Abstract:[目的]糖尿病是由于多种因素和遗传因素导致体内胰岛素相对或绝对分泌不足,而引起的代谢性内分泌疾病,它以血糖、尿糖升高为特点,起病隐蔽,通过并发症使人致残致死,是继心血管、癌症之后的第三大致死性疾病,很可能成为21世纪人类的“第一杀手”(1,2)。本文采用人工诱导的方法,建立恒河猴糖尿病动物模型,研究糖尿病疾病的发展和及其并发症的发生、发展规律和防治措施,同时对于治疗糖尿病新药的安全性评价和药物疗效的观察具有广阔的运用前景。[方法]选用成熟的、健康的、雄性恒河猴9只,随机分成三个组,其中高剂量组(60mg/kg)1只,中剂量组(45m…

Abstract:[Objective] To research cold or hot constitution of four species of mouse.[Methods] eight to nine-week-old kunming mice BALB/c mice , C57BL/6Jmice , ICR mice and four to five-week-old kunming mice were inspected their biological characteristics with a simultaneous systematic inspection.The four species of mice are assessed by a same criterion about their constitution whether it is prone to cold or hot. The satime BALB/c mice treated with pill of Shenguilizhong and reserpine were used negtive control. [Results] 1. Four to five-week old kunming mice is compared with eight to nine-week-old kunming mice.The former constitution is obviously prone to hot; 2. Comparsion between BALB/c mice and C57BL/6J mice,the former is prone to cold; 3. Eight to nine-week-old male BALB/c mice and C57BL/6J mice (include male and female) are compared with eight to nine-week-old corresponding sex kunming mice respectively.Each group do not have obivious difference. Eight to nine-week-old female BALB/c mice is compared with eight to nine-week-old female kunming mice. The former is prone to cold. 4. Eight to nine-week-old ICR mice is prone to hotter than eight to nine-week-old BALB/c mice and C57BL/6J mice; The eight to nine-week-old male ICR mice is prone to hotter than the eight to nine-week-old male kunming mice.[Conclusion] The four species of mice have the difference of cold or hot constitution.

Abstract:[目的]为调查新疆野生啮齿动物的血清中嗜肝病毒的存在状态。[方法]应用乙肝表面抗原诊断试剂盒和乙肝表面抗体诊断试剂盒,对野生啮齿动物进行了血清学调查。[结果]灰旱獭(Marmotabaibaci-na)的阳性率为17.8%(24/135)、长尾黄鼠(Citellusundulatus)阳性率为17.4%(12/69)和赤颊黄鼠(Citelluserythrogenys)阳性为(8/15)。作者认为赤颊黄鼠可以作为乙型肝炎病毒潜在的动物模型。

Abstract:In our previous studies, we have infected Rhesus monkeys and Cynomolgus monkeys with SARS-CoV as the SARS model, and also, We have developed the inactivated vaccine to vaccinate Rhesus monkeys to protect them from SARS-CoV challenge. However, we wonder that the infected monkeys whether could or not be re-infected, and the acquired neutralization antibodies whether could or not play a role to protect the monkeys from SARS-CoV infection. In this study, we used four groups of monkeys, from which, the group 1 had three recovered Rhesus monkeys from SARS-CoV infection for 1 year; the group 2 had three recovered Cynomolgus monkeys from SARS-CoV infection for 1 year; the group 3 had three Rhesus monkeys that were transfused 10 ml of serum with high titer of neutralization antibody against SARS-CoV after 2 days of virus inoculation; and the group 4 had two Rhesus monkeys for SARS infecting control. the SARS-CoV strains PUMC01 isolated from patients in Beijing was used for infection.From the results of RT-PCR test, virus isolation, neutralizing antibody test, pathological examination and other lab tests and comparing with the data from SARS monkeys, we concluded that the monkeys recovered from SARS in group1 and group 2 showed strong protection from SARS-CoV challenge, the SARS-serum-transfused monkeys showed week protection from SARS-CoV challeng.

