAFI高、中剂量组及丁苯酞组Keap1、Nrf2、HO-1蛋白表达显著升高（P＜0.05、0.01、0.001）,SAFI低剂量组Keap1、HO-1蛋白表达显著升高（P＜0.01、0.001）。结论 SAFI可以减轻大鼠脑缺血再灌注损伤,可能是通过促进Nrf2/Keap1/HO-1信号通路,抑制氧化损伤实现的。     

葡萄籽原花青素对酒精性肝损伤小鼠的保护作用

目的 考察葡萄籽原花青素（grape seed procyanidin,GSP）对酒精性肝损伤小鼠的保护作用及其抗炎机制。方法 ICR小鼠60只,♂,随机分成正常对照组、模型组（56%乙醇）、水飞蓟素组（56%乙醇+90 mg·kg^-1·d^-1水飞蓟素）及GSP高、中、低剂量组（56%乙醇+400,200,100 mg·kg^-1·d^-1GSP）。8周后用分光光度法检测血清中ALT、AST水平,肝MDA含量和SOD、GSH-Px活力;酶联免疫法检测肝NF-κB、TNF-α、IL-1β的含量;HE染色检测肝脏病理改变。结果 与模型组比较,GSP可以降低酒精性肝损伤小鼠血清中ALT、AST含量及肝组织中MDA、NF-κB、TNF-α、IL-1β含量（P<0.05）,提高SOD、GSH-PX活力（P<0.05）,减轻肝脏的病理损伤程度（P<0.05）。结论 GSP对酒精性肝损伤小鼠具有保护作用,其机制可能是通过抗氧化和降炎症反应来发挥作用。     

姜黄素对四氯化碳诱导大鼠急性肝损害的保护作用

目的 研究姜黄素对四氯化碳诱导的大鼠急性肝损伤的保护作用及其机制。方法 60只健康♂SD大鼠随机分成6组,即正常对照组,肝损伤模型组,阳性药物对照水飞蓟素组（100 mg·kg^-1）,姜黄素低剂量组（25 mg·kg^-1）,姜黄素中剂量组（50 mg·kg^-1）和姜黄素高剂量组（100 mg·kg^-1）。隔天灌胃给药,共30 d;末次给药1 h后,腹腔注射20 mg·kg^-1 CCl₄玉米油溶液（2 mL·kg^-1）造模,禁食不禁水,12 h后乌拉坦麻醉。取下腔静脉血和肝脏后,分别检测大鼠血清中丙氨酸氨基转移酶（AST）及天门冬氨酸氨基转移酶（ASL）的活性,大鼠肝脏组织中血红素加氧酶Ⅰ（HO-1）及静脉血中HbCO的水平,在体外测定姜黄素清除DPPH自由基及ABTS自由基的能力。结果 与正常对照组相比,模型组血清中ALT、AST活性显著升高,肝组织中HO-1活性及静脉血中HbCO的含量显著降低,组织病理检查显示肝组织损伤明显增加。与模型组相比,姜黄素各剂量组可不同程度的降低血清AST及ASL的活性,增加肝脏组织中HO-1的活性及HbCO的水平,组织病理检查显示肝损伤有不同程度减轻。并且姜黄素具有清除DPPH自由基及ABTS自由基的能力。结论 姜黄素对CCl₄诱导的大鼠急性肝损伤具有一定保护作用,其机制可能与其自身抗氧化能力及诱导HO-1及HbCO有关。     

