人工饲养条件下死亡实验恒河猴肠道病理改变特点分析

目的观察人工饲养条件下实验恒河猴肠道病理改变,探讨实验猴肠道疾病分布规律和病理改变特点,丰富实验猴自发病变基本研究资料。方法对1998-2008年云南地区饲养的自然死亡的155只恒河猴（年龄2-20岁）的肠道进行病理检查,按年龄分为幼年组、成年组、老年组,并对观察结果进行统计学分析。结果155例恒河猴中58例检出肠道病变,有慢性肠炎、急性肠炎、黏膜充血水肿、出血、糜烂、溃疡、穿孔、寄生虫共8种主要病变,出现率最高的为急性肠炎（20．00％）。实验猴不同年龄组肠道病变类型分布基本相同,肠道病变率随年龄增长而增高,不同年龄组间统计学分析差异无显著性。结论人工饲养条件下死亡实验猴肠道病变检出率较高,急性肠炎是实验猴的主要致死原因之一,实验猴肠道病理改变随年龄增长而病变加重。对实验猴饲养和研究时,应重视肠道病变因素,尤其是急性肠炎。死亡实验猴肠道病变研究对实验猴的质量控制和相关动物实验有重要指导价值。     

人工饲养条件下死亡恒河猴肺脏病理改变分析

目的观察人工饲养条件下实验恒河猴肺脏病理改变,探讨实验猴呼吸系统疾病分布规律和病理改变特点,丰富实验猴自发病变基本研究资料。方法对1998～2008年云南地区饲养的自然死亡的155只恒河猴（年龄2～20岁）的肺脏进行病理检查,按年龄分为幼年组、成年组、老年组,并对观察结果进行统计学分析。结果实验猴肺脏主要病变有大叶性肺炎、支气管肺炎、间质性肺炎、肺气肿、支气管扩张症、胸膜炎、肺肉芽肿性炎等12种,出现率最高的为支气管肺炎（18.71%）和大叶性肺炎（16.74%）。恒河猴肺脏病变在不同年龄阶段均有发生,老年猴组肺脏病变发生率最高,疾病类型和发生率在不同年组中分布不相同,统计学分析显示：支气管炎病变成年组发病率明显高于幼年组;肺气肿病变老年组明显高于成年组和幼年组,（P〈0.05）。结论人工饲养条件下死亡实验猴肺脏病变检出率较高,实验猴肺脏病变在不同年龄阶段存在差异,实验猴肺脏病理改变结果丰富了实验猴的基本研究资料,对实验猴的质量控制和相关动物实验有重要价值。     

实验动物恒河猴朊病毒基因分析

目的　通过对拟应用于航天飞船模拟试验的实验动物恒河猴进行朊病毒基因检测和分析 ,了解其朊病毒疾病易感性 ,进而为该试验所用实验动物质量提供朊病毒疾病的遗传数据。方法　根据已报道的猴朊病毒基因序列设计引物对 ,采用PCR方法扩增恒河猴朊病毒基因 ,将其克隆到T—VECTOR ,序列测定及分析。结果　序列测定及分析表明所克隆的恒河猴PRNP基因片段为 76 2bp ,该基因内无内含子 ,包含了PRNP完整编码区序列 ,编码 2 5 3个氨基酸的前体蛋白 ,推测其相对分子质量约 2 7 6× 10 3。与已报道的猴的相应序列作比较 ,核苷酸序列同源性分别为 95 %以上 ,其编码的氨基酸同源性均为 95 %以上。其中发现了已报道的多态性位点N97S ,H10 0N和未曾见报道的Q5 2E点突变位点 ,以及沉默突变位点A78G ,T84C ,T4 95C ,A5 6 4G ,C6 5 4 ,未发现与朊病毒敏感性连锁的氨基酸多态位点P10 2L、M12 9V ,N171S和E2 19K。结论　航天医学实验所用 17只恒河猴不存在朊病毒敏感性基因。     

单克隆抗体治疗日本脑炎病毒感染恒河猴的实验研究

感染日本脑炎病毒(JEV)的恒河猴,出现脑炎的一系列症状与体征,终因呼吸及循环衰竭而死亡。JEV感染猴体温升到超过39℃以上后的第2天,注射单克隆抗体(McAb)制剂进行实验性治疗。结果显示,McAb经肌肉、静脉、硬脑膜下加肌肉等不同途径注射后,均有良好的疗效,对恒河猴的保护率达100％,其中以硬膜下加肌肉途径注射McAb的效果最佳。多次注射McAb,未发现任何不良反应与毒副作用。本研究表明,将鼠源性McAb用于灵长类安全可靠,若过渡到临床使用,是可行的。     