Abstract:Successful development of anti-SARS drugs and vaccines depends greatly on a reliable and sensitive animal model. In April 2003, we firstly inoculated rats, mice, rabbits and guinea-pigs, but no animals were sensitive to SARS-CoV infection. Late in May, We tried to infect 3 kinds of primates, and then Rhesus monkey(Macaca mulata) and Cynomogus Macaques (Macaca fascicularis) were found to be sensitive. Here, we report that a SARS animal model has been successfully established by inoculating SARS coronavirus into Rhesus monkeys through the nasal cavity and bronchi. We have found that although all the 8 animals show light evident clinical signs except for a transient fever 2 to 3 days after inoculation of SARS SARS-CoV, the SARS virus RNA was detected for 10-15 days using nested RT-PCR in pharyngeal swab samples in 8 cases 5 days following inoculation, the SARS coronavirus-specific IgG was detcetbale in the serum of monkeys 11-15 days after inoculation. In addition, necropsy findings of lung tissues showed typical SARS changs. Taken together, the pathological changes, immune response and virus excretion in this SARS animal model may provide insight into the mechanism of SARS infection and may greatly facilitate the screening of anti-SARS drug and vaccine evaluation.

Abstract:The bio-safety prevention and control in bio-laboratoiesis reviewed in the article.

Abstract:The standardization of envionmental safety of laborotary animal facility is one of the most important criteria for ensuring the quality of laboratory animals and animal experiments. According to safety system engineering, principles of safety management, we discussed the laboratory animal safety control, inspection, and prediction to the potential unsafety. We established a model of laboratory animal enviroment mornitoring.

Abstract:严重急性呼吸综合征是一种新近出现的严重传染性疾病,病原体为一种新的冠状病毒。但其免疫病理的发病机制尚未阐明,我们用SARS病毒感染了恒河猴和leiws大鼠,经PCR和抗体检测,证明病毒在动物体内有复制。用酶连免疫吸附试验测量动物血清中白介素(IL)-6,白介素(IL)-10,γ-干扰素(INF),肿瘤坏死因子(TNF)-α的含量。结果显示,血清中IL-10和INF-γ的含量在感染前后无显著性差异。感染后动物体内IL-6显著升高,其含量与肺部病变程度呈正相关。TNF-α的含量降低。动物模型中血清免疫因子的测定避免了临床病人由于使用抗病毒药物和激素造成的干扰,对于我们了解免疫因子在SARS免疫病理发病机制的作用有一定帮助。

Abstract:We studied the infectious effect of SARS-CoV virus on juvenile and adult Brandt's Vole (Microtus brandtii) by nasal cavity spraying method (CCID_ 50 is 105.7). SARS virus caused serious deaths in adults. The death adults showed hemorrhage from mouth, nasal cavity and intestine, hemorrhageious interstitial pneumonia and gore in liver, spleen and kidney. The survival adults showed local hemorrhagic spot in lung and emphysema, but the other organs showed no pathological abnormality. SARS virus caused no deaths in juveniles, but locomotion of infected juveniles became slower. In the early stage, there was local pneumonia in lung and SARS viruses were isolated from the pathological tissue. Only one control juvenile lived and the infected juvenile showed local pneumonia in lung. The results demonstrated that SARS-CoV infected Brandt's vole seriously and adults were more susceptive to SARS-CoV than juveniles. The Brandt's vole may be a potential animal model for SARS research.

Abstract:In order to study the relations between the immunological features and the sensitivity for pathogen in FMMU albino guinea pigs, the FMMU albino guinea pigs and pigment ones were infected with Eperythrozoon, and the immunological function were measured. The results are as follows: FMMU albino guinea pigs were more easily infected with Eperythrozoon than the pigment ones. The closed colony FMMU albino guinea pigs had its unique immunological features, its RBC immunological function was weaker than that of pigment ones. They were more easily infected with the pathogen and can be used better to be made into infected animal models than the pigment.