丙酮酸乙酯对利福平致小鼠肝损伤的保护作用

目的 探讨丙酮酸乙酯（EP）对利福平致小鼠肝损伤的保护作用及其可能机制。方法 24只C57BL/6小鼠随机分成3组：正常对照组、模型组（利福平,200 mg·kg^-1·d^-1） 和EP组（利福平200 mg·kg^-1·d^-1+丙酮酸乙酯40 mg·kg^-1·d^-1）,每组8只。造模后第7天处死小鼠,检测小鼠血清谷丙转氨酶（ALT）、总胆红素（TBIL）、直接胆红素（DBIL）、碱性磷酸酶（ALP）,观察小鼠肝脏病理学变化,检测小鼠肝组织总胆汁酸（TBA）、丙二醛（MDA）的含量、超氧化物歧化酶（SOD）活性、高迁移率族蛋白B1 （HMGB1） 及乙酰化的HMGB1（AC-HMGB1）蛋白的表达情况。结果 与正常对照组相比,模型组小鼠血清TBIL、DBIL、ALP、ALT水平升高（P<0.05）;肝细胞空泡变性、脂肪变性明显,部分肝细胞可见嗜酸性变、核溶解或固缩;肝组织TBA、MDA的含量提高（P<0.05）,SOD减少（P<0.05）,HMGB1及AC-HMGB1表达增多（P<0.05）,HMGB1胞浆表达为主。与模型组相比,EP组小鼠血清TBIL、DBIL、ALP、ALT水平降低（P<0.05）;肝组织病理学变化改善;肝组织TBA、MDA的含量降低（P<0.05）, SOD增多（P<0.05）,HMGB1及AC-HMGB1的表达水平降低（P<0.05）,HMGB1以胞核表达为主。结论 丙酮酸乙酯能够减轻利福平所致的小鼠肝损伤,其机制可能与丙酮酸乙酯抗氧化,下调肝组织HMGB1及AC-HMGB1的表达和调节HMGB1的分布有关。     

固本明目颗粒对D-半乳糖性白内障模型大鼠抗氧化作用的研究

目的 研究固本明目颗粒1和固本明目颗粒2预防给药对D-半乳糖性白内障的抗氧化作用及固本明目颗粒工艺改变前后作用的差别。方法 取20日龄SD大鼠90只,雄性,试验随机分为9组,分别为空白对照组、模型对照组、阳性对照组、固本明目颗粒1和2 均设 1.25、2.5、5 g•kg^-1.BW三个剂量组,每组10只。采用D-半乳糖建立大鼠的糖性白内障模型,各剂量组灌胃给予相应剂量的药物溶液10 mL•kg^-1.BW,每天1次,连续21d,观察各组大鼠晶状体浑浊程度,末次给药后检测各组大鼠晶状体内SOD、GSH、GST、GSH-Px、Na+-K+-ATP酶活性情况,以及各组大鼠晶状体组织病理学改变。结果 与模型对照组比较,固本明目颗粒1低剂量组GSH、中剂量组SOD、高剂量组GST明显升高（P＜0.05）;固本明目颗粒2中、高剂量组GSH、中剂量组SOD明显升高（P＜0.05或P＜0.01）。阳性对照组、固本明目颗粒1各剂量组和固本明目颗粒2各剂量组晶状体混浊程度均有明显缓解效果。结论 固本明目颗粒1和固本明目颗粒2在1.25、2.5、5 g•kg-1.BW剂量下对D-半乳糖性白内障有一定的抗氧化作用,固本明目颗粒制备工艺改变前后抗氧化作用未见明显变化。     

土茯苓对环孢素A诱导的免疫抑制小鼠免疫功能的影响

目的 探讨土茯苓水提液对环孢素A诱导的免疫抑制小鼠免疫功能的影响。方法 小鼠腹腔注射环孢素A 5 d致免疫抑制模型,造模成功后随机分为模型组、左旋咪唑组（3.79 g·kg^-1,阳性药）和土茯苓低、中、高剂量组（4.55,9.1,13.65 g·kg^-1）（n=16）,连续给药治疗5 d后,处死小鼠,取脾、胸腺,称重计算脾指数和胸腺指数,流式细胞术检测CD3⁺CD4⁺,CD3⁺CD8⁺;酶联免疫吸附法检测IL-2,IL-6,IFN-γ。结果 造模后小鼠脾指数显著高于正常对照组（P<0.05）,胸腺指数明显降低,脾T细胞CD3⁺CD4⁺显著降低（P<0.05）;与模型组比较,各治疗组小鼠脾指数均有不同程度降低,土茯苓水提液中剂量组差异显著（P<0.05）,但胸腺指数无显著变化;左旋咪唑组、土茯苓中、高剂量组脾T细胞CD3⁺CD4⁺数目显著增加（P<0.01）,各治疗组脾脏IFN-γ均显著下降（P<0.05）。结论 土茯苓水提液能通过降低脾指数、增加脾T细胞CD3⁺CD4⁺的数目,增强机体免疫功能,并下调脾脏内较高的IFN-γ,其调节机制可能与左旋咪唑类似。     

