克百威及其代谢产物的小鼠骨髓红细胞微核试验研究

[目的]利用微核试验研究克百威及其4种代谢产物的遗传毒性。[方法]分别以0．1、0．2、0．4mg/kg3个不同剂量水平的克百威及其代谢产物3-羟基呋喃丹、3-酮基呋喃丹、呋喃酚和亚硝基呋喃丹腹腔注射染毒健康小鼠，24h后以同样剂量再次注射染毒，6h后脱颈椎处死动物，制片，观察并计数嗜多染红细胞的微核率，进行统计分析。[结果]克百威、呋喃酚及3-酮基呋喃丹小鼠胸骨骨髓嗜多染红细胞微核实验为阴性结果，高剂量处理组微核率分别为1．3‰、3．25‰和3．62‰，与阴性对照组(1．83‰)差异无显著性；而高剂量组3-羟基呋喃丹(7．00‰)和三个剂量组的亚硝基呋喃丹(微核率分别为3．62‰、5．00‰、7．85‰)均有明显微核效应。[结论]克百威、呋喃酚和3-酮基呋喃丹在受试剂量下微核试验阴性，3-羟基呋哺丹和亚硝基呋喃丹微核试验阳性，提示可能对染色体具有突变效应。     

MDR1特异性核酶逆转肝癌多药耐药的实验研究

目的探讨MDR1核酶（N2A＋tRNAi^met-iMDRl-sRz，sRz）在裸鼠体内逆转人肝癌组织多药耐药（MDR）的可行性。方法将原发性MDR人肝癌组织裸鼠原位移植模型第2代随机分为A组（空白对照组：生理盐水40μl＋Lipofect AMINE^TM2000 10μ1）、B组（阴性对照组：N2A＋tRNAi^met 10μg／40μl＋Lipofect AMINE^TM2000 10μl）和C组（核酶组：sRz 10μg／40μl＋LipofectAMINE^TM2000 10μl），均开腹瘤内注射。瘤内注药1周后用表阿霉素15mg／kg腹腔注射，每周1次，连续4周。彩色B超测量肿瘤体积。化疗结束后1周处死裸鼠，RT-PCR、Western blot法检测肿瘤中MDR1 mRNA及其蛋白P-gp的表达。结果C组每次化疗后肿瘤体积均较前缩小（F=659．99，P〈0．05）。除第1次化疗外，其余各次化疗后C组的抑制率均高于A、B组（F=35．36，12．77，97．60，P〈0．05）。化疗结束后，C组与瘤源以及A、B组相比，肿瘤组织中MDR1 mRNA和P-gp的表达明显降低（F=45．36，3590．40，P〈0．05）。结论sRz可有效降低肝癌细胞表达MDR1 mRNA和P-gp，一定程度上逆转MDR，提高E-ADM的化疗效果。单纯E-ADM化疗可使肝癌组织MDR1 mRNA和P-gp表达升高，诱导MDR的产生。     

人喉癌裸鼠移植瘤模型的建立及部分生物学特性研究

用人喉癌手术切除标本建立了裸鼠移植瘤模型,已传至13代。原代移植成功率为66.7％,潜伏期30～70d;鼠间传代移植成功率为100％,潜伏期14～19d,生长稳定。经光学显微镜检查,各代移植瘤组织结构与原人喉癌组织基本一致。电镜检查证明,具有人喉癌特征,癌细胞间有大量桥粒,细胞浆中可见张力原纤维,有的张力原纤维与桥粒相连。细胞表面有较大的指状突,核膜较规则,胞浆中线粒体较多。     

The effect of anti-IL-4 monoclonal antibody, rapamycin and interferon-γ on airway hyperreactivity to acetylcholine in mice