Abstract:[目的]探讨乙型肝炎病毒(HBV)转基因小鼠模型筛选抗HBV药物的可行性。[方法]用公认抗HBV复制药物拉米夫定对我们建立高复制HBV转基因鼠进行实验,选我们建立的1.3copy高复制HBV转基因小鼠20只,随机分成两组,每组10只。采用灌胃针灌胃法给药。对照组灌喂生理盐水,实验组灌喂拉米夫定,剂量为100mg/kg,每天2次,连续灌21d,每7d采血1次。荧光定量PCR检测血清中HBVDNA。[结果]实验组用拉米夫定前小鼠血清HBVDNA5.50±0.42(拷贝数log10数值),3周后HBVDNA已显著降低(4.63±0.57),4周后,小鼠血清HBVNDA为4.08±0.51,停药1周后,再次检测血清HBVDNA,小鼠血清HBVDNA又恢复正常水平(5.70±0.39)。[结论]我们建立的高复制HBV转基因小鼠模型验证了拉米夫定对HBV复制的抑制程度和持续时间,表明该模型可应用于抗HBV药物的筛选、评价研究。

Abstract:[目的]建立SIVp27杂交瘤细胞株,并对其分泌的SIVp27单克隆抗体进行初步鉴定。[方法]使用基因重组的SIVp27蛋白免疫BALB/c小鼠,采用杂交瘤技术使用半固体培养基法建立杂交瘤细胞株,制备单克隆抗体。通过染色体核型对杂交瘤细胞株进行鉴定;采用Westernblot、免疫荧光法、酶联免疫吸附法确定单克隆抗体的交叉反应性、相对亲和力、抗原识别表位、免疫球蛋白的类型和亚类,对单克隆抗体进行鉴定。[结果]获得四株可稳定分泌SIVp27单克隆抗体的杂交瘤细胞,1C3、2B6为IgG1类,2E12为IgG2b类,3G3为IgG2a类。四株单抗均能识别SIV的p27蛋白,与逆转录病毒SRV、STLV无交叉反应,2B6、2E12与HIVp24有交叉反应。免疫荧光法检测腹水效价为1:10240~40960。1C3、2B6、2E12、3G3染色体平均数分别为103、97、96、101。2E12与3G3识别不同的抗原表位。[结论]成功地制备出四株SIVp27单克隆抗体,均具有良好的特异性和亲和力,为进一步建立免疫分析方法,进行SIV/SAIDS及其艾滋病相关研究,奠定了基础。

Abstract:[Objective] To analyze the pathogenic mechanism of avian influenza A (H5N1) viruses in mice by investigating the changes of the immune system. [Methods] To investigate CD3+T cells, CD4+T cells, CD8+T cells by the flow cytometry. [Result] Avian influenza A(H5N1) virus destroyed the immune system, CD3+T cells, CD4+T cells, CD8+T cells declined, while the ratio of CD4+T cells/CD8+T increased, the tendency was same in blood as well as in spleen. [Conclusion] Avian influenza A(H5N1) virus can inhibit cell immunity; especially the CD8+T.

Abstract:[Objective] To observe therapeutic effect of Western medicine combined with Chinese drugs on Proteus Mirabilis diarrhea in Rhesus monkey. [Method] Sixty-three cases were randomly divided into two groups. Fourty one cases in the treatment group were treated with traditional Chinese medicine combined with antibiotic, and 22 cases in the control group were treated with antibiotic. [Results] The effective rate was 85.4% in the treatment group and 59.l% in the control group, with significant difference between the two groups (p<0.05). [Conclusion] The combined treatment of western medicine and Chinese drugs was more effective than that of simple antibiotic treatment.

Abstract:[目的]探讨乙型肝炎病毒表面抗原定位整合(p21HBsAg/HbsAg)转基因小鼠肝癌发生过程中PCNA的表达及意义。[方法]分别选取2,6,12,18,24月龄的SPF级转基因小鼠,取肝脏及肝脏肿瘤组织,进行免疫组织化学S-P法染色。[结果]①阳性肝细胞核内可见棕黄色反应颗粒;②2,6月龄转基因小鼠肝脏有少量散在分布的肝细胞呈PCNA阳性表达,阳性率分别为2.5%,3%;12月龄转基因小鼠肝脏PCNA阳性表达主要出现在非典型增生的肝细胞,阳性率23.65%;18月龄转基因小鼠发生的肝细胞癌PCNA阳性率61.68%;24月龄的转基因小鼠发生的肝细胞癌PCNA阳性率63.56%。12月龄转基因小鼠PCNA阳性率高于2,6月龄转基因小鼠(p<0.01),18月龄和24月龄的转基因小鼠PCNA阳性率高于12月龄转基因小鼠(p<0.05)。[结论]①PCNA能准确反映乙型肝炎病毒表面抗原定位整合转基因小鼠肝细胞的增殖能力,PCNA与肝细胞癌的发生、发展密切相关;②非典型增生的肝细胞有较高的PCNA阳性表达,是一群具有肿瘤增殖潜能的癌前细胞群。

