bcl-xs基因对卵巢癌的作用及其凋亡机制的研究

目的 :研究全反式维甲酸 (ATRA)抑制视网膜母细胞瘤 (Rb)细胞生长的作用及信号转导机制。方法 :应用3 H 胸腺嘧啶掺入分析法观察ATRA对细胞生长的抑制作用 ,用流式细胞仪分析ATRA对Y79细胞周期的影响 ,用Westernblot分析c jun氨基末端激酶 (JNK)的磷酸化。 结果 :ATRA可明显地抑制Y79细胞的生长 ,10 -6mol·L-1ATRA处理 36h时 ,3 H 胸腺嘧啶掺入率下降达 4 0 % ,此条件下 ,Y79细胞被阻滞于G0 /G1期 ,并出现Sub G1峰 ;此生长抑制过程可被JNK的阻断剂Curcumin阻断 ;在此过程中 ,JNK被激活 ,磷酸化。结论 :ATRA可抑制Y79细胞生长 ,其过程是由磷酸化的JNK介导。提示 ,ATRA可能是一种潜在的抗视网膜母细胞瘤治疗药物     

CeReS-18, a novel cell surface sialoglycopeptide, induces cell cycle arrest and apoptosis in a calcium-sensitive manner

Very few growth inhibitors have been identified whichcan inhibit the proliferation of a broad spectrumof human breast cancer cell lines. CeReS-18, anovel cell surface sialoglycopeptide growth inhibitor, can reversiblyinhibit the proliferation of both estrogen receptor positive(MCF-7) and negative (BT-20) human breast cancer celllines. In addition, at concentrations above those requiredfor the reversible inhibition of cell proliferation, CeReS-18can also induce cell death in MCF-7 cells.Changes in nuclear and cytoplasmic morphology, characteristic ofapoptosis, were detected in MCF-7 cells treated witha cytotoxic concentration of CeReS-18, and internucleosomal DNAcleavage was also observed. The sensitivity of MCF-7and BT-20 cells to the biological properties ofCeReS-18 could be influenced by altering the calciumconcentration in the extracellular growth medium, such thatwhen the calcium concentration in the environment wasdecreased, an increased sensitivity to CeReS-18-induced growth inhibitionand cytotoxicity were observed. The addition of thecalcium chelating agent EGTA to MCF-7 cells, culturedin a normal calcium environment, could mimic theincreased sensitivity to the biological effects of CeReS-18observed under reduced calcium conditions.     

黄连与黄芩、甘草配伍前后对金黄色葡萄球菌生长抑制作用的观察

以ＭＩＣ相对值为指标，观察黄连、黄芩、甘草煎液单味或不同比例配伍后对金黄色葡萄球菌生长的抑制作用。结果显示：黄连与黄芩配伍，黄芩的抑菌作用有所降低，但黄连则未见降低；黄芩多于黄连时，黄连的抑菌作用似有增强。黄连与甘草配伍，无论比例如何，配伍后的抑菌作用均呈降低趋势。当三药同时配伍时，黄连、甘草的抑菌作用不变，或反增强，只有黄芩的抑菌作用有减弱趋势。黄连与黄芩、甘草两两配伍，单独使用时，其抑菌作用似不如组成三药配伍。其机制值得进一步研究。     

Clotrimazole, an Imidazole Antimycotic, Is a Potent Inhibitor of Angiogenesis

Clotrimazole, an imidazole antimycotic, interferes with the rise in cytosolic Ca²⁺ and inhibits cell proliferation in a reversible manner. Here we describe the effect of clotrimazole on vascular endothelial cells (ECs). Clotrimazole inhibited the proliferation of ECs stimulated with typical angiogenic growth factors; vascular endothelial growth factor and basic fibroblast growth factor (bFGF). This inhibitory effect of clotrimazole was dose-dependent and the maximal inhibition was observed at a concentration of 10 m M . We did not observe any increase in ⁵¹Cr release from ECs during treatment with 10 μ M . clotrimazole. Moreover, clotrimazole inhibited the basal and bFGF-stimulated migration of ECs. As clotrimazole inhibited two principle components of angiogenesis; the proliferation and migration of ECs, we examined whether clotrimazole inhibited angiogenesis. Tube formation by ECs in type 1 collagen gel was investigated, and clotrimazole was found to be significantly inhibitory. The inhibitory effect of clotrimazole on angiogenesis was further confirmed in an in vivo angiogenesis model of murine Matrigel plug assay. These results demonstrate that clotrimazole is a potent inhibitor of angiogenesis.     

