鹿茸多胺对小鼠肝细胞RNA聚合酶活性的影响

多次给小鼠po鹿茸多胺(PASPA)30mg/kg,可明显促进[³H]leucine和[³H]uridine掺入肝组织蛋白质和RNA。体外实验证明,鹿茸多胺在较低浓度(1～10μg/ml)时,对RNA聚合酶活性呈明显的增强作用。提示,鹿茸多胺刺激小鼠肝组织蛋白和RNA合成效应是由于其能够明显增强RNA聚合酶活性,尤其是显著增强RNA聚合酶Ⅱ的活性。     

鹿茸神经节甙酯对小鼠学习记忆功能的影响

多次皮下注射鹿茸神经节甙酯0.5g/kg对小鼠记忆获得、记忆再现、记忆巩固三个不同记忆阶段均有明显的促进作用;对[~3H]Leu-cine和[~3H]Uridine掺入小鼠脑组织蛋白和RNA有明显增加作用。此结果提示:鹿茸神经节甙酯促进学习记忆功能与小鼠脑内的蛋白质合成增加有密切关系。     

人参茎叶皂甙对正常和利血平化小鼠肝、肾组织的DNA,RNA及蛋白质合成的影响

本实验表明,人参茎叶皂甙(GSL)25mg/kg/日,连续灌胃给药7日,对小鼠肝肾组织 RNA 合成均有增加作用(p<0.01);GSL 25mg/kg,50mg/kg 对肝、肾组织蛋白合成亦均有增加作用(p<0.01和 p<0.05);GSL 25mg/kg,50mg/kg 对肝、肾组织 DNA 合成均无促进作用(p>0.05);GSL 对利血平化脾虚小鼠外观症状有轻度改善作用,除 GSL50mg/kg 对脾虚小鼠肝脏蛋白质合成有增加作用(p<0.05)外,其它与利血平对照组相比均无显著差异。     

从远志中分离鉴定出一种多巴胺受体活性化合物

从中药远志中提出一种多巴胺受体的配基,四氢非州防己胺。此化合物在体外可抑制[³H]SCH23390和[³H]螺哌隆与大鼠纹状体膜的结合,IC₅₀值分别为0.75±0.08μmol·L^-1和0.92±0.10μmol·L^-1。它在体外还能抑制[³H]哌唑嗪和大鼠脑皮质细胞膜结合(IC₅₀值为46μmol·L^-1),但不能改变[³H]QNB及[³H]muscimol对膜的结合。Scatchandplot分析显示此化合物对[³H]SCH23390和[³H]螺哌隆与膜结合的抑制作用是通过竞争性与非竞争性混合机制而实现的。     

月橘烯碱抗着床作用及其激素活性的研究

小鼠于妊娠第1～3天,po或sc月橘烯碱(yuehchukene)2mg或4mg/kg·d有明显的抗着床作用。金黄地鼠于妊娠1～3天,sc月橘烯碱4mg/kg·d却无此作用。月橘烯碱有明显的雌激素活性,与雌二醇合用有协同作用。该化合物无雄激素或抗雄激素活性;无孕激素或抗孕激素活性。放射受体竞争实验测得月橘烯碱对[³H]-雌二醇与雌激素受体特异性结合抑制50%的浓度(IC₅₀)为4.2×10^-6mol/L,表观解离常数(KI)为1.24×10^-6mol/L。说明月橘烯碱与雌激素受体有一定的亲和力。     

纳洛肼及14-羟基双氢吗啡肼与阿片受点结合的可逆性

用纳洛肼(NZI,1×10^-5M)或14-羟基双氢吗啡肼(HZI,1×10^-6)与大鼠脑匀浆P₂膜制备保温后,以Tris缓冲液反复洗涤,阿片受点可完全恢复与[³H]双氢吗啡([³H]DHM)的结合能力。在离体豚鼠回肠纵肌(GPI)试验中,HZI对电刺激收缩的抑制及NZI对吗啡(Mor)抑制作用的对抗亦皆可被洗掉,此外HZI对收缩的抑制还可被纳洛酮(Nal)所逆转,说明它们与阿片受点的结合都是可逆的。HZI镇痛作用ED₅₀为1.3 mg/kg(小鼠热板法SC),略强于Mor(3 mg/kg),持续时间与Mor相似。NZI对Mor镇痛的对抗可持续十余小时。     

间硝苯地平对血管紧张素Ⅱ促进血管平滑肌细胞增殖和蛋白质合成的影响

以培养血管平滑肌细胞(vascularsmcothmusclecell,VSMC)为模型,观察了间硝苯地平(m-nifedipine,m-Nif)对血管紧张素Ⅱ(angiotensinⅡ,ANGⅡ)促进VSMC增殖和蛋白质合成的影响。结果表明,m-Nif抑制ANGⅡ(100nmol·L^-1)引起VSMC[³H]thymidine和[³H]leucine参入,并呈剂量依赖性。m-Nif(2×10^-6mol·L^-1)可抑制ANGⅡ对VSMC的刺激、DNA及蛋白质合成速率,分别降低了46%,58%,53%。提示m-Nif可抑制ANGⅡ对VSMC增殖和蛋白合成的促进作用。     