Background The role of IgE in airway hyperreaetivity is obscure. Objective In order to clarify the role of IgE in airway hyperreactivity, we investigated the effect of anti-IL-4 monoclonal antibody, rapamycin and interferon-γ on the antigen-induced IgE response, airway eosinophilia and hyperreactivity in mice. Methods Mice were immunized with an antigen (ovalbumin; OA) at intervals of 12 days. OA was inhaled 10 days after the secondary immunization. Twenty-four hours after the last inhalation, airway reactivity to acetylcholine was measured and bronchoalveolar lavage fluid (BALF) was obtained. Results Three inhalations of antigen caused an increase in the number of eosinophils in bronchoalveolar lavage fluid (BALF) and in airway hyperreactivity to acetylcholine with a significant elevation of serum IgE level. Anti-IL-4 at a dose of 1000 μg/animal and rapamycin at doses between 0.1 and 1 mg/kg inhibited the IgE production, but did not affect the airway eosinophilia or hyperreactivity to acetylcholine. In contrast, IFN-γ clearly inhibited the antigen-induced airway eosinophilia and hyperreactivity, but did not affect the IgE antibody production. Conclusion These results suggest that the inhibition of IgE production does not suppress the onset of airway hyperreactivity and eosinophilia in mice, and that IFN-γ inhibits the antigen-induced airway hyperreactivity, probably due to the inhibition of airway eosinophilia.     

The dynamic distribution of nitric oxide synthase in the small intestine of mice with intestinal radiation sickness

ＴｈｅｄｙｎａｍｉｃｄｉｓｔｒｉｂｕｔｉｏｎｏｆｎｉｔｒｉｃｏｘｉｄｅｓｙｎｔｈａｓｅｉｎｔｈｅｓｍａｌｌｉｎｔｅｓｔｉｎｅｏｆｍｉｃｅｗｉｔｈｉｎｔｅｓｔｉｎａｌｒａｄｉａｔｉｏｎｓｉｃｋｎｅｓｓＷｅｉＬｉｃｈｕｎ（魏丽春）；ＧｕｏＹａｏ（郭鹞）（...     

An Evolutionarily Conserved Region in the Second lntron of the Human Nestin Gene Directs Gene Exmession to CNS Progenitor Cells and to Early Neural Ciest Cells

Central nervous system (CNS) progenitor cells transiently proliferate in the embryonic neural tube and give rise to neurons and glial cells. A characteristic feature of the CNS progenitor cells is expression of the intermediate filament nestin and it was previously shown that the rat nestin second intron functions as an enhancer, directing gene expression to CNS progenitor cells. In this report we characterize the nestin enhancer in further detail. Cloning and sequence analysis of the rat and human nestin second introns revealed local domains of high sequence similarity in the 3' portion of the introns. Transgenic mice were generated with the most conserved 714 bp in the 3' portion of the intron, or with the complete, 1852 bp, human second intron, coupled to the reporter gene lacZ. The two constructs gave a very similar nestin-like expression pattern, indicating that the important control elements reside in the 714 bp element. Expression was observed starting in embryonic day (E)7.5 neural plate, and at E10.5 CNS progenitor cells throughout the neural tube expressed lacZ. At E12.5, lacZ expression was more restricted and confined to proliferating regions in the neural tube. An interesting difference, compared to the rat nestin second intron, was that the human intron at E10.5 mediated lacZ expression also in early migrating neural crest cells, which is a site of endogenous nestin expression. In conclusion, these data show that a relatively short, evolutionarily conserved region is sufficient to control gene expression in CNS progenitor cells, but that the same region differs between rodents and primates in its capacity to control expression in neural crest cells.     

Frequency of T-Cell Progenitors in Nude Mice

The hypothesis that prothymocytes are distinct from and regulated independently of multilineage hemopoietic progenitors was tested by enumeration of these two cell populations in normal versus congenitally athymic (nude) mice. The absence of a thymus and of peripheral T cells in nude mice had no effect on the frequency of either multilineage progenitors (day 12 CFU-S) or prothymocytes (CFU-T), suggesting that there is no feedback regulation of CFU-T frequency. Thymus seeding from the bone marrow is therefore likely to be regulated by the availability of niches for prothymocyte maturation, rather than by feedback control of prothymocyte production.     

小剂量氯化汞对小鼠脂质过氧化物的影响

本观察小剂量１ｍｇ／ｋｇ）ＨｇＣｌ２对小鼠肝，脑组织中脂质过氧化物（ＬＰＯ）的影响，发现小剂量ＨｇＣｌ２可使肝组织中ＬＰＯ含量明显增高，与对照组比，差异有显性（Ｐ〈０．０２５），而脑组织中ＬＰＯ含量未见明显影响（Ｐ〉０．０５）。