实验恒河猴超声心动图的初步研究

分别采用二维、脉冲多普勒及M型超声心动图Teichholtz公式对1 0只健康成年实验恒河猴(Macacamulatta)的心脏结构、心脏血流动力学及左室收缩功能进行测定,并比较不同性别间各参数的差异,以建立正常健康成年恒河猴超声心动图相关生理学参数的基础正常值。结果表明,健康成年实验恒河猴超声心动图各项生理指标类似于人类新生儿的指标,雌、雄组间比较除室间隔舒张末期厚度有统计学差异外(P <0 0 5 ) ,其余指标均无统计学差异(P >0 0 5 )。     

STZ诱发实验恒河猴糖尿病性视网膜并发症模型的建立

目的　建立糖尿病性视网膜并发症 (DiabeticRetinopathy ,DR)动物模型。方法　本研究选用 4只健康成熟的雄性恒河猴分别以剂量为 6 0mg kg、4 5mg kg静脉一次注射及 30mg kg静脉二次注射 (中间间隔 15d)链脲佐菌素 (Streptozotocin ,STZ)。结果　使用不同剂量的STZ注射恒河猴 ,分别造成了胰岛素依赖性糖尿病 (InsulinDepen dentDiabetesMellitus ,IDDM)及慢性持续性高血糖症 (StateofChronicHyperglycemia,SCH)两种类型的模型 ,从而诱导出不同程度的DR。眼底荧光造影结果显示∶用药后 6 3～ 91d4只实验猴均出现不同程度的视网膜病 ,分别显示早期眼底微血管动脉扩张 ,视网膜出血瘤 ,微血管瘤及新生血管、晚期白内障等。结论　本研究所建立的糖尿病性视网膜并发症模型 ,对于进一步研究糖尿病及其并发症的发病机理 ,筛选及开发治疗糖尿病性视网膜病的新药及药物安全性评价将会具有广阔的应用前景     

戊型肝炎病毒实验感染恒河猴的研究

报道了用戊型肝炎(Hepatitis E, HE)病人粪便悬液感染恒河猴后的组织病理学、血液生化与免疫学以及病毒学分子生物学检测的结果.三只实验猴在感染后第3～4周均出现ALT异常;粪便以及肝脏与胆囊组织超薄切片中电镜观察到27～34nm大小的病毒样颗粒;病理组织切片观察表明,肝脏组织有典型的急性炎症病灶;粪便与血清经RT-nPCR扩增到戊型肝炎病毒(Hepatitis E Virus, HEV)特异性片段,粪便排毒从感染后第7天持续至第50天左右,病毒血症迟于粪便排毒,出现于感染后两周左右,维持1～2周;ELISA检测发现,实验猴血清中HEV IgG抗体水平在感染后3～4周阳转,4～5个月后转阴.这些实验结果提示,恒河猴作为HEV感染实验动物模型是理想的,建立系统的恒河猴实验模型对探讨HEV感染发病机理、机体免疫应答以及临床诊断与疫苗研制具有重要意义.     

戊型肝炎病毒实验感染恒河猴的研究

报道了用戊型肝炎（ＨｅｐａｔｉｔｉｓＥ,ＨＥ）病人粪便悬液感染恒河猴后的组织病理学、血液生化与免疫学以及病毒学分子生物学检测的结果。三只实验猴在感染后第３～４周均出现ＡＬＴ异常;粪便以及肝脏与胆囊组织超薄切片中电镜观察到２７～３４ｎｍ大小的病毒样颗粒;病理组织切片观察表明,肝脏组织有典型的急性炎症病灶;粪便与血清经ＲＴｎＰＣＲ扩增到戊型肝炎病毒（ＨｅｐａｔｉｔｉｓＥＶｉｒｕｓ,ＨＥＶ）特异性片段,粪便排毒从感染后第７天持续至第５０天左右,病毒血症迟于粪便排毒,出现于感染后两周左右,维持１～２周;ＥＬＩＳＡ检测发现,实验猴血清中ＨＥＶＩｇＧ抗体水平在感染后３～４周阳转,４～５个月后转阴。这些实验结果提示,恒河猴作为ＨＥＶ感染实验动物模型是理想的,建立系统的恒河猴实验模型对探讨ＨＥＶ感染发病机理、机体免疫应答以及临床诊断与疫苗研制具有重要意义。     