黄花夹竹桃次甙乙的药代动力学研究

本文研究[³H]标记的黄花夹竹桃次甙乙(Neriifolin简称次甙乙)在大鼠体内的药代动力学。静脉注射后[³H]-次甙乙在血浆中的消除半衰期(T_1/2β)为5天,分布容积(Vd)为15.3L/kg。药物的主要分布在肝脏、胆汁和胃肠道内。灌胃给药吸收迅速完全,30 min血药浓度即达高峰。无论静脉注射或灌胃后,放射性主要从粪中排出,尿中较少,排出形式主要是代谢产物。[³H]-次甙乙与血浆蛋白的结合为91.7%。结果表明:次甙乙在大鼠体内的药代动力学特点与一般亲脂性强心甙相似。     

原代培养大鼠肝细胞中观察十种中药的抗肝毒作用

利用半乳糖胺GalN或四氯化碳CCI₄引起原代培养大鼠肝细胞损伤模型,研究10种中药水提液的抗肝毒作用。结果表明:丹参、田基黄、过路黄、野萄花2—50mg/ml;女贞子、车前子10—50mg/ml;山栀、垂盆草、海金沙及干姜50mg/ml可使含GaIN5x10^-3mol/L肝细胞培养液中GPT活性显著降低。其中丹参与田基黄又分别在CCI₄1.0x10^-2mol/L损伤肝细胞培养液及CGI₄实验性肝损伤小鼠中验证,均显示明显的护肝作用.     

n,n′-二乙酰-L-胱氨酸对半乳糖胺联用脂多糖引起小鼠免疫性肝衰竭的作用

目的研究n,n′-二乙酰-L-胱氨酸(DiNAC)对免疫性肝衰竭的治疗作用。方法观察DiNAC对Balb/C小鼠由半乳糖胺联用脂多糖引起免疫性肝衰竭的作用。半乳糖胺/脂多糖攻击6 h后，小鼠血清ALT，AST和外周血T细胞亚群分别用全自动生化仪、流式细胞仪测定，并用光镜观察肝组织病理切片，统计半乳糖胺/脂多糖攻击24 h后的小鼠存活率。结果给肝衰竭小鼠ip DiNAC(50，200，800 mg·kg^-1)，能明显阻止小鼠血清ALT和AST活力增高，使肝组织损害减轻及提高小鼠存活率，并呈剂量依赖关系；DiNAC能增强免疫性肝衰竭小鼠外周血CD4⁺,CD8⁺,Th1和Th2 T淋巴细胞的增殖分化。结论DiNAC对免疫性肝衰竭动物有明显的治疗作用，这一作用与其免疫调节有关。     

Effects of complex of 3,6-di-(dimethylamino)-dibenzopyriodonium with praseodymium dicitrate on the syntheses of DNA, RNA, protein, nucleoprotein and ATP of leukemia L 7712 cells in mice

The incorporations of [3H] thymidine, [3H]uridine and [3H]leucine into DNA, RNA and protein synthesis in leukemia 7712 cells were inhibited by the complex of 3,6-di-(dimethylamino)-dibenzopyriodonium with praseodymium (Pr, rare earth element) dicitrite 34 micrograms/ml for 3-24 h. The degree of inhibition increased in proportion to the incubation time. After being treated with [C17H20N2I]3[Pr(C6H5O7)2] 34 micrograms/ml for 3, 6, 12 and 24 h, the incorporation of [32P]Na2HPO4 into the nucleoprotein of leukemia 7712 cells was inhibited by 49, 57, 65 and 85%, while those into ATP were inhibited by 43, 59, 65 and 83%, respectively. The ID50 of [C17H20N2I]3[Pr(C6H5O7)2] on DNA synthesis in leukemia 7712 cells at 24 h was 22 micrograms/ml. After the complex was removed from the medium entirely, the rate of DNA synthesis decreased with time over 3-12 h. This result indicated that the inhibition mechanism was likely due to damage to the DNA template.     

Effects of T-2 toxin gavage on the synthesis and contents of rat-liver macromolecules

Effects of oral administration of T-2 toxin (0.75 mg/kg body weight/day) for 7, 14 or 21 days on the liver and plasma of young male rats were studied. A significant decrease in body weight and an increase in liver weight were observed in rats treated with T-2 toxin. Liver protein and glycogen levels were significantly lower than in controls after 21 days of treatment, but no significant differences were observed after 7 or 14 days. Levels of RNA in liver were significantly increased after 7, 14 and 21 days of treatment whereas liver DNA levels were significantly lower than in controls at each time interval. Liver microsomal protein was significantly decreased after 14 and 21 days, but microsomal RNA contents were significantly increased at 7 days and significantly decreased at 21 days. The levels of serum protein at 7, 14 and 21 days and of blood glucose at 14 and 21 days were significantly lower in T-2 toxin-treated rats. The levels of incorporation of [14C]leucine and [3H]uridine into liver protein and RNA, and into liver microsomal protein and RNA, were higher than in controls at 7 days, but then decreased. The incorporation of [3H]thymidine into liver DNA was not significantly altered in animals treated with the toxin.     

