鹿茸有效成分对小鼠肝脏RNA和蛋白质合成的影响

多次给小鼠po鹿茸多胺30mg/kg,对[³H]leucine和[³H]uridine掺入肝组织蛋白和RNA有明显的促进作用,而庸茸非多胺则无此作用;当腐胺剂量为21mg/kg时,不仅促进[³H]leucine和[³H]uridiae掺入肝组织蛋白和RNA,也促进[³H]uridine掺入肝细胞核的RNA中,并增强RNA聚合酶的活性;精脒在剂量为8mg/kg时,仅对[³H]leucine掺入肝组织蛋白有促进;而精胺在1mg/kg时,没有观察到上述各种现象。此结果提示,鹿茸多胺类物质是鹿茸中刺激小鼠肝组织蛋白和RNA合成的主要活性物质,这 种刺激小鼠肝组织蛋白和RNA合成效应是由于鹿茸多胺能够显著地增强RNA聚合酶的活性。     

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。     

三七皂甙C1对四氧嘧啶糖尿病小鼠的降血糖作用

三匕皂甙Cl(简称Cl)能降低四氧嘧啶糖尿病小鼠血糖,效应随连续给药而增强,并呈量—效关系趋势,与胰岛素的降糖效应无协同或拮抗作用。单剂量Cl对四氧嘧啶糖尿病小鼠的血浆胰岛素和肝脏cAMP浓度无明显影响;但能促进大鼠分离肝细胞摄取[³H]葡萄糖,还能增加小鼠肝匀浆代谢葡萄糖和琥珀酸钠的耗氧量以及小鼠肝糖原的合成。     

四氢巴马汀等异喹啉生物碱对突触体及囊泡摄取[3H]多巴胺的影响

本文报道四氢巴马汀(THP)等异喹啉生物碱对[³H]DA摄取的作用。突触体对[³H]DA的亲和力常数Km为0.23μmol。最大摄取速率Vmax为1.2 nmol/g(5 min)。d-THP,1-SPD和1-THP对突触体摄取[³H]DA均有抑制作用,其IC₅₀分别为0.44,2.24和18.5μmol。d-THP的作用比1-THP约强20倍。nomifensine,苯丙胺和氟哌啶醇亦能有效地抑制[³H]DA摄取(IC₍₅₀₎分别为0.05,0.27和3.18μmol)。动力学研究表明,d-THP和nomifensine为DA摄取的竞争性抑制剂。用低渗溶液处理溶胀的方法研究药物对递质贮存的作用发现,与利血平相似,d-THP显著降低贮存囊泡[³H]DA含量并使囊泡与突触体[³H]DA含量之比明显减小。实验结果表明,THP等能抑制突触体摄取,并直接作用于贮存囊泡抑制[³H]DA贮存,因此具有利血平样排空作用。     

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。     

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。     

鹿茸多肽促进表皮和成纤维细胞增殖及皮肤创伤愈合

目的　研究总鹿茸多肽(TVAP)及天然鹿茸多肽(nVAP)和合成鹿茸多肽(sVAP)对细胞增殖的影响。方法分离乳鼠表皮细胞和家兔肋软骨细胞,体外加入TVAP ,nVAP和sVAP ,观察其对[3H]TdR参入细胞DNA合成的影响。整体观察TVAP对大鼠实验性皮肤损伤的修复作用。结果　TVAP 0.8和3.2mg·g^-1 膏剂外涂对实验性大鼠皮肤损伤有加速修复作用。离体TVAP 5 - 50mg·L^-1 和nVAP 0.4 - 50mg·L^-1 均能促进大鼠表皮细胞有丝分裂,提示nVAP是TVAP中促进表皮细胞分裂和加速皮肤创伤愈合的主要活性多肽。sVAP对表皮细胞和成纤维细胞增殖有促进作用。结论　马鹿茸多肽通过促进表皮细胞和成纤维细胞增殖加速皮肤创伤愈合。     

