2-（4-氯苯氧乙基）-N-（1,2,3,4-四氢吖啶-9-基）乙酰胺对小鼠学习记忆的影响

目的探讨2-（4-氯苯氧乙基）-N-（1,2,3,4-四氢吖啶-9-基）乙酰胺对小鼠学习记忆的改善作用及作用机制。方法采用腹腔注射东莨菪碱造模,应用跳台实验观察化合物对小鼠学习记忆能力的影响,利用生化分析法测定脑组织中乙酰胆碱酯酶（AchE）和血清中丁酰胆碱酯酶（BuchE）的活性。结果在小鼠跳台实验中,与模型对照组相比,2-（4-氯苯氧乙基）-N-（1,2,3,4-四氢吖啶-9-基）乙酰胺25、15mg/kg组给药后小鼠潜伏期明显延长,5min内错误次数显著减少;脑内AchE活性显著下降,但对血清中BuchE活性无明显影响。结论 2-（4-氯苯氧乙基）-N-（1,2,3,4-四氢吖啶-9-基）乙酰胺对东莨菪碱小鼠有较明显的增强学习和记忆能力,该作用可能与其抑制脑内AchE活性有关。     

胺苯吖啶

胺苯吖啶(Amsacrine)的化学名称:4-(-9-吖啶基氨基)-甲烷磺酰-3-3氧 [作用与用途]胺苯吖啶是一个吖啶类抗癌药。其作用机理类似于蒽环类,它同腺嘌呤胸腺嘧啶碱基对有相互作用,因而在DNA复制和RNA合成过程中,能阻止DNA成为模板。其他还具有干扰细胞膜蛋白的结构作用,从而使之产生抗肿瘤活性。胺苯吖啶口服吸收差,通过静脉给药,每3～4周静脉给药一次(90～120mg/m~2)。它在肝内与谷胱甘肽结合而代谢,代谢物经     

东风桔化学成分的研究

从东风桔根中分离到一种新的吖啶酮类生物硷。根据紫外,红外,核磁共振谱和质谱等证明其结构为N-甲基-1,4,5-三羟基-3,6-二甲氧基吖啶酮-9,命名为东风桔碱B。     

阿霉素和安吖啶及其DNA复合物对小鼠的毒性和抗肿瘤作用

研究了阿霉素(ADR)和安吖啶(AMSA)与小牛胸腺DNA结合成复合物的药理特性。ADR与DNA的结合强度约相当AMSA的100倍。ADR—DNA复合物比ADR本身毒性小(LD_(50)提高0.45倍)。经ip后在小鼠S180三种实验模型(皮下、腹腔、静脉接种瘤)抗肿瘤作用增强。ADR—DNA较ADR吸收缓慢且血药浓度高2.5倍,药时曲线下面积(AUC)高2.8倍。ip后8h,心、肝、肺、肾、小肠和瘤中药物浓度,ADR—DNA组高于ADR组。AMSA—DNA和AMSA的毒性、AUC及抗癌作用无明显区别。     

阿霉素和安吖啶及其DNA复合物对小鼠的毒性和抗肿瘤作用

研究了阿霉素(ADR)和安吖啶(AMSA)与小牛胸腺DNA结合成复合物的药理特性。ADR与DNA的结合强度约相当AMSA的100倍。ADR—DNA复合物比ADR本身毒性小(LD₅₀提高0.45倍)。经ip后在小鼠S180三种实验模型(皮下、腹腔、静脉接种瘤)抗肿瘤作用增强。ADR—DNA较ADR吸收缓慢且血药浓度高2.5倍,药时曲线下面积(AUC)高2.8倍。ip后8h,心、肝、肺、肾、小肠和瘤中药物浓度,ADR—DNA组高于ADR组。AMSA—DNA和AMSA的毒性、AUC及抗癌作用无明显区别。     

东风桔化学成分的研究

从东风桔根中分离到一种新的吖啶酮类生物硷。根据紫外,红外,核磁共振谱和质谱等证明其结构为N-甲基-1,4,5-三羟基-3,6-二甲氧基吖啶酮-9,命名为东风桔碱B。     

胺苯吖啶(Amsacrine)

