Development and characterization of a guinea pig model for Marburg virus

The Angolan strain of Marburg virus （MARV/Ang） can cause lethal disease in humans with a case fatality rate of up to 90%, but infection of immunocompetent rodents do not result in any observable symptoms. Our previous work includes the development and characterization of a MARV/Ang variant that can cause lethal disease in mice （MARV/Ang-MA）, with the aim of using this tool to screen for promising prophylactic and therapeutic candidates. An intermediate animal model is needed to confirm any findings from mice studies before testing in the gold-standard non-human primate （NHP） model. In this study, we serially passaged the clinical isolate of MARV/Ang in the livers and spleens of guinea pigs until a variant emerged that causes 100% lethality in guinea pigs （MARV/Ang- GA）. Animals infected with MARV/Ang-GA showed signs of filovirus infection including lymphocytopenia, thrombocytopenia, and high viremia leading to spread to major organs, including the liver, spleen, lungs, and kidneys. The MARV/Ang-GA guinea pigs died between 7-9 days after infection, and the LD50 was calculated to be 1.1x10-1 TCID50 （median tissue culture infective dose）. Mutations in MARV/Ang-GA were identified and compared to sequences of known rodent-adapted MARV/Ang variants, which may benefit future studies characterizing important host adaptation sites in the MARV/Ang viral genome.

Guinea pig model of tuberculosis

Animal models are being developed for testing different vaccine candidates as well as testing of new antitubercular since a long time.Mice,guinea pigs and rabbits are animals which are frequently used.Though each model has got its merits as well as demerits and each of them differ from human tuberculosis in one aspect or the other but none of the model completely mimics the human disease.Out of the different animal species, guinea pig model is one of the better models as it is very sensitive to M.tuberculosis infection but it has certain limitations like paucity of immunological reagents.However,it is the best model for tuberculosis research.

Dynamic changes of ocular biometric parameters:a modified form-deprivation myopia model of young guinea pigs

AIM: To evaluate the dynamic ocular biometric changes of a modified form-deprivation myopia model in young guinea pigs. METHODS: The animals were randomly assigned to two groups: the monocularly deprived facemask group (MDF, with all the right eyes covered, n=24) and the normal control group(free of facemask, n=24). Each group was then equally divided into four subgroups which were followed up for 2, 4, 6 and 8 weeks, respectively. Parameters measured from every eye included refraction, corneal curvature, axial length and the dry weight of sclera at the posterior pole. RESULTS: All the facemasks remained in place during the follow-up. The covered eyes developed myopia with the vitreous chamber lengthening and the dry weight of posterior sclera reduced at each time point compared with the contralateral uncovered (P<0.05 at all time points). The changes had a linear correlation with the deprivation time (P<0.05). There were no significant differences in all the parameters between the uncovered eyes of MDF group and the normal control group (P>0.05 at all time points). CONCLUSION: Monocular form deprivation with the facemask is highly effective and non-invasive in inducing axial myopia in guinea pigs. The axial myopia is mainly caused by the increased vitreous chamber length and the weakened posterior sclera rigidity. The form-deprivation eye didn't interfere with the natural development of the contralateral eye.

An end-to-end anastomosis model of guinea pig bile duct:A 6-mo observation

AIM:To establish the end-to-end anastomosis (EEA) model of guinea pig bile duct and evaluate the healing process of bile duct.METHODS:Thirty-two male guinea pigs were randomly divided into control group,2-,3-,and 6-mo groups after establishment of EEA model.Histological,immunohistochemical and serologic tests as well as measurement of bile contents were performed.The bile duct diameter and the diameter ratio (DR) were measured to assess the formation of relative stricture.RESULTS:Acute and chronic inflammatory reactions occurred throughout the healing process of bile duct.Serology test and bile content measurement showed no formation of persistent stricture in 6-mo group.The DR revealed a transient formation of relative stricture in 2-mo group in comparation to control group (2.94 ± 0.17 vs 1.89 ± 0.27,P=0.004).However,this relative stricture was released in 6-mo group (2.14 ± 0.18,P=0.440).CONCLUSION:A simple and reliable EEA model of guinea pig bile duct can be established with a good reproducibility and a satisfactory survival rate.