重组小鼠β防御素3体内抗甲型流感病毒H1N1作用

目的 观察重组小鼠β防御素3(rMBD3)对甲型流感病毒感染小鼠的保护作用。方法 以10 mg·kg^-1·d^-1rMBD3腹腔注射3月,观察小鼠的一般状态,以及对主要脏器的影响。BALB/c小鼠,♀,分为正常对照组、模型对照组、rMBD3高剂量组(10 mg·kg^-1·d^-1)、rMBD3低剂量组(5 mg·kg^-1·d^-1)和利巴韦林组(100 mg·kg^-1·d^-1)。采用流感病毒液滴鼻感染建立甲型流感病毒H1N1感染小鼠模型,感染病毒12 h后分别腹腔注射给药。每日观察小鼠一般情况和死亡情况。于攻毒第3天检测肺泡灌洗液流感病毒滴度、血清γ干扰素含量、肺指数和肺组织病理变化。结果 小鼠腹腔注射10?mg·kg^-1·d^-1 rMBD3 3月,未发现明显异常反应或死亡,各重要脏器的未见明显病理改变。rMBD3各剂量组肺泡灌洗液中的病毒滴度、肺指数抑制率均降低,肺组织病理改变减少。结论 rMBD3对小鼠无明显毒性作用,在体内具有抗流感病毒、保护流感小鼠的活性。     

北京鸭红细胞膜β肾上腺素受体放射配基结合测定法

本文以[³H]dihydroalprenolol([³H]DHA)为放射配基。对北京鸭红细胞(RBC)膜β受体进行了系统研究。结果表明,[³H]DHA与北京鸭RBC结合具有饱和性,肾上腺素能激动剂与[³H]DHA竞争结合的强弱顺序与它们的生物活性一致,提示结合有结构特异性和立体特异性,[³H]DHA与鸭RBC结合迅速、可逆。可见北京鸭RBC膜存在β受体,用于放射配基结合测定有取材方便,受体较丰富,膜蛋白得率高,[³H]DHA非特异结合低和易于保存等优点,可以代替火鸡RBC。     

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.     

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.     

Partial characterization of specific cantharidin binding sites in mouse tissues

The mode of action of cantharidin, the natural vesicant of blister beetles, is examined by radioligand binding studies with mouse tissues. [3H]Cantharidin undergoes specific and saturable binding with the liver cytosol, which is characterized as follows: Kd and Bmax values of 30 nM and 1.8 pmol/mg of protein, respectively; linearity with respect to protein concentration; pH optimum of 6.5 to 7.5; association and dissociation half-times of 20 min and 12 hr, respectively; and 50% inhibition by Mg2+ at 70 microM, Ca2+ at 224 microM, pyrophosphate at 27 microM, and nucleotide triphosphates at 52-81 microM. The binding site undergoes a loss of activity at 45 degrees or higher. The toxicological relevance of this specific [3H]cantharidin binding site of mouse liver cytosol is established in three ways. First, the potency of 15 active cantharidin analogs for inhibiting [3H]cantharidin binding is correlated with their acute toxicity to mice (r = 0.829). Second, 26 related compounds that are inactive in inhibiting [3H]cantharidin binding are also of little or no toxicity to mice. Finally, the binding of [3H] cantharidin to liver cytosol from mice poisoned with increasing amounts of unlabeled cantharidin is inhibited in a dose-dependent manner. [3H]Cantharidin also specifically binds to cytosol fractions of blood, brain, heart, kidney, lung, pancreas, skin, spleen, and stomach. The characteristics of the specific binding site in brain are very similar to those determined in liver with respect to Kd, Bmax, association/dissociation kinetics, and sensitivity to inhibitors. It therefore appears that the toxicity of cantharidin and related oxabicycloheptanes, including the herbicide endothal, is attributable to binding at a specific site in liver and possibly other tissues.     

槲皮素对血管紧张素Ⅱ致培养乳鼠心肌细胞肥大的抑制作用

目的:研究槲皮素(Quercetin,Que)对血管紧张素Ⅱ(Aug Ⅱ)诱发培养乳鼠心肌细胞肥大的抑制作用及机制。方法:分别用[~3H]胸苷、[~(14)C]尿苷和[~3H]酪氨酸标记测定DNA、RNA和蛋白质合成;用Lowry法测定蛋白质含量;用组蛋白ⅢS、[γ-~(32)P]ATP与蛋白激酶C(PKC)酶液一起保温测定PKC活性;用聚谷氨酸·酪氨酸(4:1)多肽、[γ-~(32)P]ATP与酪氨酸蛋白激酶(TPK)酶液一起保温测TPK活性。结果:Aug Ⅱ作用于心肌细胞24h后,心肌细胞总蛋白含量明显增加(P<0.01),[~(14)C]尿苷和[~3H]酪氨酸掺入量明显增加(P<0.01),而[~3H]胸苷掺入量未见增加(P>0.05);Aug Ⅱ作用30min后,心肌细胞PKC和TPK活性明显增加。Que(1-100μmol/L)能剂量依赖性地抑制Ang Ⅱ所致心肌细胞总蛋白含量、[~(14)C]尿苷和[~3H]酪氨酸掺入量、PKC及TPK活性的增加。结论:Que可抑制Aug Ⅱ致培养乳鼠心肌细胞肥大,该作用与抑制PKC及TPK活性有关。     