异名 NSC-156303,Acridinylaminom,M-AMSA,AMSA,SN-11841,NSC-141549,NSC-249992,Amsidene 化学名 4-(9-吖啶基氨基)甲烷磺酰-3-甲氧基苯胺盐酸盐药效分类抗肿瘤药开发单位 (瑞士)Ciba Geigy 上市厂商 (英)Parke Devis 1984年6月文献 J Med Chem 1976,19:1124 药理胺苯吖啶是第一个吖啶类抗癌药。它的作用机理类似于蒽环类;它与腺嘌呤-胸腺嘧啶碱基对相互作用,从而阻止DNA     

东风桔吖啶酮生物碱

自东风桔(Atalantia buxifolia)根分得11个化合物。经光谱分析和化学反应证明其中—新化合物结构为N-甲基-1,3-二羟基-2,5,6-三甲氧基吖啶酮-9,命名为东风桔碱。     

东风桔吖啶酮生物碱

自东风桔(Atalantia buxifolia)根分得11个化合物。经光谱分析和化学反应证明其中—新化合物结构为N-甲基-1,3-二羟基-2,5,6-三甲氧基吖啶酮-9,命名为东风桔碱。     

β-环糊精对依沙吖啶溶液稳定性的影响

目的探讨β-环糊精对依沙吖啶溶液稳定性的影响。方法采用避光条件下恒温加速试验和恒温条件下光照试验方法。结果β-环糊精对依沙吖啶溶液稳定性具有一定的保护作用。结论β-环糊精可作为依沙吖啶溶液的稳定剂。     

Synthesis of potential antitumor agents: nitrogen mustards based on quinoline

Benzaldehyde nitrogen mustard derivatives of hydrazinoquinolines, 9-hydrazinoacridine and 1,2,3,4-tetrahydro-9-hydrazinoacridine were synthesized; all compounds were tested against lymphocytic leukemia P388 and proved inactive.     

C1q/TNF-related protein-9 alleviates airway inflammation in asthma

BackgroundsAsthma is characterized as inflammatory disorder in the respiratory system with increasing tendency. Most of the asthma patients suffered from the disease since childhood. Thus, developing novel therapeutic targets of childhood asthma is necessary. Here, we conducted the present study to investigate the effects of CTRP9 (C1q tumor necrosis factor-related protein 9), a newly identified anti-inflammatory factor, on asthma.MethodsSixty asthmatic children (30 moderate and 30 mild) were recruited. The mRNA level of CTRP9 in peripheral blood mononuclear cells (PBMCs) and protein level of CTRP9 in serum and induced sputum (IS) samples from asthma patients and healthy controls (HCs) were measured by qPCR and ELISA, respectively. The anti-inflammatory effects of CTRP9 was determined in vitro and potential therapeutic effect on asthma was evaluated in mouse model.ResultsThe mRNA and protein levels of CTRP9 was significantly down-regulated in asthmatics than HCs. Furthermore, the expression level of CTRP9 was negatively correlated with the expression of TNF-α, IL-1β, and IL-6 in PBMCs. The CTRP9 significantly suppressed the expression of pro-inflammatory factors in PBMCs and sputum cells from asthma patients in vitro. And delivering CTRP9 into mouse model of asthma showed disease alleviation.ConclusionOur data here indicated that CTRP9 may alleviate airway inflammation and remodeling in asthma.     

地塞米松、吲哚美辛和白藜芦醇对巴豆油致炎小鼠耳部基质金属蛋白酶-9的抑制作用

目的研究巴豆油致炎小鼠耳部基质金属蛋白酶-9（MMP-9）的表达，以及地塞米松、吲哚美辛和白藜芦醇对MMP-9表达的影响。方法免疫组织化学法测定巴豆油致炎小鼠耳部MMP-9表达，明胶酶谱法测定U937细胞MMP-9表达。结果地塞米松和吲哚美辛以及白藜芦醇对巴豆油引起的小鼠耳肿胀有明显抑制作用；对巴豆油引起的小鼠耳部MMP-9表达以及PMA诱导的U937细胞MMP-9表达也有显著抑制作用。结论巴豆油致炎小鼠耳部MMP-9表达增高；地塞米松、吲哚美辛和白藜芦醇的抗炎作用可能与抑制MMP-9表达增高有关。     