Guinea pigs as an animal model for sciatic nerve injury

The overwhelming use of rat models in nerve regeneration studies is likely to induce skewness in treatment outcomes.To address the problem,this study was conducted in 8 adult guinea pigs of either sex to investigate the suitability of guinea pig as an alternative model for nerve regeneration studies.A crush injury was inflicted to the sciatic nerve of the left limb,which led to significant decrease in the pain perception and neurorecovery up to the 4th weak.Lengthening of foot print and shortening of toe spread were observed in the paw after nerve injury.A 3.49 ± 0.35 fold increase in expression of neuropilin 1（NRP1） gene and 2.09 ± 0.51 fold increase in neuropilin 2（NRP2） gene were recorded 1 week after nerve injury as compared to the normal nerve.Ratios of gastrocnemius muscle weight and volume of the experimental limb to control limb showed more than 50% decrease on the 30 th day.Histopathologically,vacuolated appearance of the nerve was observed with presence of degenerated myelin debris in digestion chambers.Gastrocnemius muscle also showed degenerative changes.Scanning electron microscopy revealed loose and rough arrangement of connective tissue fibrils and presence of large spherical globules in crushed sciatic nerve.The findings suggest that guinea pigs could be used as an alternative animal model for nerve regeneration studies and might be preferred over rats due to their cooperative nature while recording different parameters.

Electrophysiological changes of autonomic cells in left ventricular outflow tract in guinea pigs with iron deficiency anemia complicated with chronic heart failure

Objective: To investigate the electrophysiological changes of autonomic cells in left ventricular outflow tract in guinea pigs with iron deficiency anemia complicated with chronic heart failure.Methods: Guinea pigs model of iron deficiency anemia complicated with chronic heart failure in 10 guinea pigs of the experimental group was made by feeding a low iron diet,pure water and subcutaneous injection of isoproterenol. The control group consisting of 11 guinea pigs was given normal food, normal water and injected with normal saline. The left ventricular outflow tract model specimen was also prepared. The standard microelectrode technique was used to observe electrophysiological changes of autonomic cells in the outflow tract of left ventricular heart failure complicated with iron deficiency anemia in guinea pig model. The indicators of observation were maximal diastolic potential, action potential amplitude, 0 phase maximal depolarization velocity, 4 phase automatic depolarization velocity, repolarization 50% and 90%, and spontaneous discharge frequency.Results: Compared with the control group, 4 phase automatic depolarization velocity,spontaneous discharge frequency and 0 phase maximal depolarization velocity decreased significantly(P < 0.01) and action potential amplitude reduced(P < 0.01) in model group. Moreover, repolarization 50% and 90% increased(P < 0.01).Conclusions: There are electrophysiological abnormalities of the left ventricular outflow tract in guinea pigs with iron deficiency anemia complicated with heart failure.

Myopia induced by flickering light in guinea pigs: a detailed assessment on susceptibility of different frequencies

AIM: To investigate the effectiveness and feasibility of inducing myopia in guinea pigs by flickering light (FL) stimulation with different frequencies. METHODS: Seventy 2 -week-old guinea pigs were randomly assigned to six groups: five FL groups and a control group (n =12 for each). Animals in the five FL groups were raised under 500lx illumination with a duty diurnal cycle of 50% at a flash rate of 5, 1, 0.5, 0.25 and 0.1Hz respectively. Those in the control group were reared under steady 250lx illumination. Refraction, axial length, and radius of curvature were measured before and at 2, 4, 6, 8, 10 and 12 weeks after treatment. At week 12, the eyeballs were taken out and three ocular dimensions and dry weight of sclera were measured. RESULTS: A myopic shift and axial eye length increase developed in the five FL groups. Stimulation at 0.5Hz caused greater changes in myopic shift, axial elongation, eyeball dimension, and dry weight of sclera than stimulation at other frequencies. Compared with controls, eyes in 0.5Hz group were approximately -5.5 ±1.5D more myopic with increase in horizontal, vertical, axial dimensions by 0.89 ±0.3mm, 0.69 ±0.2mm, 1.12 ±0.2mm respectively and with increase in dry weight of sclera by 0.44mg. CONCLUSION: Chronic exposure to periodic illumination at temporal frequency is attended by development of excessive ocular enlargement and myopic refractive error. Emmetropization could bedisrupted differently by frequency alteration.