Synthesis and evaluation of 2,6-piperidinedione derivatives as potentially novel compounds with analgesic and other CNS activities

New 2,6-piperidinediones 2_a–g and 4_a–d were prepared by initial condensation of aromatic aldehydes or cycloalkanones with cyanoacetamide to give α-cyanocinnamides l_a–g or cycloalkylidenes 3_a,b which underwent Michae1 addition with ethyl cyanoacetate or diethylmalonate. Compounds 4_a–d were alkylated by various alkyl halides to produce the N-alkylated 2,6-piperidinedione derivatives 5_a–m. Some new selected compounds 2_a–c,f, 4_a–d & 5_e,h,j were pharmacologically evaluated for potential anticonvulsant, sedative and analgesic activities. These compounds exhibited significant anticonvulsant and analgesic effects after a single I.P. administration 100 mg/kg b.wt. . On the other hand all the investigated compounds induced hypnotic activity and prolonged the phenobarbital sodium- induced sleep as compared with the control group and the most potent compound was found to be 2_f.     

鼻渊净胶囊的HPLC指纹图谱研究

目的 建立鼻渊净胶囊的高效液相色谱(HPLC)指纹图谱.方法 采用Agilent SB-C18(4.6 mm×250 mm,5μm)色谱柱,乙腈-水为流动相、以1.0 ml/min流速行梯度洗脱,检测波长210 nm,柱温30℃,洗脱时间为80 min.采用中药色谱指纹图谱相似度评价系统(2004A版)对检测出色谱进行...     

NEURAMIDE STIMULATES ADRENOCORTICOTROPIN BUT NOT PROLACTIN RELEASE FROM RAT PITUITARY

Neuramide (NMD), a substance found in crude preparations of porcine stomach extract, is a viral inhibitor that also has putative immunostimulatory effects. The effects of NMD on stress-hormone (ACTH and prolactin—PRL) release were assessed inin vivoandin vitrostudies. In the former, blood levels of corticosterone and PRL were measured in NMD-treated male rats.In vitroexperiments were performed to evaluate the effects of NMD and three of its fractions (obtained with high performance liquid chromatography) on ACTH and PRL release from perfused rat pituitary slices. NMD increased plasma corticosterone levelsin vivoand produced dose-dependent increases inin vitropituitary release of ACTH. No effects on PRL secretion were observedin vivoorin vitro. The stimulatory effects on ACTH release were caused by the NMD fraction with a molecular weight of >5000<10000Da.     

EFFECT OF POLICOSANOL SUCCESSIVE DOSE INCREASES ON PLATELET AGGREGATION IN HEALTHY VOLUNTEERS

Policosanol is a cholesterol-lowering drug with hypocholesterolemic effects demonstrated in experimental models, healthy volunteers and type II hypercholesterolemic patients. In addition, antiplatelet effects of policosanol have been shown in experimental models and healthy volunteers. The effect of successively increasing doses of policosanol on platelet aggregation was investigated in a randomized, placebo-controlled, double-blind study conducted in 37 healthy volunteers. The volunteers were on a placebo-baseline period (two tablets per day) for 7 days and thereafter they received randomly, under double-blind conditions, placebo or policosanol (10mgday⁻¹) for 7 days. After this period dosage was doubled to 20mgday⁻¹for the next 7 days and then again doubled to 40mgday⁻¹, while the control group received placebo tablets all the time. Platelet aggregation as well as coagulation time was measured at baseline and after each dosing step. Results showed that antiplatelet effects of policosanol were successfully enhanced throughout the study, thus suggesting a dose-dependent relationship. No significant effect was reached during the first dosing period, but significant reductions of epinephrine and ADP-induced platelet aggregation were observed after the second one. Finally, a significant inhibition of platelet aggregation induced by all the agonists was observed at the last dosing step. Coagulation time remained unchanged during the trial.     