抗H7N9流感病毒中和抗体快速检测方法的建立及应用

目的：对建立的抗H7N9流感病毒中和抗体快速检测方法进行方法学验证及初步应用。方法：分别采用不同代次细胞对高、中、低不同滴度的阳性血清进行多次平行检测,考察细胞代次对检验结果的影响;采用NIBSC提供的参考品对方法学的特异性进行验证;同时应用抗H7N9的阳性血清检测进一步评估方法的准确性和精密性;采用ELISA-MNT法和血凝抑制（hemagglutination inhibition,HI）试验分别接种H7N9灭活流感疫苗免疫的小鼠血清样本20份,分析两种方法检测结果的相关性。结果：采用ELISA-MNT中和法,使用不同代次MDCK细胞（25、30和35代）检测相同的血清样本的中和抗体滴度结果相同;该方法只对羊抗H7N9的血清具有较高保护力,对其他血清基本没有交叉反应;该方法准确性良好;该方法组间、组内精密性的平均变异系数分别为4%和11%。该方法测定H7N9型流感疫苗免疫后的小鼠血清抗体效价,其结果与HI抗体的相关系数为0.61,表明两种方法的检测结果之间呈良好的正相关性。结论：建立的微量病毒中和法能够满足H7N9流感病毒中和抗体效价检测的要求,可用于H7N9新型大流行流感疫苗的免疫评价。     

Enhanced efficacy of the acyclic nucleoside 9-(1,3-dihydroxy-2-propoxymethyl)guanine in combination with gamma interferon against herpes simplex virus type 2 in mice

The acyclic nucleoside 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG) and recombinant mouse interferon gamma (rMuIFN-gamma) were evaluated for their efficacy alone and in combination against a herpes simplex virus type 2 systemic infection in mice. Intraperitoneally infected animals were treated once a day with the drugs at various concentrations for 5 days starting 24 h after inoculation. DHPG was given subcutaneously and rMuIFN-gamma intraperitoneally. For DHPG, the effective dose at which 50% of the mice survived (ED50 was lowered approximately 10-fold from 3.4 to 0.25 mg/kg when given in combination with an ineffective dose of 4MuIFN-gamma (10(3) units per mouse). For rMuIFN-gamma, the ED50 was lowered greater than 10-fold from 6 x 10(3) to less than 3 x 10(2) units per mouse when given in combination with a marginally effective dose of DHPG (1 mg/kg). Construction of an isobologram and calculation of the corresponding fractional protective dose index (less than 0.12 where values less than or equal to 0.5 are considered synergistic) indicates an enhanced protective interaction by the combination of the two drugs.     

原始心肌的存在对小鼠胚胎心脏流出道心内膜特征的维持作用

目的　观察小鼠胚胎心脏流出道原始心肌对心内膜特征的影响。方法　用抗α 横纹肌肌节肌动蛋白抗体 (α SCA) ,抗α 平滑肌肌动蛋白抗体 (α SMA)单克隆抗体对胚龄 9～ 11d小鼠胚胎心脏连续切片进行染色。结果　流出道远侧部原始心肌转分化成升主动脉、肺动脉干近半月瓣处的游离壁后 ,心内膜特征发生改变。结论　小鼠胚胎心脏流出道心内膜特征的维持依赖于原始心肌的存在     

Effects of Delta9-tetrahydrocannabivarin on [35S]GTPgammaS binding in mouse brain cerebellum and piriform cortex membranes

BACKGROUND AND PURPOSE: We have recently shown that the phytocannabinoid Delta9-tetrahydrocannabivarin (Delta9-THCV) and the CB1 receptor antagonist AM251 increase inhibitory neurotransmission in mouse cerebellum and also exhibit anticonvulsant activity in a rat piriform cortical (PC) model of epilepsy. Possible mechanisms underlying cannabinoid actions in the CNS include CB1 receptor antagonism (by displacing endocannabinergic tone) or inverse agonism at constitutively active CB1 receptors. Here, we investigate the mode of cannabinoid action in [35S]GTPgammaS binding assays. EXPERIMENTAL APPROACH: Effects of Delta9-THCV and AM251 were tested either alone or against WIN55,212-2-induced increases in [35S]GTPgammaS binding in mouse cerebellar and PC membranes. Effects on non-CB receptor expressing CHO-D2 cell membranes were also investigated. KEY RESULTS :Delta9-THCV and AM251 both acted as potent antagonists of WIN55,212-2-induced increases in [35S]GTPgammaS binding in cerebellar and PC membranes (Delta9-THCV: pA2=7.62 and 7.44 respectively; AM251: pA2=9.93 and 9.88 respectively). At micromolar concentrations, Delta9-THCV or AM251 alone caused significant decreases in [35S]GTPgammaS binding; Delta9-THCV caused larger decreases than AM251. When applied alone in CHO-D2 membranes, Delta9-THCV and AM251 also caused concentration-related decreases in G protein activity. CONCLUSIONS AND IMPLICATIONS: Delta9-THCV and AM251 act as CB1 receptors antagonists in the cerebellum and PC, with AM251 being more potent than Delta9-THCV in both brain regions. Individually, Delta9-THCV or AM251 exhibited similar potency at CB1 receptors in the cerebellum and the PC. At micromolar concentrations, Delta9-THCV and AM251 caused a non-CB receptor-mediated depression of basal [35S]GTPgammaS binding.     