Abstract:[目的]Balb/c小鼠通过尾静脉注射和鼻腔接种禽流感H5N1亚型病毒造疾病模型,观察其血细胞变化。[方法]以禽流感H5N1亚型病毒通过静脉和鼻腔接种Balb/c小鼠,分别在0~7天和0~11天取血进行血细胞计数和分类,同时对于静脉接种方法进行了0~8小时的短时间监控。[结果]静脉接种途径在接种病毒后2小时就能显著的降低小鼠的白细胞总数、粒细胞及淋巴细胞数,白细胞总数及淋巴细胞数在第3天、粒细胞数在第2天就恢复正常而后均显著升高;而鼻腔接种仅在1~3天淋巴细胞有所降低,而后恢复正常;1~6天白细胞总数及粒细胞数显著升高,而后恢复正常。[结论]从血细胞变化而言,静脉接种相比鼻腔接种方法要好。

Abstract:To understand the mechanisms of H5N1 pathogenicity, we infected 6 to 8-week-old BALB/c mice by different routes of viral inoculation. The virus caused severe disease in mice, characterized by induced hypothermia, rapid weight loss, and high mortality by 2 days postinfection. And the main clinical signs of the animals began to recover by 4 days postinfection. The most severe and widespread lesions were observed in the organs of virus-infected mice, where received the virus firstly. Only mild lesions or no lesions were observed in spleens and brains. The principal lesions were occured in 2 days postinfection. Except kidney and heart, the lesions were recovered after 4 days postinfection.

Abstract:[目的]建立具有潮霉素B(hygromycinB)抗性的3T3细胞系,用于转染目的基因(pTRE2-human-Ins)的ES阳性细胞克隆筛选的饲养层。[方法]通过脂质体转染的方法,将含有潮霉素B磷酸转移酶基因(hyg)的质粒pHyg导入NIH3T3细胞中,利用潮霉素B的药物选择特性,对转染细胞进行压力筛选,并对其进行PCR和southernblot鉴定。[结果]经300ug/ml的潮霉素B压力筛选后,获得了抗性细胞克隆。抗性NIH3T3细胞的形态和生长速度与正常NIH3T3细胞没有差异,特异性核苷酸引物检测抗性细胞基因组DNA,可以扩增出相应的核苷酸片段,Southernblot鉴定结果表明潮霉素基因片段已整合入潮霉素抗性NIH3T3细胞。[结论]本实验通过脂质体介导的方法成功地培育了潮霉素B抗性的NIH3T3细胞,为进行目的基因(pTRE2-human-Ins)转染ES细胞的阳性细胞克隆筛选打下了基础。