槲皮素等中药成分对蛋白非酶糖化的体外抑制研究

目的:从部分中药成分中筛选新的非酶糖化(NEG)抑制荆,探讨其可能的作用机制。方法:通过建立体外牛血清白蛋白 NEG 系统以模拟糖尿病的体内环境,测定16种中药成分在不同浓度梯度(1×10~(-1)～1×10~(-7)mg/ml)下对糖化终末产物(AGEs 的荧光抑制率及半效抑制浓度(IC_(50)),并与公认的 NEG 抑制剂——氨基胍(AG)作比较。结果:槲皮素、芦丁、羟乙基芦丁、黄芩甙元、黄芩甙、水飞蓟素等具有明显的 NEG 抑制作用,其 IC_(50)分别为0.86mg/L、1.16mg/L、1.64mg/L、2.36mg/L、4.71mg/L 与1.75mg/L,相应的 AG 为0.38mg/L;部分补中益气类中药,其皂甙也有一定的 NEG 抑制作用,但较 AG 弱。结论:槲皮素等6种黄酮类中药在抑制体外蛋白 NEG 作用方面与 AG 相近,但机制可能与 AG 不同。某些抗衰老药物的作用机制可能与抑制蛋白 AGEs 形成有关。     

相恶研究探析

相恶作为中药七情配伍之一,最早见于汉代《神农本草经》。李时珍在《本草纲目》中论述相恶时云:“相恶者,夺我之能也。”后世多沿袭之。现代教科书多将相恶定义为:两种药物合用,一种药物与另一种药物相作用而致原有功效降低,甚至丧失。笔者对相恶的历史源流进行了考证并对其理论和实验研究进展作一探讨。     

三氧化二砷抑制人膀胱癌 EJ细胞增殖及其作用机制探讨

背景与目的:观察三氧化二砷(Arsenictrioxide,As2O3)对人膀胱癌EJ细胞生长抑制作用,并探讨其作用机理。材料与方法:四甲基偶氮唑蓝(3_[4,5_dimethylthiazol_2_yl]_2,5diphenyltetrazoliumbromid,MTT)法检测EJ细胞增殖活力;荧光染色观察凋亡细胞的形态学变化;流式细胞术分析细胞周期及细胞凋亡;免疫细胞化学染色观察caspase_3蛋白的表达。结果:As2O3 与EJ细胞生长抑制率之间有显著的浓度依赖关系,IC50 为22.51μmol/L;荧光显微镜下观察到经As2O3 作用后,EJ细胞出现凋亡现象;流式细胞术结果表明20μmol/L的As2O3 处理EJ细胞48h后,细胞周期变化无显著性差异,细胞凋亡率从对照组的3.37 %上升到19.07 %;免疫细胞化学染色结果显示,20μmol/L的As2O3 处理EJ细胞48h后,能够诱导caspase_3蛋白的表达。结论:As2O3 能显著抑制EJ细胞增殖,诱导caspase_3蛋白表达,并进一步诱导细胞凋亡。     

药物代谢中的药酶特性与临床研究近况

目的:为了促进药物代谢酶在临床上的深入研究。方法:以近几年国内外大量有代表性的论文为依据进行分析、归纳、整理。结果:药物代谢酶大多具有遗传多态性,其活性受相关药物影响,遗传多态性和药物之间代谢性相互作用是临床药物反应千变万化的重要因素。结论:药物代谢酶的认识和研究有助于临床合理用药和减少药物不良反应。     

全球历年人甲型流感病毒H3A1抗原的分子进化研究

目的应用生物信息学数据库和工具，对现有的H3N2亚型人甲型流感病毒全球分离株的H3A1抗原序列进化规律进行分析研究。方法下载NCBI Genbank和流感病毒数据库中全部的甲型流感病毒H3A1序列，首先用两步聚类法进行样本拆分，随后分类绘制出完整的进化树。结果人H3A1序列呈现出单一主干的进化趋势，随着时间的推移，进化树结构和进化模型相关参数均呈现出一定的变化规律，关键变异株的出现则无明显的地域分布特征。结论人流感病毒H3A1抗原的进化主要是病毒抗原漂移和人类免疫选择相互作用的结果，新变异株的出现并未出现明显的地域倾向性，中国华南地区不应当被认为是H3亚型新变异株的发源地。     

Modulation of triceps surae H-reflexes as a function of the reflex activation history during standing and stepping

The facilitatory effectiveness of spindle afferent feedback is controlled by modulation of segmental reflex excitability such that the level of muscle activation is appropriate for the task. Phase-dependent modes of reflex modulation have been well-characterized. We hypothesized that segmental reflex excitability of the triceps surae was also modulated in a manner associated with the activation history of the spindle afferents and the segmental reflex pathway during isometric contractions, standing and stepping. In the first experiment. pairs of soleus (S) H-reflexes were evoked 80 ms apart with equal strength stimuli at rest and while subjects isometrically contracted their S against loads of 10%. 20%. and 50% of their maximum voluntary efforts. The percent depression of the second H-reflex relative to the first was used as a measure of the effect of reflex activation history. At rest, the second H-reflexes were depressed an average of 73% relative to the first. The degree of depression was progressively reduced as the plantarflexion torque increased. In the second experiment, paired H-reflexes were obtained from the S and medial (MG) and lateral gastrocnemii (LG) muscles while subjects were standing and during the stance phase of step initiation. The degree of depression of the second H-reflex during standing ( > 78%) was similar in magnitude to that produced at rest in Experiment I. At the end of the stance phase of stepping. depression of the second H-reflex of all three muscles was reduced to less than 25%. We conclude that the segmental reflex excitability is modulated as a function of the reflex activation history during these tasks.