脐血源性T淋巴细胞在白血病小鼠体内存活及浸润状况的研究

目的研究脐血源性T淋巴细胞在小鼠体内的存活、浸润情况,为深入探讨脐血源性T淋巴细胞过继性输注治疗白血病提供实验和理论依据。方法24只红白血病小鼠随机分为对照组和试验组。将分离制备的脐血源性T淋巴细胞标记后经尾静脉移植入白血病小鼠体内,采用免疫荧光、免疫组织化学等方法观察脐血源性T淋巴细胞在小鼠体内的存活时间及浸润状况。结果①移植后第3、7、14天在实验组小鼠外周血、肝和脾组织中均可检测到人CD3+细胞和Brdu+细胞;②实验组小鼠肝、脾组织内均见CD25+细胞散在浸润。结论脐血源性T淋巴细胞能在白血病小鼠体内存活并趋化至白血病细胞浸润部位。     

生长抑素类似物抑制胆管癌细胞增殖的研究

目的探讨生长抑素类似物奥曲肽(OCT)对人胆管癌细胞细胞株QBC939的抑制作用及可能的作用机制。方法四氮唑蓝(MTT)法检测OCT对人胆管癌细胞株QBC939增殖的影响,流式细胞仪检测OCT对细胞周期变化的作用,免疫组织化学法研究OCT对人胆管癌细胞株QBC939P27KIP1蛋白表达变化的影响。建立胆管癌裸鼠模型,进一步探讨生长抑素的作用。结果MTT法检测不同浓度OCT(5、0.5、0.05、0.005mg/L)作用于QBC93948h后,实验组0.5、5mg/L组和对照组吸光度(A)值比较差异有统计学意义(P<0.05)。细胞生长率分别为83.80%,80.28%,77.53%,65.32%。流式细胞仪分析显示不同浓度OCT作用于QBC93948h后,G0/G1期细胞明显增多(P<0.05)。免疫组织化学P27KIP1蛋白表达随OCT浓度的增加而增强(P<0.05)。建立胆管癌裸鼠模型后,OCT干预21d后实验组瘤重明显小于对照组(P<0.05)。结论OCT可抑制人胆管癌细胞的增殖。在一定范围内呈剂量依赖性,其抗肿瘤作用机制主要是通过细胞周期阻滞来实现的,而这一作用的实现可能与P27KIP1蛋白表达的上调有关。     

4个与营养代谢相关基因对小鼠的血清生化指标的影响

目的研究4个与营养代谢相关基因(DL、Tr、Pe、P3)对BALB/c小鼠的血液生化指标的影响。方法将4个基因的反义核酸微量定量注入小鼠侧脑室。设反义核酸实验组、随机序列核酸对照组和生理盐水对照组3组;3次注射后于第4天取血清进行生化指标测定。结果DL和Tr实验组与对照组分别在6项指标上有显著性差异,Pe实验组、P3实验组与对照组分别有4项和3项指标有显著性差异。结论3个反义核酸实验组(DL、Tr和P3)BABL/c小鼠的血中甘油三酯含量都显著高于对照组,尤其是Tr反义核酸实验组的胆固醇含量也显著高于对照组,且都超出正常值范围,进一步证明Tr基因与脂类代谢有一定的相关性。另外上述3个反义核酸实验组(DL、Tr和P3)的血中葡萄糖含量也明显高于对照组并超出正常值范围,说明这些基因还可能与糖代谢相关。     

呼吸道合胞病毒诱发的哮喘小鼠模型的建立

[目的]探讨建立呼吸道合胞病毒诱发的哮喘小鼠模型的方法，为研究哮喘发病机理、筛选有效的治疗药物奠定基础。[方法]随机将BALB／C小鼠分成正常对照和模型组两组。用福尔马林灭活的呼吸道合胞病毒（FI-RSV）致敏、激发模型组小鼠，观察激发后小鼠的哮喘症状；分别于激发后0、24、48、72h处死动物，摘眼球取血分离血清，ELISA测定血清IgE、IL-4、IFN-γ水平；取肺组织行HE染色，观察支气管黏膜及黏膜下炎症细胞浸润及EOS的浸润情况。[结果]模型组小鼠激发即刻可见典型的哮喘症状。激发后24h肺组织炎症细胞浸润最多。模型组小鼠血清IgE、IL-4水平均低于正常对照纽；IFN-γ均高于正常对照组；模型组小鼠激发后24h血清IgE、IL-4水平最高，IFN-γ水平最低（P〈0．05或P〈0．01）。结论：FI-RSV复制BALB／C小鼠哮喘模型成功可行，且24h小鼠哮喘模型较理想。     

LPAK细胞对裸鼠人胃癌的抗瘤作用

LPAK细胞(Lymphokine and PHA Activated Killer cells,LPAK)在体外实验中对Raji细胞和SGC-7901胃癌细胞均有较强的杀伤活性. LPAK细胞对裸鼠SGC-7901胃癌亦有显著的抗瘤作用,抑瘤率达84.6±8.6%.     