Abstract:[Objective] The present work is to establish rat spontaneous mammary adenocarcinoma tumor strain to produce the type C oncovirus and investigate the pathological characteristics of rat spontaneous mammary adenocarcinomas caused by type C oncovirus. Methods: The tumor strain of rat mammary adenocarcinomas was established by alternate descent generations of carcinoma struma and cell suspension. For pathological observation, rat mammary primary adenocarcinoma and implant adenocarcinoma were respectively fixed in 10% formaline, embedded in paraffins, routinely stained with HE and Ag. For electron microscope observation, rat mammary primary carcinoma and implant carcinoma were double fixed in 2.5% glutaraldehyde and 1% osmic acid respectively, embedded in Epon 812, ultrathin sectioned, double stained with uranium acetate and lead citrate, and observed under transmission electron microscope (TEM). [Results] The volume of rat mammary primary carcinoma cells is quite small, only 10 (m in diameter. The typical tubular structures are found to be in such shapes as of globe, pappila, tortuousribbon and whorl. The carcinoma cells are separated into irregular nest structure by the reticular fibres after Ag staining. The above-mentioned shows that, as a type of rat mammary epithelial anaplastic adenocarcinomas, rat mammary carcinoma is originated from epithelial tissues. The implant carcinoma cells are round, cubic, and polygonal in shape, and carcinoma gigantic cells, pale cells and the like appeared, which are arranged in such structures as of nest, layer, trabecula, pappila, glomerate, adenocarcinoma tubule, and space, with heteomorphosis notable. The carcinoma cells are irregular in size, with large nuclei and increased nucleolus. Besides, there are bundles of tension protofibril in cytoplasm and seldom seen secretory granules. Among the cells there are primary gland cavities and the desmosome. The type C oncovirus particles are discovered among the carcinoma cells and in their cytoplasm, which are 100nm in diameter, in the shape of globe and with external envelopes endomembranes and central cores. [Conclusion] This is the first time that rat spontaneous mammary adenocarcinomas have been established to generate type C oncovirus tumor strain. It makes up a type of rat mammary epithelial anaplastic adenocarcinomas. And its pathological morphology is of polymorphosm.

Abstract:To investigate the pathogenicity of avian influenza virus in Gerbil Anesthetized gerbils were inoculated with avian influenza virus in biosafety level 3 laboratory. Fourteen days after inoculation,clinical signs were observed and the blood samples were collected to analyze abti-AIV antibody. Tissue samples from lungs, livers, and kidneys were used to virus isolation and histopathology. Result showed that the H5N1 AIV caused severe disease in gerbils mainly between day 2.p.i ang 6.p.i, which characterized by ruffled fur, inappetence, hunched-back posture, labored breathing, hypothermia, weight loss. The death rate was 44%. Antibody was detectable from day 10. P.I. The histopathologic examinations showed variable degrees of lesions including congestion and hemorrhage in lungs, livers, kidneys. The lesions of the lungs showed interstitial pneumonia, dropsy and configuration breakage.

Abstract:[目的]建立禽流感H5N1病毒感染恒河猴的动物模型,探讨禽流感在哺乳类动物的发病机制。[方法]通过“环甲膜穿刺术”经气管注射鸡胚培养的禽流感H5N1病毒(AF148678;ACGoose/Guangdong/11961H5N1)感染恒河猴,观察恒河猴染毒后出现的临床体征,用显微计数法检测外周血白细胞的动态变化,用ELISA检测禽流感病毒特异性抗体变化规律,用流式细胞仪检测外周血T淋巴细胞及其亚群的动态变化。在染毒后第1天、第3天、第10天和第14天分别剖杀染毒组恒河猴1只,HE染色观察主要组织器官的病理变化,用病毒分离、免疫组化和RT-PCR三种方法分析禽流感病毒侵袭机体的特点。[结果]临床症状和体征:急性起病,表现为发热,呼吸困难,精神状态下降,活动度明显减少,食欲下降,咳嗽,紫绀等,肺部听诊双肺可闻及干、湿音。1、病理特点:以肺部损伤为主,伴多器官病变。肺部的病变主要表现为弥漫性肺泡损伤,先后经历渗出期、增生期和纤维化期;在肝脏、肾脏和中枢神经系统中也观察到变性、坏死等病理变化。2、病毒侵袭机体的特点:病毒只在呼吸系统中复制,不在呼吸道以外的组织器官中复制;肺内支气管上皮细胞、肺泡上皮细胞和肺巨噬细胞是禽流感病毒侵犯的主要细胞类型。3、外周血象特点:外周血白细胞总数、淋巴细胞数出现短暂的下降,中性粒细胞数先升后降,但均于感染第7天后逐渐恢复到正常水平。4、抗体变化特点:感染后第7~11天,抗体水平持续快速升高;感染第11天后,抗体水平呈逐渐缓慢升高趋势(观察到染毒后50天为止)。5、细胞免疫特点:细胞免疫功能受损,表现为CD3+T淋巴细、CD3+CD4+T淋巴细胞和CD3+CD8+T淋巴细胞均出现短暂的下降,但这种细胞免疫功能受损是可逆的,到感染第7天后逐渐恢复回升至正常。[结论]1、恒河猴感染后的临床特点、病理变化、外周血象、免疫反应等均与人禽流感严重病例相类似,表明该模型是成功的,可为禽流感病毒在人体内致病机理的研究以及抗禽流感病毒的药物和疫苗评价提供最近似于人类的动物模型。2、综合本研究的实验结果,我们认为,H5N1禽流感毒主要攻击的对象为呼吸系统,不在呼吸道以外的组织器官中复制。禽流感病毒感染引起的急性弥漫性肺损伤是发病的中心环节,其发病可能经过病毒侵入、复制阶段,免疫损伤阶段和多器官功能损伤阶段。

