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。     

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。     

人工饲养条件下恒河猴血液学、血液生化正常参考值测定及分析

目的测定人工饲养条件下104只健康恒河猴的血液学、血液生化正常参考值,并分析不同性别、不同年龄阶段(青幼年组∶3～4岁,成年组∶5～10岁,老年组∶11～25岁)恒河猴的血液学、血液生化值的差异及相互关系.方法应用全自动血液细胞分析仪和全自动血液生化分析仪,测定及分析非麻醉状态下健康恒河猴血液学和血液生化正常值.结果血液学值中较明显低 (P<0.05) 的项目为MED.血液生化值中♀猴比♂猴明显低 (P<0.01)的项目有ALT、ALP、GGT、CHOL、APOA、HDL、LDL、P3+、BUN,较明显低 (P<0.05) 的项目为ALB.较明显高 (P<0.05) 的项目为UA.各年龄组之间的分析如下:血液学值中RDW值为青幼年组比成年组及老年组均明显低(P<0.01),MEDIAN值为成年组比青幼年组较明显高 (P<0.05),血液生化值中青幼年组比成年组及老年组均明显高 (P<0.01)的项目有ALT、ALP、GGT、P3+,青幼年组比成年组明显高(P<0.01)的项目为BUN、ALP、AST、,青幼年组比老年组明显高(P<0.01)的项目为CK、TF;成年组比老年组明显低(P<0.01)的项目为CREAT,较明显低 (P<0.05) 的为TRIG.结论本文建立了人工饲养条件下健康恒河猴血液学和血液生化值的正常指标,并讨论了年龄、性别对其正常指标的影响,可供参考.     

非酒精性脂肪性肝炎大鼠肝脏血管内皮生长因子表达的意义

目的探讨血管内皮生长因子（VEGF）在非酒精性脂肪性肝炎（NASH）大鼠肝脏的表达及意义。方法 20只大鼠随机分为对照组（10只）和模型组（10只）,分别给予标准饮食和高脂饮食16周,进行肝脏病理学检查和血生化指标分析;采用超高频小动物超声诊断仪检测肝脏及其血流动力学改变,利用分子生物学方法检测肝组织VEGF表达水平。结果模型组大鼠ALT、AST和TC增高（P〈0.05）。肝组织病理表现为大小泡混合性脂肪变性,伴肝细胞气球样变性、炎性细胞浸润、碎片状坏死和少量纤维组织增生。超声结果为肝脏增大,肝缘圆钝,实质回声细密增强,后方组织明显衰减,与脂肪肝病理结果一致;门静脉内径增大,肝静脉内径减小（p〈0.05）,静脉流速降低。肝组织VEGF蛋白和mRNA表达明显增加（P〈0.05）,VEGF蛋白主要表达在肝细胞和窦内皮细胞。结论 NASH肝脏VEGF蛋白和mRNA表达明显增加,VEGF可能参与NASH肝脏血流动力学的异常。     

青少年食蟹猴糖尿病模型的肝脏病理生理学研究

目的通过对胰岛素用量不足条件下链脲佐菌素诱导的青少年食蟹猴1型糖尿病模型肝脏病理生理学的研究,探讨长期高血糖所致青少年食蟹猴肝损伤特点及机制。方法通过静脉注射68 mg/kg的链脲佐菌素,诱导4只3岁的食蟹猴成为1型糖尿病模型,然后经长期的血糖监测和静脉糖耐量实验来评价该模型的可靠性及稳定性,造模4年后,对模型猴进行血生化、PAS染色、苏丹III染色及普通病理和超微病理等指标的检测,另外选取4只健康与模型猴年龄匹配的猴作为正常对照组,同时进行相应的检测。结果与正常对照组比较,糖尿病猴血清学检测指标中总胆汁酸、尿素氮、谷丙转氨酶、谷草转氨酶、胆碱酯酶、乳酸脱氢酶、总胆固醇、甘油三酯和低密度脂蛋白胆固醇明显升高。组织化学染色结果显示,与正常猴比较,糖尿病猴中央静脉区肝实质细胞肿胀,肝细胞PAS染色（糖原染色）加深,苏丹Ⅲ染色（脂肪染色）阳性细胞增多;电镜结果显示糖尿病猴肝细胞内胞质糖原颗粒增多;线粒体电子密度显著增高,结构不清;窦周隙内含有大量脂滴的肝星状细胞明显增多。结论在长期胰岛素用量不足血糖控制不理想的条件下,青少年食蟹猴1型糖尿病模型肝脏特异性的病理改变是肝糖原贮积和含有大量脂滴的肝星状细胞增生,这些病理改变与非酒精性脂肪肝病的病变特点存在显著不同,但其机制目前尚不清楚。     