Effect of green flickering light on myopia development and expression of M1 muscarinic acetylcholine receptor in guinea pigs

AIM： To investigate the effects of green flickering light on refractive development and expression of muscarinic acetylcholine receptor（mAChR） M1 in the eyes of guinea pigs.METHODS： Thirty guinea pigs（15-20 days old） were randomly divided into three groups（n=10/group）. Animals in group I were raised in a completely closed carton with green flickering light illumination. Those in group II were kept in the open top closed carton under normal natural light. Guinea pigs were raised in a sight-widen cage under normal natural light in group III. The refractive status and axial length were measured before and after 8 weeks＇ illumination. Moreover, total RNA extracted from retinal, choroidal, and scleral tissues were determined by real-time reverse transcription polymerase chain reaction（RT-PCR）. The expressions of the receptor M1 were also explored in the retina, choroid, and sclera using immunohistochemistry.RESULTS： There was a remarkable reduction in refractive error and increase in axial length after 8-weeks＇ green flickering light stimulation（P〈0.001）. The expression of M1 receptor mRNA in sclera and retina in myopia group were remarkably lower than that in group II and III（P〈0.01）. Significant reduced expression of M1 receptor stimulated by green flickering light in retina and sclera tissues were also observed（P〈0.05）. However, there was no M1 receptor expression in choroid in 3 groups.CONCLUSION： Myopia can be induced by 8 weeks＇ green flickering light exposure in the animal model. M1 receptor may be involved causally or protectively in myopia development.

变应性鼻炎相关动物模型研究进展

目的综述变应性鼻炎(allergic rhinitis,AR)相关动物模型的研究进展,为深入研究AR的发病机制及药物评价提供参考。方法通过对国内外文献的查阅,从AR模型动物的种类、特点、模型种类、建模方法、模型成功的标准和评价指标等方面进行总结。结果变应性鼻炎相关动物模型包括西医病理模型和中医病症结合模型,动物选择多使用豚鼠、小鼠、大鼠、新西兰兔等。结论总结已有AR动物模型的种类、方法和评价指标以及在AR发病机制研究中的应用,可为后续AR的深入研究提供参考。

Efficacy Assessment of Whitening Cosmetics in Animal Models

Animal skin is generally preferred to evaluate the efficacy and safety:several animal models have been used,e.g.,the guinea pig,the mouse,and the zebrafish.The epidermis of guinea pigs displays a moderate number of melanocytes and melanosomes distributed in a similar way to human skin.Guinea pig and human skins have given the close morphologic and functional similarities(similar epidermis thickness,similar epidermal cells turnover time,etc.).The zebrafish presents several advantages,including easy maintenance and handling of the animals,short generation times,and high efficiency of drug penetration through the skin.To establish the animal model and to assess whitening efficacy and safety for whitening products.

实验性近视豚鼠模型研究进展

近视发病率逐年上升,严重影响着公众生活质量,为探索近视的发病机制,迄今已经建立了多种实验性近视动物模型。豚鼠在近视研究方面具有明显的优点,目前是亚洲实验室最常见的近视动物模型,但是不同的造模方式各有优缺点,了解不同的造模方式有利于选择适合的动物模型以及匹配不同的研究目的,可使研究结果更具说服力。本文对近年来豚鼠近视模型的不同造模方式及其特点、以及豚鼠眼部组织形态学的变化等方面进行简要综述,为进一步研究近视发生发展的分子机制寻找新的治疗策略提供一定的参考。