Abstract:本研究利用11个微卫星位点,对海南和广西恒河猴进行了遗传检测,并通过POPGEN32软件计算各个微卫星座位的等位基因频率、有效等位基因数目(Ne)、多态信息含量(PIC)和遗传杂合度(H)。结果表明,所选择的11个微卫星位点均存在高度的遗传多态性,H为0.6848~0.河河猴的Ne、PIC和H的平均值均高于海南猴,分别为4.2583、0.7090、0.7706和4.2054、0.7025、0.7656,这种差别可能与地域来源有关。这些研究为微卫星标记分析恒河猴遗传多样性提供理论基础。

Abstract:Objective to investigate the infection status of STLV-1 in Macaca mulatta so as to decrease the infection ratio of STLV-1 effectively. Method:Monkey sera were tested with STLV-1 ELISA. Results 103 sera were STLV-1 antibody positive, and 19 sera were STLV-1 antibody equivocal, the others were STLV-1 antibody negative in 2455 sera sent to BioReliance Co. for STLV-1 antibody test. Conclusion STLV-1 average infection ratio in Macaca mulatta is 4.97%, of which, that in cynomolgus monkey is 5.4%, twice of that in rhesus monkey, STLV-1 infection ratio in Macaca mulatta increases with age.

Abstract:[Objective] To evaluate whether the combination of an antiprogestin (mifepristone) +aromatase inhibitors (letrozole or aminoglutethimide) or an iNOS inhibitor (aminoguandine) are effective in ending pregnancy during early gestation in rhesus monkeys. [Methods] The 30 pregnant monkeys were be randomly assigned five groups (treatment group:6 animals per group, but for 6 animals in control group) and to be undergone treatment with control group : Placebo (1ml/animal,), group A: Mifepristone (1mg/kg, sc.,), group B: Mifepristone(sc.) + Letrozole(2.5mg/animals, sc. ), group C: Mifepristone(1mg/kg,sc.) + aminoglutethimide(50mg/kg sc., bid,) and group D: Mifepristone(1mg/kg,sc.) + aminoguanidine(150mg/kg, sc., bid,) on d30, 31, and 32 of gestation. all the pregnant monkeys were be identified by ultrasound instrument on d29 of gestation. [Results] These results shown that 6/6 the animals in group B, C and D were effectively terminate the early pregnancy, the 3/6 animals in group A were be terminated pregnancy, and the 2/8 animals in control group were be terminated after treatment, and these combinations could also result in effective evacuation of the uterine cavity and reduce bleeding. [Conclusion] The paper suggested that the treatment will effectively terminate the early pregnancy in rhesus monkeys, the combination of agents used was likely to be more effective than the therapy in women and could reduce the long duration of bleeding associated with the present treatment, and might replace present therapy for medical abortion.

Abstract:The SARS is a emerging infectious disease which was conformed in china firstly and spread over 37 countries and regions. Three SARS CoV animal models with Rhesus macaque, Lewis rat and Microtus brandtii were established in Institute of Laboratory Animal Science, CAMS and PUMC , China. In current paper, those SARS-CoV animal models were compared on pathological changes, immuno- response and the replication of SARS- CoV in vivo. 8 Rhesus macaques, 20 Microtus brandtii and 9 Lewis rats were infected with SARS-CoV through the nasal cavity, and sacrificed for collecting pathologic tissues on different day after inoculation. Similar pathological changes were observed in SARS CoV infected Rhesus macaques, Lewis rats and Microtus brandtii and the pathological changes was similar with SARS case of human. The SARS-CoV was carried and replicated in Rhesus macaques and last longer than Lewis rats. The infected Microtus brandtii carried SARS-CoV, but the replication of the virus was not detected by isolation and culture of the virus on Vero-E6 cell. The SARS-CoV specific IgG was detected in both of rhesus macaques and Lewis rats( The detective agents was not available for IgG of Microtus brandtii). It is interesting that SARS-CoV caused Microtus brandtii death at a rate of 10%, which is similar to the mortality of SARS on human. ON summary, the Rhesus macaques model is one of the ideal animal model to study SARS-CoV replication and vaccine and the Microtus brandtii can be used to study the lethality of SARS-CoV.