人工繁育恒河猴婴猴生长发育指标的测定分析

目的建立人工繁殖恒河猴婴猴生长发育指标的标准数据库。方法随机对90只人工饲养繁殖的恒河猴（从100d至1周岁）进行体重、身长、尾长、前肢长、后肢长发育指标测定。结果测定后的数据,经统计学分析和绘制生长曲线图,发现人工饲养条件下的恒河猴（1周岁前）,其生长发育指标基本均匀一致,只有个别出现发育迟缓或发育不良现象。随时间推移,雄性生长速度要快于雌性。结论所建立的恒河猴婴猴正常生长发育生理指标,为提高人工饲养繁育恒河猴技术和不断改善恒河猴营养与发育健康提供了科学数据。     

The distribution pattern of rhesus and Assamese monkeys in Nepal

Surveys of the distribution and some ecological characteristics of rhesus monkeys (Macaca mulatta) and Assamese monkeys (M. assamensis) in Nepal were conducted during 234 days in 1976, 1978, and 1984. Rhesus monkeys dominated in the tropical, subtropical, and temperate forests below 3,000 m a.s.l. all over Nepal. Assamese monkeys were patchily distributed along rivers in the tropical and subtropical areas. Both species principally utilized forests parapatrically. The mean troop size of rhesus monkeys (29.5) was significantly larger than that of Assamese monkeys (19.1). Discontinuous distribution of Assamese monkeys probably appeared as a result of the expansion of rhesus monkey distribution in the mid- and late-Pleistocene. Because of small distribution areas and small numbers of monkeys, urgent conservation policy must be pursued.     

Menopause in female rhesus monkeys

Fifteen female rhesus monkeys (Macaca mulatto), ranging in age from 8 to 34 years, were studied for one year to characterize the endocrine and menstrual changes associated with menopause in this species. Five monkeys were premenopausal; these younger monkeys, ages 8–11 years, menstruated and showed cyclic ovarian activity during the 12–month study period, as evidenced by menses and periodic elevations of serum estradiol (E₂) and luteinizing hormone (LH) concentrations. Four females, ages 24–26 years, were in transition to menopause. Two of these perimenopausal females menstruated and secreted E₂ and LH in a periodic fashion; the other two females showed elevated LH concentrations, consistently low E₂ levels, and no evidence of menstruation. Six females, ages 27–34 years, were clearly postmenopausal; LH concentrations were high, whereas E₂ concentrations were uniformly low. There was a significant inverse correlation between basal E₂ concentrations and age, and a significant positive correlation between age and LH concentrations across all 15 animals. Hormonal changes indicative of ovulation, when they occurred, were generally restricted to the winter and early spring months. Histological analysis of ovaries from four postmenopausal females revealed little or no evidence of active folliculogenesis. These data indicate that menopause in female rhesus monkeys does not occur until the second half of thethird decade of life. © 1995 Wiley-Liss, Inc.     

Delay discounting of saccharin in rhesus monkeys

The value of a reinforcer decreases as the time until its receipt increases, a phenomenon referred to as delay discounting. Although delay discounting of non-drug reinforcers has been studied extensively in a number of species, our knowledge of discounting in non-human primates is limited. In the present study, rhesus monkeys were allowed to choose in discrete trials between 0.05% saccharin delivered in different amounts and with different delays. Indifference points were calculated and discounting functions were established. Discounting functions for saccharin were well described by a hyperbolic function. Moreover, the discounting rates for saccharin in all six monkeys were comparable to those of other non-human animals responding for non-drug reinforcers. Also consistent with other studies of non-human animals, changing the amount of a saccharin reinforcer available after a 10-s delay did not affect its relative subjective value. Discounting functions for saccharin were steeper than we found in a previous study with cocaine, raising the possibility that drugs such as cocaine may be discounted less steeply than non-drug reinforcers.     

Isolation,identification of Streptococcus pneumoniae from infected rhesus monkeys and control efficacy

Background Streptococcus pneumoniae can cause a wide variety of illnesses. Primate animals can be infected by the pneumococcus. A disease occurred among rhesus monkeys in winter 2006. Methods Routine clinical observation, necropsies, bacteriological examinations were conducted, and PCR, pathogenicity to BALB/c mice and antibiotic susceptibility test were examined additionally. Results We conclude that the agent is S. pneumoniae. Based on the antibiotic susceptibility test, a dose of 20 mg/kg body weight daily of Erythromycin was given intramuscular injection for 5 days, resulting in the disappearance of clinical signs, and no newly case reappear be observed till today. Conclusions Therefore, it is suggested that the outbreak of respiratory disease in the rhesus monkeys was because of transmission of S. pneumoniae among rhesus monkeys. The antibiotic therapy finding underscores the utility of Erythromycin to cure the infected rhesus monkeys without causing side effects and without contributing to the further development of antibiotic resistance.     