Investigation of the prevalence of tetQ, tetX and tetX1 genes in Bacteroides strains with elevated tigecycline minimum inhibitory concentrations

In this study, the antibiotic susceptibilities to tigecycline and tetracycline of 35 selected Bacteroides fragilis group strains were determined by Etest, and the presence of tetQ, tetX, tetX1 and ermF genes was investigated by polymerase chain reaction (PCR). tetQ was detected in all 12 B. fragilis group isolates (100%) exhibiting elevated tigecycline minimum inhibitory concentrations (MICs) (≥8 μg/mL) as well as the 8 strains (100%) with a tigecycline MIC of 4 μg/mL, whilst tetX and tetX1 were present in 15% and 75% of these strains, respectively. All of these strains were fully resistant to tetracycline (MIC ≥ 16 μg/mL). On the other hand, amongst the group of strains with tigecycline MICs < 4 μg/mL (15 isolates), tetQ, tetX and tetX1 were found less frequently (73.3%, 13.3% and 46.7%, respectively). All but two strains harbouring the tetQ gene in this group were non-susceptible to tetracycline, with a MIC > 4 μg/mL. These data suggest that in most cases tigecycline overcomes the tetracycline resistance mechanisms frequently observed in Bacteroides strains. However, the presence of tetX and tetX1 genes in some of the strains exhibiting elevated MICs for tigecycline draws attention to the possible development and spread of resistance to this antibiotic agent amongst Bacteroides strains. The common occurrence of ermF, tetX, tetX1 and tetQ genes together predicted the presence of the CTnDOT-like Bacteroides conjugative transposon in this collection of Bacteroides strains.     

INDIRECT PARASYMPATHOMIMETIC ACTIVITY OF THE CLASS III ANTIARRHYTHMIC SUBSTANCE / -SOTALOLIN VITRO: REVERSIBLE INHIBITION OF CHOLINESTERASE ISOENZYMES FROM BLOOD AND THE HUMAN CENTRAL NERVOUS SYSTEM

Inhibitory effects of the class III antiarrhythmic compound / -sotalol on acetylcholinesterase (AChE; EC 3.1.1.7) isoenzymes of both erythrocytes and the human caudate nucleus and on serum cholinesterase (ChE; EC 3.1.1.8) were studiedin vitrousing a spectrophotometric kinetic assay with acetylthiocholine (ASCh) as substrate. Sotalol concentrations in the assays varied from 0.32 to 3.2m . All isoenzymes studied were inhibited by / -sotalol in a reversible and concentration-dependent manner. Double reciprocal plots of the reaction velocity against varying ASCh concentrations revealed that / -sotalol reduced substrate affinity (apparent Michaelis constant, KM, increased) of serum ChE, but did not change the enzyme's maximal rate of ASCh hydrolysis (V_max). Thus, / -sotalol inhibition of serum ChE was of the competitive type (rate constant for reversible competitive inhibition: K_i=0.51m ). In contrast, / sotalol reduced the maximal reaction velocity of the AChE isoenzyme from the central nervous system (caudate nucleus), but had no influence on substrate affinity of the enzyme (K_Mwith ASCh unchanged) indicating purely non-competitive inhibition kinetics (rate constant of reversible non-competitive inhibition: K_i′=0.44m ). / -sotalol inhibition of erythrocyte AChE was of mixed competitive/non-competitive type (K_i=0.31m , K_i′=0.49m ). Non-competitive / -sotalol inhibition of caudate nucleus AChE and the non-competitive component of erythrocyte AChE inhibition cannot be overcome by increased concentrations of the cholinergic transmitter acetylcholine (ACh). Peak / -sotalol plasma levels as described in the literature for both humans (15μ ) and experimental animals (dogs: 18μ ; rats: 260μ ) as well as maximal myocardial concentrations of the substance (dogs: 46μ ; rats: 478μ ) are in the range of about 2% to 100% of the sotalol inhibition rate constants determined in the present paper for cholinesterase isoenzymesin vitro. Thus, / -sotalol inhibition of ACh hydrolysisin vivomay contribute to both the well known antiarrhythmic potential and proarrhythmic side effects of the compound.     