Abstract:To study the pathology of H5N1 avian influenza virus, H5N1 avian influenza virus was inoculated the tail intravenous to the BALB/c male mice and the mice were infected and died. With 1-3 days, the mice began to show acute respiratory distress, decreased activity, less food and water intake, weight and temperature declined. The death of the mice was occured in 2-3days. From 4 to 7 days, the clinical symptom of the mice was resumed. The infected mice showed lung hemorrhage, epicardium and liver necrosis. In histopathology, the main lesion was consolidated pulmonary tissue. The lumina of alveoli and bronchioles were variably filled with protein-rich edema, fluid, fibrin, erythrocytes and cell debris. Extrarespiratory lesions also were found in the mice. There were accumulation of lymphocytes in the epicardium and the liver. Up to the present the epicardium lesion and the hepatic lesion have not been reported in the H5N1 infected mice. The virus titers were not detected in the heart, liver, spleen, kidney and brain tissues by inoculated into embryonated hens' eggs. The virus antigens were not detected by immunohistochemistry in the 6 organ tissues. Our results suggested that the many organ tissues necrosis in the H5N1 virus infected mice might be caused by more cytokine responses, as result multiple-organ dysfunction syndrome, not caused by the virus replication in the organ tissues.

Abstract:The establishment of Severe Acute Respiratory Syndrome(SARS) animal models by SARS-Coronavirus (SARS-CoV) infection can promote the study of SARS etiology, pathogenesis, laboratory diagnosis, anti-SARS coronavirus (SARS-CoV) drug screening, development of vaccines, and more detailed description of SARS. That is to say, SARS-CoV infection animal model is the key-point of the study on SARS and will take an important role throughout of SARS research. There are at least four kind of non-human primates (Rhesus, Cynomolgus, African Green, and Common Marmosets) and six kind of small animal models (rat, mice, Guinea Pigs, hamster, Brandt's vole, Transgenic or Knock out), ferret and domestic cat were reported by today. Some of them have been broadly used on the evaluation of safety and efficiency of vaccines and drugs, such as BALB/c mice. Here, we reviewed the report on SARS animal models and compared them with SRAS patients. Thereafter, we concluded some technical guidelines for the establishment of SARS animal model.

Abstract:Severe Acute Respiratory Syndrome (SARS) is an emerging infectious disease by the pathogen of a novel coronavirus (SARS-CoV), which characterized by rapid progress, high prevalence and fatality. Among the 23 infected countries, China is the most severely affected area. Chinese scientists had done enormous works on epidemiology, etiology, pathology, animal model and vaccines, and achieved plentiful and substantial results, especially in tracing source of SARS-CoV, therapeutics combining with traditional Chinese medicine (TCM) and west medicine, pathogenesis, SARS-CoV inactivated vaccine and rhesus animal models. In these research areas, the Chinese scientists are putting the world ahead in SARS research. In this paper, we reviewed the achievements on SARS in China.