Species discrimination and concept formation by rhesus monkeys (Macaca mulatta)

There are 19 species in genusMacaca and some of them are living in sympatry (Fooden, 1980). Although inter-specific hybrids are relatively easy to produce under artificial conditions, hybridization does not occur naturally. What is preventing that among the species of genusMacaca? Three rhesus monkeys acquired a discrimination between pictures with rhesus monkeys and without rhesus monkeys. All subjects showed positive transfer of this discrimination to new pictures with rhesus monkeys and without rhesus monkeys. A further test showed that these monkeys could discriminate between pictures of rhesus monkeys and pictures of Japanese monkeys. The results suggest that rhesus monkeys recognize rhesus monkeys as a class, independent of the actual stimuli such as a picture or an individual monkey. The ability to recognize members of their own species and the opportunities for such learning may be an important factor preventing hybridization among the species of genusMacaca.     

Frequency of mast cells in the olfactory mucosa of rhesus monkeys

During studies of the olfactory mucosa and its response to the different levels of circulating sex hormones, considerable numbers of mast cells have been observed in its epithelia and subepithelial regions. The number of these cells in the olfactory mucosa of male monkeys differs greatly from that found in females. The frequency of these cells in the olfactory mucosa of females fluctuates significantly during the menstrual cycle. These fluctations stimultaneously correspond to the well known changes in olfactory sensitivity: around ovulation, when the olfactory sensitivity for certain odorants is high, the number of mast cells in the olfactory mucosa also increases.     

Correlation of zona-binding with oocyte maturation and sperm motility in rhesus monkeys by hemizona assay

The hemizona assay (HZA) in Rhesus monkeys was employed to study the correlation of zona-binding ability with sperm motility or with naturally developing oocytes at various maturational stages. Oocytes from unstimulated ovaries were retrieved within 2 hr from monkeys sacrificed for vaccine production (in reproductive season, but with their menstrual cycles not determined). Oocytes were divided into four groups based on their morphological maturation: 1) Oocytes surrounded by more than one cumulus layer (MC); 2) Oocytes retaining intact germinal vesicle nuclei (GV); 3) Oocytes with germinal vesicle breakdown showing distinct perivitelline space (PVS); and 4) Oocytes extruding the first polar body (PBI). The mean numbers of sperm bound to hemizona for PB1, PVS, GV, and MC groups were 132.9 ± 12.0, 71.5 ± 10.1, 36.1 ± 4.0, and 20.1 ± 2.9 (Mean ± SE), respectively. The four groups showed significant differences from each other in sperm/egg binding ability (P < 0.01). The number of bound sperm significantly increased with oocyte maturation. The present study also showed that zona-binding ability was also affected by sperm motility. For sperm with 67.7% motility and sperm with 31.2% motility, the average numbers of bound sperm were 43.5 ± 2.2 and 25.3 ± 2.9 (Mean ± SE), respectively. There was significantly higher binding ability for sperm with higher motility (P < 0.01). The results suggest that: 1) The rhesus monkey model can serve as a very sensitive model for studying sperm/egg interaction by HZA; 2) Sperm motility positively correlated with sperm/egg binding; and 3) Sperm/egg binding ability increases with oocyte maturation. The binding ability is highest when oocytes matured to the PB1 stage, which is also the best opportunity for fertilization. This is strong evidence for the “zona maturation” hypothesis. © 1994 Wiley-Liss, Inc.     

Dynamic changes in ovarian follicles measured by ultrasonography during gonadotropin stimulation in rhesus monkeys

The objective was to study dynamic changes of ovaries in rhesus macaques stimulated by gonadotropins to identify an indicator for predicting ovarian response to stimulation. Twenty-one cycling monkeys were given 36 IU/d recombinant human follicle-stimulating hormone (rhFSH) for 8 d. Animals (n = 17) with ≥5 follicles (≥3 mm) in their ovaries on Day 9 of ovarian stimulation were deemed good responders, whereas those with a lesser response were poor responders (n = 4). For these two groups, the mean (±SD) numbers of oocytes retrieved were 44.3 ± 21.4 and 11.0 ± 4.6, respectively. In retrospect, the mean diameters of the ovaries and of the largest follicles, the total number of detectable follicles (diameter >0.5 mm), and serum estradiol concentrations gradually increased during the stimulation period in the good responders but did not increase in the poor responders. Comparing good and poor responders, the number of ovarian follicles >0.5 mm already exhibited a difference (12.9 ± 6.5 vs. 2.9 ± 1.3, respectively, P < 0.05) on Day 1 of stimulation. However, for other end points, differences were not significant until at least Day 5. Moreover, good responders yielded a fivefold higher blastocyst development rate than that of poor responders (P < 0.01). In conclusion, the number of ovarian follicles detected with ultrasonography could be useful to predict the response to FSH stimulation in non-human primates.