实验性Ⅰ型糖尿病恒河猴的组织病理学观察

目的　观察实验性Ⅰ型糖尿病恒河猴的组织病理学变化。方法　 7只恒河猴分别静脉注射不同剂量的链脲佐菌素 (streptozotocin ,STZ) ,建立STZ性Ⅰ型糖尿病恒河猴模型 ,观察其心脏、肾脏、胰脏、脾脏等组织病理学变化。结果　动物胰岛数量明显减少 ,分布稀疏 ,残存胰岛萎缩 ,胰岛大小不等 ,成纤维细胞增生。肾小球增大 ,毛细血管壁增厚、僵硬 ,肾小管内膜细胞玻璃样变性 ,肾小球球囊内皮细胞增生。心肌变性、坏死、淤血 ,心肌细胞肥大 ,中、小血管壁增厚 ,血管壁纤维组织增加 ,冠状动脉内膜局部增厚 ,内皮细胞增生。脾脏小动脉硬化。结论　通过对STZ诱发的Ⅰ型糖尿病模型胰岛、肾脏和心脏等结构病理观察说明 ,该动物模型可用于糖尿病组织病理研究和药物疗效的评价。     

基于高通量测序的不同年龄恒河猴肠道菌群结构差异分析

目的观察不同年龄恒河猴肠道菌群结构和丰度的变化。方法 50只恒河猴,分为成年(5～10岁)、老年(10岁以上)2组,其中成年组33只,老年组17只。采集动物的新鲜直肠粪便,提取DNA后使用Illumina高通量测序平台对样本中细菌16S rDNA-V3区进行测序,定量分析肠道菌群的结构和丰度。结果老年组和成年组获得的优化序列数差异无显著性(P> 0.05)。α-多样性分析,老年组恒河猴肠道菌群的Chao1指数(P=0.0174)、Simpson指数(P=0.0258)、ACE指数(P=0.0121)与成年组比较降低,Shannon指数与成年组比较升高(P=0.0132)。老年组与成年组相比,在门水平,拟杆菌门(Bacteroidetes)相对丰度升高(P=0.0013),厚壁菌门(Firmicutes)、螺旋体门(Spirochaetes)、疣微菌门(Verrucomicrobia)、粘胶球形菌门(Lentisphaerae)相对丰度降低(P=0.0283,P=0.0002,P=0.0482,P=0.0242)。在科水平,Prevotellaceae相对丰度升高(P=0.0001),Ruminococcaceae、Clostridiales、Spirochaetaceae、Christensenellaceae相对丰度降低(P=0.0039,P=0.0080,P=0.0002,P=0.0021)。在属水平,老年组unidentified_Prevotellaceae相对丰度升高(P=0.0001),乳杆菌属(Lactobacillus)、八迭球菌(Sarcina)、unidentified_Spirochaetaceae相对丰度降低(P=0.0114,P=0.0227,P=0.0028)。β-多样性分析,老年组肠道菌群与成年组分布在不同区域,差异有显著性(P=0.003)。LEfSe分析,在成年组,链球菌属(Streptococcus)、布赫纳氏菌属(buchnera)、乳杆菌属(lactobacillus)是具有统计学意义的生物标记物。结论恒河猴肠道菌群的结构随年龄增长而改变。丰度降低,多样性增高。     

Glypican-3在肝脏良恶性病变中的表达及临床意义

目的:研究Glypican-3在肝脏良、恶性病变中的表达,探讨其临床诊断意义.方法:采用免疫组织化学S-P法检测Glypiean-3在肝细胞性肝癌、肝局灶结节性增生、肝细胞腺瘤及正常肝组织中的表达.结果:Glypican-3在肝细胞性肝癌中的阳性率为81.25%,而在肝脏良性病变肝局灶结节性增生、肝细胞腺瘤及正常肝组织中均为阴性.结论:Glypican-3有助于肝脏良、恶性病变的鉴别诊断.     

人工饲养恒河猴、食蟹猴的繁殖性能初报

目的探索北京地区人工饲养恒河猴与食蟹猴的繁殖性能,为温带地区猕猴的人工饲养和繁殖方式提供借鉴。方法对军事医学科学院实验动物中心饲养的317只恒河猴繁殖群（30只雄猴,287只雌猴）和78只食蟹猴繁殖群（8只雄猴,70只雌猴）近两年的繁殖性状进行观察和统计分析。结果恒河猴母猴妊娠率、繁殖率和成活率分别为60.73%、54.45%和96.89%。食蟹猴母猴妊娠率、繁殖率和成活率分别为79.86%、56.12%和75.00%。结论食蟹猴和恒河猴可以成功的在温带地区饲养和繁殖,但人工饲养食蟹猴的妊娠率与产仔率较恒河猴高,而仔猴成活率则低于恒河猴。     