Abstract:Presenilin1(PS1)的突变是早发家族性老年痴呆发生的重要因素之一。目前对于PS1结构和功能的研究表明,PS1作为一种多次跨膜并具有γ-secretase活性的蛋白酶,很可能参与众多的细胞信号传导通路,影响细胞分化和调亡、组织及个体的发育等等。但对于PS1的精细结构和功能目前了解甚少,为探讨PS1的精细结构和功能,本研究构建了鼠PS1-GFP融合蛋白表达载体。方法:我们设计了扩增PS1的cDNA全长的引物,以C57BL/6小鼠9天胚的RNA为模板,利用RT-PCR的方法从C57BL/6小鼠9天胚中获得PS1的cDNA,经测序确认后,将其克隆到pMD18-TVector中。设计引物:上游5’-GCCGAATTCTATGACAGAGATACCTGCACC-3’;下游5’-GAAGGATCCGATATAAAACTGATGGAATGC-3’,上游含有EcoRI酶切位点,下游含有BamHI酶切位点。利用高保真DNA聚合酶通过PCR方法将pMD18-T-PS1质粒中的PS1基因亚克隆到pEGFP-C1载体中,获得pEGFP-C1-PS1融合蛋白表达载体,然后利用EcoRI和BamHI从pEGFP-C1-PS1融合蛋白中切下PS1基因,从pMD18-T-PS1质粒中切下载体部分,经过连接,获得中间载体,利用该重组载体中的EcoRI和SalI酶切位点,酶切连接入pEGFP-N2载体中,获得pEGFP-N2-PS1融合蛋白表达载体,经测序鉴定后备用。

Abstract:[Objectives] To establish a PCR method to detect SV5 in biological material from monkeys. [Methods] We have designed a pair of primers matched with SH gene of SV5 for PCR and sequenced the product fragments with BLAST soft to identify the homology and conformed by with AccIII restriction digestion. we also designed nested primers to improve the sensitivity of the PCR. The PCR technique was used to detect our cells and sera from Rhesus monkeys. [Results] The PCR product was proved to be the frangment of the SH gene of SV5, and the PCR product was digested with the AccIII which is a specific site of the gene fragment. The sensibility of the examination was improved by nested PCR. All samples from monkeys were detected to be negative using this PCR method. [Conclusions] We established the PCR method to detect SV5.

Abstract:[目的]人工感染法建立包虫病动物模型。[方法]将藏羊源细粒棘球绦虫原头蚴悬液1ml(每ml悬液含4000个原头蚴,青霉素1000U,链霉素1000U)注射于50只(25♂♂25♀♀)4周龄ICR小鼠腹腔内,每周测体重与腰围1次;设空白对照组10只(5♂♂5♀♀)。[结果]接种第20天后,动物体重和腰围均高于空白对照组的各项指标;第90天剖检动物,包囊生成率为96%(48/50),人工感染成功率为96%。[结论]绵羊源性细粒棘球绦虫原头蚴悬液腹腔注射ICR小鼠建立包虫病动物模型的方法可为包虫病的防制研究工作提供简便、可靠和实用的实验动物模型。

Abstract:[Objective] To observe the pathological changes in the livers of p21 HBsAg/HBsAg transgenic mice. [Methods] The p21 HBsAg/HBsAg transgenic mice(2,6,12, 18, 24 months) in SPF grade and corresponding p21 +/+ mice were dissected and the liver and hepatic tumor tissues were extirpated for the examination by histological HE staining and electron microscopy. [Results] Distinct pathological changes appeared in the liver of p21 HBsAg/HBsAg transgenic mice both macroscopically and microscopically. With the increase on age, the liver of the transgenic mice turned to be dark and sclerotic with scattered formation of nodules and tumors. Under light microscope, the liver cells were swollen and inflammatory cell infiltration occurred. Fatty degeneration appeared with punctuate, focal and crumblike necrosis. Atypical hyperplasia and hepatocellular carcinoma (HCC) developed. Resembling normal hepatocytes, hepatpocarcinoma cells were well differentiated, forming cord-like and acinar-like structures. The nuclei of carcinoma cells are dark stained with karyokinetic figures and aberrated with invagination of nuclear membrane under electron microscope. Mitochondria distended, manifolded and the ridges reduced. HCC were found in four cases of 18 months old p21 HBsAg/HBsAg transgenic mice (4/10, 40%), and six cases of 24 months (6/10,60% ) respectively, of which metastasis occurred in two cases. [Conclusions] Obviously pathogenic changes occurred in the liver of p21 HBsAg/HBsAg transgenic mice. Well differentiated hepatocarcinoma became to arise in the mice at the age of 18 months. Metastasis of HCCs would happen in elderly transgenic mice.