Production of Murine Leukemia RL♂1 Rejection Antigen Peptide pRL1a by Proteolysis of Natural Precursor pRL1b

In this study, we demonstrated that NH₂-terminal Ser and Ile residues of pRL1b (SI-pRL1a) (SIIPGLPLSL) are not involved in the recognition by RL♂1-specific cytotoxic T lymphocyte. The sensitization activity observed with pRL1b (SI-pRL1a) was not greater than that of peptides substituted with irrelevant amino acids at these positions. In serum-free medium, pRL1a retained sensitization activity, but pRL1b (SI-pRL1a) did not. Furthermore, addition of bestatin to serumcontaining medium blocked sensitization by pRL1b (SI-pRL1a). On the other hand, the addition of captopril enhanced it, probably by inhibiting the degradation of pRL1a by ACE. pRL1a-D peptide with D-Ile in place of the L-Ile residue of pRL1a (IPGLPLSL) showed sensitization, but SI-pRL1a-2,3D peptide, which has D-Iles in place of the L-Ile residues of pRL1b (SI-pRL1a), and which was not cleaved between the two D-Iles, did not. The findings suggest that pRL1a is the antigenic peptide bound to L^d molecules and pRL1b (SI-pRL1a) peptide is its natural precursor, which generates pRL1a via proteolysis.     

Impact of life-long macronutrient choice on neuroendocrine and cognitive functioning in aged mice: differential effects in stressor-reactive and stressor-resilient mouse strains

Nutrient selection emerges as a result of both genetic and environmental factors and may be further modified by stressors. The impact of this complex interrelationship on pathological outcomes is poorly understood. In the present investigation the stressor-reactive BALB/cByJ and the relatively stressor resilient C57BL/6ByJ mice were maintained on a macronutrient selection protocol or given free access to chow for 20 months. The C57BL/6ByJ mice exhibited a marked preference for fat over carbohydrates, whereas BALB/cByJ mice preferred carbohydrates over fat. Cognitive testing in a Morris water maze indicated that while BALB/cByJ mice were clearly more impaired in this task relative to their C57BL/6ByJ counterparts, there was no substantial effect of the diet at either 13 or 19 months of age. Furthermore, despite their stressor resiliency, at 19 months of age, C57BL/6ByJ mice who invariably consumed fat, exhibited greater plasma corticosterone responses to a 20-min period of restraint than chow fed animals. Indeed, the corticosterone rise was as pronounced as in the more reactive BALB/cByJ strain. Furthermore, the C57BL/6ByJ diet-fed mice showed features of insulin insensitivity and increased adiposity. These data suggest that the adverse effects of fat consumption need to be considered in the context of genetically determined vulnerability/resilience factors.     

盐酸小檗碱对葡聚糖硫酸钠所致小鼠结肠炎的作用研究

目的研究盐酸小檗碱对小鼠实验性溃疡性结肠炎的保护作用。方法实验设正常、模型、柳氮磺胺吡啶(SASP,520 mg·kg-1)和盐酸小檗碱(berberine chloride,BER)低、中、高(15 mg·kg-1、45 mg·kg-1、150 mg·kg-1)剂量组。六组小鼠自由饮用4%葡聚糖硫酸钠(dextran sulphate sodium, DSS)水溶液或蒸馏水,同时分别灌胃给予干预药物或溶剂(0·2 mL / 10 gWt,1次/ d×7 d)。以疾病活动指数(Disease activity index, DAI)评价小鼠临床症状。生化方法测定结肠组织MDA含量,SOD、MPO活性;HE染色切片,评估结肠组织病理改变;免疫组化检测ICAM-1、NF-κB p65蛋白表达水平。结果模型组DAI显著增高,结肠黏膜损伤严重;MDA含量、MPO活性及ICAM-1和NF-κB p65表达明显升高,SOD活性下降。SASP 520 mg·kg-1能明显逆转上述情况改变;BER使DAI减小,结肠黏膜损伤减轻, MDA含量、MPO活性降低,阻遏ICAM-1和NF-κB p65蛋白表达,升高SOD活性,且呈现一定剂量依赖性。结论BER可能通过抗氧自由基作用,抑制ICAM-1表达及NF-κB激活,缓解DSS所致的小鼠结肠炎症。     

吲哚美辛对荷瘤BALB/c小鼠的抗肿瘤作用

用荷S_(180)腹水肉瘤的BALB/c小鼠为动物肿瘤模型,检测其血浆中PGE_2的水平,用吲哚美辛(消炎痛,IN)肌肉注射及灌服的方法观察对S_(180)腹水肉瘤的作用。结果荷瘤小鼠血浆PGE_2为2414pg/ml,比正常对照组高1081ps/ml(P<0.05);经IN作用的荷瘤小鼠血浆PGE_2在218pg/ml以下,明显低于荷瘤对照及正常对照组(P>0.01),NK细胞杀伤活性增强,肿瘤明显小于不用药的荷瘤对照组(P<0.05)。提示PGE_2与肿瘤的发生与发展有关,IN具有抑制肿瘤生长的作用。     

Behaviour in the elevated plus-maze predicts coping after subchronic mild stress in mice

This study was aimed at investigating the coping style of mice subjected to a subchronic unpredictable mild stress procedure and its relationship to initial emotional reactivity. Two inbred strains of mice, the BALB/c ByJ and the C57BL/6 J, known to exhibit distinct emotionality, have been used. They were first observed in the elevated plus-maze and the free exploratory paradigm, each provides a separation of the population in high and low emotional mice. Half of the mice of each strain were then confronted to a 2-week subchronic unpredictable mild stress and tested for their responses in different behavioural situations (consumption of a palatable food, physical state, grooming behaviours and reactivity to a conflict situation). Mice were also tested in the light/dark procedure to assess the effect of the subchronic stress on emotional reactivity. First, a relationship between initial emotional reactivity in the elevated plus-maze and behavioural coping style in response to stress was found, high emotional mice (i.e., BALB mice) displaying inhibited behaviours and less emotional mice (i.e., BL/6 mice) exhibiting few behavioural changes. Furthermore, emotional reactivity was increased in stressed mice compared with nonstressed ones.