表现神经症状的SIVmac251感染猴大脑基底节病毒gp120序列变异分析

目的 研究猴免疫缺陷病毒SIVmac251在中国恒河猴感染传代过程中产生的可能的神经侵袭性和神经嗜性及其分子机制.方法 从静脉感染SIVmac251-155p6N的8只实验猴中出现严重神经症状的1只猴中,监测病毒及免疫指标变化,观察临床症状、猴脑组织病变,单拷贝PCR扩增病毒gp120序列并分析变异及糖基化位点变化情况.结果 感染猴晚期出现明显艾滋病脑病症状,病理切片显示脑组织出现多核巨细胞及神经元变性、坏死.脑基底节分离出单一序列病毒,其氨基酸序列与血浆病毒及感染毒株SlVmac251-155p6序列差异主要位于Gp120的V1和V4区,并且在C1区66位出现一个糖基化位点缺失.结论 SIVmac251在猴体长期传代过程中表现出神经嗜性毒株的特征,对AIDS脑病研究具有重要意义.     

恒河猴麻疹病的诊断与治疗

目的探索恒河猴麻疹病的诊断、治疗及防制方法。方法隔离病猴,采集猴血清,环境消毒,对病死猴进行病理学观察、抗体ELISA和病毒免疫组织化学检测,以及治疗。结果病猴被确诊为患猴麻疹,隔离发病猴3只,其中死亡1只,康复2只,未出现麻疹病的进一步扩大流行。采用头孢曲松钠、地塞米松、利巴韦林等治疗取得了显著治疗效果。结论预防是控制麻疹病的关键,运输及环境改变是致病的诱因,快速诊断、科学用药和综合防治是减少损失的关键。     

Studies on Hepatocystis sp. in rhesus monkeys from Yunnan, China

A survey for the prevalence of Hepatocystis sp. was done on 10 rhesus monkeys (M. mulatta) from Yunnan, China. Examinations were performed on blood smears to detect erythrocytic gametocytes of the parasite, and on livers to detect merocysts. In 6 out of 10 monkeys, Hepatocystis sp. infection was confirmed. The gametocytes took about 6 days to reach maturity. The fully grown macrogametocytes were about 8 microns in diameter. The cytoplasm was stained pale lilac and the nucleus consisted of dense chromatin dots lying in an unstained zone. The microgametocytes had cytoplasm dyed a biscuit color and large nuclei dyed pink. In the pathological section of livers, the merocyst measured about 3 mm in diameter and had a smooth outline without any projecting limb. The characteristics of this protozoan species were very similar to those of H. taiwanensis. However, more work should be done to clarify the relationship between this species and H. taiwanensis.     

Age-Related Changes of Elements in the Coronary Arteries of Monkeys in Comparison with Those of Humans

To elucidate compositional changes of the coronary artery with aging, the authors investigated age-related changes of elements in the coronary arteries of rhesus and Japanese monkeys by direct chemical analysis in comparison with the coronary arteries of Japanese and Thai. Used monkeys consisted of 38 rhesus monkeys and 23 Japanese monkeys, ranging in age from newborn to 33 years. After perfusion with a fixative, the hearts were resected from the monkeys, and the anterior interventricular branches of the left coronary artery and the right coronary arteries were resected from the hearts. After ashing of the arteries, element contents were determined by inductively coupled plasma-atomic emission spectrometry. It was found that the Ca and P contents did not increase in both the left and right coronary arteries of rhesus and Japanese monkeys at old age. The average contents of Ca and P decreased by 13% and 25% in the left coronary arteries more than 20 years of age in comparison with those below 20 years of age, whereas they decreased by 4% and 15% in the right coronary arteries more than 20 years of age in comparison with those below 20 years of age. This finding indicated that atherosclerosis scarcely occurred in both the left and right coronary arteries of rhesus and Japanese monkeys at old age. In contrast with monkeys, atherosclerosis occurred frequently in the coronary arteries of Japanese and Thai at old age.     

Species preference by infant macaques with controlled social experience

In Experiment 1, infant Japanese monkeys and rhesus monkeys were artificially reared in pairs with conspecific or heterospecific monkeys. Preferences of these monkeys for a variety of pictures of Japanese monkeys and rhesus monkeys were repeatedly tested during the first 1 or 2 years of life. The duration of lever-pressing responses to see those pictures was a measure of the preference. All monkeys, Japanese or rhesus, preferred pictures of rhesus monkeys to pictures of Japanese monkeys, without regard to their social experiences. Experiment 2, with an adult Japanese monkey as the subject, and Experiment 3, with different pictures as stimuli, suggested that this preference was not a consequence of any bias in the pictures used. In Experiment 4, a Japanese monkey reared by a rhesus foster mother and rhesus monkeys reared by Japanese monkey mothers received the same preference test. The Japanese monkey infant preferred to see pictures of rhesus monkeys. However, rhesus infants did not show clear species preferences. These results suggest that infants of both Japanese and rhesus monkeys have a native tendency to prefer to see physical characteristics of rhesus monkeys over Japanese monkeys.     