基于多指标评价的胆囊炎豚鼠模型的建立与优化

目的探讨胆囊炎豚鼠模型的建立及优化方法,为进一步优化实验设计和研究胆囊炎的发病、治疗及作用机制提供实验基础。方法采取盐酸林可霉素皮下注射的方式,建立胆囊炎豚鼠模型,通过观察豚鼠一般状态、胆囊B超、血常规指标和肝胆组织病理学改变,确定胆囊炎模型的稳定性及应用前景。结果一般状态观察发现,模型组豚鼠出现不同程度的饮食减少、体质量下降、活动减少、毛发疏松无光泽、精神萎靡或烦躁不安等。胆囊B超结果显示,与对照组豚鼠比较,造模剂量越高,豚鼠的胆囊壁增厚越明显(P<0.05);血常规指标检测发现,造模剂量越高,血液炎性指标白细胞计数(white blood cell count,WBC)、淋巴细胞计数(lymphocyte,LYM)、中性粒细胞计数(neutrophil,NEUT)、单核细胞计数(monocyte,MONO)上升越显著(P<0.05);苏木精-伊红染色结果显示,造模剂量越高,胆囊和肝脏组织结构病变、炎性细胞浸润、肝细胞变性坏死等病理变化更加明显。结论本研究通过影像学指标结合血液及病理指标,多因素综合评价胆囊炎造模效果以及炎症模型的稳定性,较常规的胆囊病理分析法或结合血清炎性细胞因子酶联免疫吸附试验检测法更为直观、精确且廉价,且为药物治疗效果评价提供科学有效的检测指标;同时,确定豚鼠胆囊炎造模剂量为盐酸林可霉素120mg/kg的模型最为稳定,且不易自愈。

应用Python编程数字化测量豚鼠角膜曲率及离心率

目的探索一种编程数字化技术和数学几何原理相结合对豚鼠眼球形态学参数进行量化分析的方法。方法选取22只3周龄清洁级雄性三色豚鼠,采用过量麻醉法处死并取出眼球,采用1300万像素微距仪的高拍模式进行水平面及矢状面拍照,图片导入pycharm编程软件。应用Python 3.9预先编写好的分析程序,先通过刻度尺获取图片像素与实际距离的换算系数,再对角膜表面进行圆弧拟合及圆锥曲线拟合。圆弧拟合后的结果经换算后计算出豚鼠的角膜曲率半径;通过圆锥曲线通用方程拟合(Ax^(2)+Bxy+Cy^(2)+Dx+Ey+F=0),得出角膜表面的离心率e值;通过对全角膜及中央区3 mm的拟合,评估角膜的非球面性质。结果应用Python编程数字化方法可以完整清晰地展现豚鼠的角膜轮廓。横切面上,数字化拟合中央3 mm、数字化拟合全角膜以及曲率计测量全角膜曲率比较,差异无统计学意义(F=1.693,P=0.190);矢状面上,3种方法测得的角膜曲率比较,差异有统计学意义(F=3.500,P=0.030),其中曲率计测量全角膜的角膜曲率明显大于数字化拟合全角膜,差异有统计学意义(P<0.05)。横切面和矢状面上,3种方法测得的角膜曲率半径比较,差异均无统计学意义(F=1.817,P=0.170;F=2.050,P=0.133)。离心率测量结果显示,横切面和矢状面数字化拟合中央区3 mm处e值分别为0.55±0.15和0.53±0.17,分别低于数字化拟合全角膜e值的0.66±0.10和0.64±0.14,差异均有统计学意义(t=-4.860、-5.210,均P<0.01)。结论应用Python编程数字化方法测量豚鼠角膜曲率及离心率切实可行。

豚鼠与人眼球结构及生物学参数的比较研究进展

豚鼠是目前国内最为广泛使用的研究视觉系统的动物模型之一,尽管其眼球的解剖和形态特征以及生理功能方面都与人类接近,但两者间的差异性也是我们不可忽视的。充分了解豚鼠和人眼之间存在的解剖、生理和病理学差异,能够为眼科研究者合理、有效地选择及建立相关疾病动物模型提供科学的理论依据。因此,本文就眼球的主要结构及其生物学参数对人与豚鼠的眼球进行比较分析,为以豚鼠为动物模型的视觉系统科学研究提供一定的参考价值。