Role of aquaporin 9 in cellular accumulation of arsenic and its cytotoxicity in primary mouse hepatocytes

Aquaporin (AQP) 9 is a member of the aquaglyceroporin subfamily of AQPs in the transfer of water and small solutes such as glycerol and arsenite. It is well recognized that arsenic toxicity is associated with intracellular accumulation of this metalloid. In the present study, we examined the contribution of AQP9 to the uptake of inorganic arsenite, thereby increasing arsenic-induced cytotoxicity in primary mouse hepatocytes. Pretreatment with sorbitol as a competitive inhibitor of AQP9 and siRNA-mediated knockdown of AQP9 resulted in a significant decrease of arsenite uptake in the cell and its cytotoxicity. Furthermore, overexpression of AQP9 in HEK293 cells led to the enhancement of intracellular arsenic concentration, resulting in enhanced cytotoxicity after arsenite exposure. These results suggest that AQP9 is a channel to define arsenite sensitivity in primary mouse hepatocytes.     

BAPTA-AM对HepG-2细胞MT的保护作用及其机制

目的观察BAPTA-AM抗H2O2诱导的HepG-2细胞MT损伤作用并探讨其机制。方法采用四甲基偶氮唑盐比色(MTT)、Rhodamine 123(Rh 123))荧光染色、细胞色素C酶联免疫分析、Caspase-9活性检测试剂盒、活性氧ROS检测法分别测定HepG-2细胞活性、线粒体(MT)膜电位、MT细胞色素C(CytC)的释放、Caspase-9的激活、活性氧(ROS)的产生量。结果 BAPTA-AM能抑制H2O2损伤HepG-2细胞所致MT跨膜电位的降低,减少CytC的释放,抑制Caspase-9激活和ROS的生成,提高受攻击H2O2的细胞活力。结论 BAPTA-AM通过减轻钙超载,保护MT,抑制凋亡通路的激活,产生抗细胞损伤、挽救细胞生命之效。     

Soluble Siglec-9 alleviates intestinal inflammation through inhibition of the NF-κB pathway

BackgroundSialic acid-binding immunoglobulin-like lectins (Siglecs) are a superfamily of immunoreceptors recognizing sialic acid. Siglec-9 has been shown to mediate inhibitory immune responses. The aim of this study was to evaluate the effect of a soluble form of Siglec-9 (sSiglec-9) on inflamed intestinal epithelial cells (IECs), murine macrophages, and experimental murine colitis models.MethodsCOLO 205 human IECs and RAW 264.7 murine macrophages were pretreated with sSiglec-9 and then stimulated with TNF-α or lipopolysaccharides, respectively. The expression of proinflammatory cytokines such as IL-8 and TNF-α was measured using real-time RT-PCR and ELISA. To demonstrate the inhibitory effects of sSiglec-9 on the NF-κB pathway, IκBα phosphorylation/degradation was determined using western blotting and the DNA binding activity of NF-κB was evaluated using an electrophoretic mobility shift assay. Further, mouse models with dextran sulfate sodium-induced acute colitis and piroxicam-induced IL-10^-/- chronic colitis were generated. Intraperitoneal injections of sSiglec-9 were performed, and body weight, colon length, and histopathologic findings were examined.ResultssSiglec-9 suppressed IL-8 and TNF-α gene expression in stimulated COLO 205 and RAW 264.7 cells. sSiglec-9 inhibited IκBα phosphorylation/degradation and the DNA binding activity of NF-κB. sSiglec-9 injections significantly ameliorated weight loss, colon shortening, and the severity of intestinal inflammation in acute and chronic colitis mouse models.ConclusionsSiglec-9 may inhibit NF-κB activation in IECs and macrophages and alleviate experimental colitis in mice, suggesting that sSiglec-9 is a potential therapeutic agent for the treatment of inflammatory bowel disease.