AMELIORIATION OF CHEMICALLY-INDUCED HEPATOCYTE INJURY BY CYCLOSPORINE A

Cyclosporine A, beside its current applications, possesses potential hepatoprotective effects. This study was directed to investigate the effect of Cyclosporine A pretreatment on hepatic injury due to carbon tetrachloride (CCl₄) and -galactosamine. Rats were injected by two successive doses of Cyclosporine A (5mgkg⁻¹day⁻¹). Six hours after the second dose, 1mlkg⁻¹of CCl₄was administered i.p. Effects associated with Cyclosporine A pretreatment were examined by using isolated hepatocytes and hepatocytes that were immobilized and continuously perfused. -Galactosamine (5m ) was added directly to the perfusion medium. After isolation, hepatocytes were examined histologically by light and electron microscopy, immobilized and perfused for further metabolic functional activity evaluation. Cyclosporine A pretreatmentin vivoproduced hepatoameliorative effects of various degrees which were statistically significant as manifested by: (1) an increased trypan blue exclusion after CCl₄; (2) an improved ureagenesis after CCl₄; (3) a reduction in the lipid droplets accumulation in the cytoplasm produced by CCl₄administration; (4) well preserved cytoplasmic organelles as mitochondria, endoplasmic reticulum ER, nuclear chromatin structures that were altered by CCl₄; and (5) an increased hepatocytes survival in the agarose gel matrix, reduction of LD leakage and improvement of ureagenesis after -galactosamine addition to the perfusion medium. The beneficial effect of Cyclosporine A pretreatment in modifying hepatotoxicity of chemical insults merits further studies.     

喙果黑面神化学成分研究

目的研究大戟科植物喙果黑面神(Breynia rostrata Merr.)的化学成分。方法利用硅胶、凝胶等色谱技术分离纯化化学成分,根据化合物的理化性质和光谱数据进行结构鉴定。结果从喙果黑面神的正丁醇萃取部分分离得到4个化合物,分别鉴定为6-O-甲基丙酰基-α-D-吡喃葡糖(6-O-methylpropanoyl-α-D-glucopyranose,1);4″-苯酚基-6-O-甲基丙酰基-β-D-吡喃葡糖苷(4″-phenolic-6-O-methylpropanoyl-β-D-glucopyranoside,2);1-O-没食子酰基-β-D-吡喃葡糖苷(1-O-galloyl-β-D-glucopyranoside,3);熊果苷(arbutin,4)。结论化合物1和2为新化合物,3和4均为首次从该种植物分离得到。     

EFFECTS OF 2-GUANIDINE-4-METHYLQUINAZOLINE ON GASTRIC ACID SECRETION IN RATS

In this study 2-guanidine-4-methylquinazoline (2-GMQ) appeared to decrease basal and stimulated gastric acid secretion, while structurally related compounds as dimethyl- biguanide, cyanoguanidine and 2-cyanoamino-4-methylpyrymidine did not. Thus, there is an antisecretory effect when the biguanide group is associated with a lipophilic structure. The antisecretive effects exerted by 2-GMQ are associated with anti H₂-histamine activity.The anti H₂-histamine nature of the effects of 2-GMQ was confirmed by the capacity of this compound of depressing the chronotropic activity of the isolated guinea pig auricle increased by histamine, as well as relaxant activity in rat uterus contracted by histamine, since both preparations are rich in H₂-histamine receptors.     

栝楼不同药用部位质量控制的研究进展

瓜蒌子、瓜蒌皮、瓜蒌、天花粉来源于栝楼的不同药用部位,4味药材均为常用的大宗药材,现行版《中国药典》对其制定的质量标准过于简单,无法科学合理地控制其质量。本文对瓜蒌子、瓜蒌皮、瓜蒌、天花粉安全性和有效组分的研究进行综述,明确了相关研究存在的问题并针对问题提出建议,为科学全面的药材及饮片标准的制定提供参考依据。