Serum dehydroepiandrosterone sulfate concentrations across the life span of laboratory-housed rhesus monkeys

Cross-sectional studies of humans have shown that dehydroepiandrosterone sulfate (DHEAS) peaks shortly after sexual maturation and declines thereafter, suggesting that the progressive reduction in DHEAS may play a role in the aging process and in the development of age-related morbidity. The present study examines changes in DHEAS concentrations across the life span of rhesus monkeys as part of the development of this primate model for studies of aging. Serum concentrations of DHEAS were measured in 792 laboratory-housed rhesus monkeys (Macaca mulatta) aged 0.5-36 years (527 females, 265 males). DHEAS concentrations in all monkeys were used to formulate an equation that describes two levels of decline of DHEAS with age. The most rapid decline occurs from infancy until approximately 5 years of age. The decline then occurs gradually with increasing age. There were no signs of an andrenarche just prior to sexual maturation, as is seen in humans or the great apes. This equation can be used to predict the expected mean serum DHEAS concentration and normal ranges of male or female rhesus monkeys at any age greater than 5 months.     

Characterization of dermatologic changes in geriatric rhesus macaques

Abstract: Nonhuman primates are frequently used for aging studies. We observed a high prevalence of skin disease among a group of geriatric rhesus monkeys (mean age ? 25 years; n ? 9) used in aging behavioral studies. Gross and histopathologic changes in the skin of these geriatric rhesus were compared with skin from control adult monkeys (mean age ? 10; n ? 4) and sun-exposed monkeys (mean age ? 11; n = 4) to characterize age-related skin changes. Biopsy specimens were taken from four specified skin locations (lateral to bridge of nose, ventral midline, dorsal midline, perineal area) and from additional areas where skin lesions were present. Samples were routinely processed and evaluated by light microscopy. Blood samples were collected and tested for estrogen, thyroid-stimulating hormone, triiodothyronine, thyroxine, and Cortisol levels. The axilla was swabbed and samples were obtained for bacterial culturing. All nine of the geriatric monkeys had notable dermal lesions, while one of the control monkeys and one of the sun-exposed monkeys had abnormal findings. Major gross findings included increased areas of erythematous skin, wrinkling, focal skin scaling, thinning of hair, foot calluses, and exudative lesions. Histologic skin changes included subacute dermatitis, acanthotic dermatitis, and a lesion resembling an early solar lentigo in the sun-exposed animal. These changes were not associated with hormonal abnormalities or bacterial pathogens. Histologic changes are compatible with nonspecific skin changes observed in elderly humans. This study establishes a baseline of dermatologic changes of the aging rhesus macaque.     

Evaluation of cynomolgus (Macaca fascicularis) and rhesus (Macaca mulatta) monkeys as experimental models of acute Q fever after aerosol exposure to phase-I Coxiella burnetii

BACKGROUND AND PURPOSE: Q fever is a disease of humans. Vaccines to prevent this disease have demonstrated efficacy in rodents and must also be evaluated for efficacy in a nonhuman primate model. Preliminary to vaccine efficacy experiments, cynomolgus and rhesus monkeys were evaluated as suitable experimental models of acute Q fever. METHODS: Both species of monkeys were challenged with aerosolized 10(5) virulent phase-I Coxiella burnetii Henzerling strain, and clinical and serologic responses were determined. RESULTS: Radiographic changes were observed in seven of eight monkeys of both species; however, changes in cynomolgus monkeys tended to be more significant. Between 7 and 10 days after challenge, all rhesus monkeys and 88% of cynomolgus monkeys were bacteremic. Sequential increases in antibody responses to C. burnetii phase-I and phase-II whole cells and phase-I lipopolysaccharide were observed in both species. Although the maximal rectal temperature increase was similar in both species, duration of fever was slightly longer in rhesus monkeys. Clinical features were similar to those described in human acute Q fever patients. CONCLUSIONS: On the basis of the more pronounced radiographic changes in cynomolgus monkeys, we favor use of this species for future studies of vaccine efficacy.     

Stable chromosome rearrangements in the somatic cells of monkeys subjected to acute radiation exposure

Frequencies of stable chromosome rearrangements in bone marrow cells of rhesus monkeys (Macaca mulatta) have been determined for following time periods: from 0.25 to 6.0 and from 10.0 to 18.0 years after gamma-irradiation at doses of 154.8-167.7 mC/kg. The time of the occurrence of pathological clones and the character of their formation in those cells, whose markers were presented by chromosome rearrangements of the same type, have been defined. Some animals showed the tendency towards the increase in the frequency of uni-type rearrangements in the pathological cell clones. This phenomenon could be a potential precursor of the pathological processes in irradiated individuals.