Possible nuclear protein kinase regulation of homologous ribonucleic acid polymerases from small dense nuclei of mouse brain during morphine tolerance-dependence. Involvement of cyclic 3',5'-adenosine monophosphate

A correlation between phosphorylation and stimulation of RNA polymerases I and II by homologous nuclear protein kinase peak I from small dense nuclei of mouse brain was demonstrated. Incubation of RNA polymerase II with nuclear protein kinase peak I lowered the optimum Mg²⁺ concentration of the polymerase in the same manner as chronic morphine treatment alone did, suggesting that the change in Mg²⁺ optimum of RNA polymerase II seen during morphine tolerance-dependence may occur through changes in phosphorylation as a result of increased nuclear protein kinase activity. Experiments investigating the involvement of cyclic 3',5'-adenosine monophosphate (cAMP) in morphine tolerance-dependence demonstrated that dibutyryl-cAMP enhanced the degree of morphine tolerance developed, as reported previously [I. K. Ho, H. H. Loh and E. L. Way, J. Pharmac. exp. Ther.185, 347 (1973); I. K. Ho, H. H. Loh, H. N. Bhargava and E. L. Way, Life Sci.16, 1895 (1975)], and also enhanced the chronic morphine-induced increase in nuclear protein kinase specific activity. Alterations in the regulation of the nuclear protein kinase activity may bave subsequently affected RNA polymerase activity through phosphorylation. These results suggest that, during morphine tolerance-dependence development, cAMP may be involved in the possible nuclear protein kinase regulation of homologous RNA polymerase.     

A comparison of mirex-induced liver growth to liver regeneration

In intact rats given a single oral dose of mirex there was a dose-dependent increase in liver weight which peaked at 4 days. There were increases in hepatic RNA and protein, but DNA content per liver and DNA synthesis as measured by [3H]thymidine incorporation were unchanged. In partially hepatectomized rats dosed with mirex 24 h post-surgery, there was a dose-dependent increase in relative liver weight which peaked at 5 days. In partially hepatectomized rats simultaneously dosed with mirex, [3H]thymidine incorporation into DNA was unaltered. However, in rats dosed with mirex 24 h prior to partial hepatectomy, there was a 50% reduction in [3H]thymidine incorporation into hepatic DNA.     

The mechanisms of the inhibitory effects of liver extract on lymphocyte proliferation. III. The effects of arginase on DNA polymerase activities

The incorporation of labeled precursors into DNA, RNA and protein in phytohaemagglutinin (PHA)-prestimulated human lymphocytes was maximally inhibited by liver extract (LEx) or arginase at 24 h. The activities of DNA polymerase alpha, beta and gamma were less inhibitable by these agents than was [3H]thymidine incorporation. The inhibition of DNA, RNA and protein syntheses by either LEx or arginase is probably due to arginine depletion by arginase activity, since their syntheses were similarly inhibited when cultured in an arginine-free medium in the absence of arginase. These results indicate that arginase nonspecifically inhibits the activities of DNA polymerase. The inhibition is probably due to arginine depletion.     

ACTH and the stress-induced changes of lysine incorporation into brain and liver proteins.

When mice were subjected to footshock treatment and subsequently injected with [3H] lysine, the cerebral uptake of [3H] lysine, its incorporation into brain protein and the relative radioactivity (RR = protein radioactivity divided by amino acid radioactivity) were all increased. In the liver, footshocked mice showed decreased free lysine radioactivity, and increased protein radioactivity and relative radioactivity compared to quiet mice. The possibility that ACTH mediated these effects was investigated. The injection of saline had no effect in the brain but partially mimicked the footshock responses in the liver. Injections of ACTH 1--24 mimicked the effects of footshock in the brain, and further augmented the saline-induced effect on the RR in the liver. ACTH 4--10 increased the RR of brain protein, but produced no significant change in brain free lysine radioactivity or in any measure in the liver. Pretreatment of mice with the synthetic glucocorticoid, dexamethasone, did not enhance these effects and diminished the effect of ACTH 4--10 in the brain. ACTH treatment did not alter the profiles of brain polyribosomes. Lysine vasopressin, which is also released during stress, did not alter the incorporation of [3H] lysine into brain or liver protein, except at high doses when it decreased plasma radioactivity. These results suggest that secretion of ACTH at least partially mediates the stress-induced changes of [3H] lysine incorporation into brain and liver proteins, but that it is probably not the only factor involved.