缓激肽B2受体拮抗剂艾替班特降低卡托普和对培养新生大鼠心肌细胞 …

AIM: To study whether endogenous kinins are negative modulators in the growth of cardiomyocytes and their possible cellular and molecular mechanisms. METHODS: Cultured neonatal rat cardiomyocytes were used. Intracellular RNA and protein synthesis were measured by [3H]uridine incorporation and [3H]leucine incorporation, respectively. The expression level of proto-oncogene c-myc, c-fos mRNA was observed by Northern blotting. RESULTS: Exposure of cardiomyocytes to captopril (Cap, 100 mumol.L-1) for 48 h inhibited the rates of [3H]Urd and [3H]Leu incorporations by 25% and 26%, respectively, and for 2 h inhibited c-myc, c-fos mRNA expression by 75% and 55%, respectively. Treatment of angiotensin II (Ang II, 1 mumol.L-1) for 48 h significantly increased the rates of [3H]Urd and [3H]Leu incorporations and for 1 h induced c-myc, c-fos mRNA overexpression, which were reduced by pretreatment with Cap (100 mumol.L-1). Icatibant acetate (Hoe 140, a specific antagonist of bradykinin B2 receptor) 0.1-10 mumol.L-1 blocked the effects of Cap in a concentration-dependent manner. CONCLUSION: Endogenous kinins exhibited a negative modulatory effect on growth of cardiomyoctes via BK B2 receptor.     

In vitro effect of aflatoxin B1 on rat liver macrophages (Kuffer cells)

The effect of aflatoxin B1 on the uptake and incorporation of [3H]leucine and [3H]uridine and on phagocytosis of latex particles was studied using cultures of rat liver macrophages (Kuffer cells). Aflatoxin B1 inhibited the incorporation of both isotopes, but inhibition of uridine incorporation was greater than that of leucine, suggesting that RNA synthesis was a major site of inhibition. Aflatoxin B1 also inhibited phagocytosis of latex particles in a time- and dose-dependent manner.     

Acetaldehyde inhibition of protein synthesis in isolated rat pancreatic acini

Exposure of isolated dispersed pancreatic acini to increasing concentrations of ethanol (5 to 500 mM) or acetaldehyde (0.5 to 100 mM) produced a progressive inhibition of [3H]leucine incorporation into both "cellular" (those remaining in the cell) and "secretory" (those released into the medium) proteins. Whereas 500 mM ethanol caused 90-95% inhibition in the synthesis of "cellular" and "secretory" proteins, the concentration of acetaldehyde needed to produce a similar inhibition was found to be 50 mM. All subsequent experiments were performed with 12.5 mM acetaldehyde, a concentration that consistently inhibited acinar protein synthesis by about 50%. The acetaldehyde-mediated inhibition of acinar protein synthesis was partially normalized when this metabolite was removed after 30 min during a 90-min incubation period. In the presence of acetaldehyde, the secretion of 3H-pulse-labeled proteins, but not amylase, trypsinogen, or chymotrypsinogen, was greatly depressed. Acetaldehyde also caused a marked reduction in [3H]uridine incorporation into acinar RNA. The entry of [3H]uridine, [3H]leucine, and [3H]aminoisobutyric acid into isolated acini was found to be slightly (15-25%) decreased by acetaldehyde. It is concluded that acetaldehyde exerts a direct toxic effect on isolated dispersed pancreatic acini as evidenced by diminution of both protein and RNA synthesis and decreased secretion of the newly synthesized proteins. This inhibitory effect of acetaldehyde could be partially reversed.     

Changes in protein and RNA synthesis in rat brain neurons after a single dose of methylmercury

Methylmercury was given to 30-day-old Wistar rats, At 1-7 days later the protein and RNA synthesis was studied in vivo by injecting a mixture [14C]leucine and [3H]uridine. Protein and RNA were precipitated from isolated cerebral and cerebellar neurons. The reduction of RNA synthesis coincides or precedes the reduced protein synthesis.     

Cortisol effect on protein synthesis and ribonucleic acid polymerase activity in rat thymus

The time course for cortisol to effect a decrease in the amount of soluble (extractable) thymic nuclear RNA polymerase activity was determined. Decreases in soluble polymerase activity were compared with the cortisol-mediated inhibition of [³H]leucine ([³H]leu) incorporation into cells and cell fractions. [³H]leu incorporation into total cell protein was inhibited by cortisol before measurable effects on extractable nuclear RNA polymerase were detected. Cortisol inhibition of [³H]leu incorporation into protein of nuclear extract (soluble at pH = 8.0) and protein associated with sucrose gradient purified RNA polymerase lagged behind [³H]leu incorporation into total cell protein but preceded the decrease in extractable RNA polymerase activity. These data suggest that the decrease in extractable RNA polymerase seen 12 hr after cortisol treatment is due, at least in part, to a decreased synthesis of the enzyme. The decrease in RNA polymerase activity, however, does not occur early enough to explain the marked inhibition of protein and RNA synthesis seen early (3 hr) after cortisol injection.