盐酸灌注豚鼠食管反流性疾病模型的建立

目的:利用反复酸灌注的方法模拟人胃食管反流,建立豚鼠食管炎模型,以便为探讨反流相关性呼吸系统疾病提供实验动物模型。方法:将胃管插入豚鼠食管至食管中、下端,灌注含0.5%胃蛋白酶的0.1mol/LHCl(8drops/min,20min/d),连续灌注14d。结果:酸灌注后出现明显食管炎症病理改变,光镜下可见食管下段粘膜基底细胞层增生,乳头延长、角化过度。部分食管鳞状上皮过度增生、核增大、变圆。固有层慢性炎症细胞浸润明显,粘膜下层内血管扩张、充血。气管、支气管粘膜也见水肿、基底膜增厚,部分上皮脱落,粘膜和粘膜下层炎症细胞浸润。结论:连续酸灌注的方法成功地复制了豚鼠反流性食管炎模型,同时伴有气管、支气管粘膜炎症,为探讨反流相关性呼吸系统疾病的发病机制提供了帮助。

构建糖尿病膀胱病豚鼠模型及其尿动力学评价

背景:糖尿病性膀胱病是糖尿病患者最常见的慢性并发症之一,建立糖尿病膀胱病动物模型为相关研究提供实验动物平台。目的:建立糖尿病膀胱病豚鼠模型并进行尿动力学评价。方法:50只英国种短毛雌性豚鼠,实验组(n=42)以单次腹腔注射链脲佐菌素法诱导糖尿病豚鼠,对照组(n=8)注射相应剂量空白枸橼酸缓冲液,分别在9周和12周时行尿动力学检查,确定膀胱功能失代偿豚鼠即糖尿病性膀胱病组和代偿豚鼠即代偿组豚鼠尿动力学特点。结果与结论:42只豚鼠有20只成功诱导出糖尿病。糖尿病豚鼠中,9周时9只糖尿病组豚鼠,6只膀胱功能代偿,3只失代偿;12周时,另外9只糖尿病组豚鼠,1只膀胱功能代偿,8只失代偿(89%)。糖尿病性膀胱病组豚鼠残余尿量增加(0.72±0.08)mL、最大逼尿肌压下降(0.63±0.05)kPa、膀胱容量增加(2.01±0.05)mL及膀胱顺应性增加(3.47±0.41)mL/kPa,与对照组及代偿组比较,差异均存在显著性意义(P<0.001)。豚鼠一般可在诱导糖尿病成功后12周发生糖尿病性膀胱病,表现出膀胱残余尿量增加等相应的尿动力学改变。

猪链球菌2型引致脑炎及败血症的豚鼠模型

选用不同日龄的健康豚鼠 132只 ,分组经不同途径接种对猪具有致病性的猪链球菌 2型江苏分离株 HA980 1,引致脑炎及败血症 ,建立了动物模型。试验表明 ,小于 2 4日龄提前断奶的豚鼠对该菌株较易感 ,最佳感染途径是皮下注射 ,腹腔、鼻腔次之。感染豚鼠表现出典型脑炎的临床症状及病理变化。经重复试验测得该菌株对豚鼠的 L D50 为 5 .5× 10 6cfu,从感染死亡豚鼠脑脊液、大脑、血液及各实质器官均可分离出该病原菌 ,与仔猪自然感染情况相似。该动物模型的建立为进一步探究猪链球菌 2型感染的体内动态分布、感染机制。

壁虎粉对哮喘豚鼠模型干预作用的实验研究

目的探讨壁虎粉平喘的部分作用机理。方法采用卵蛋白致敏激发豚鼠哮喘为模型,观察壁虎粉干预组、氨茶碱对照组和哮喘模型组动物哮喘发病情况,肺泡灌洗液(BALF)中EOS含量及豚鼠肺组织病理学的改变。结果壁虎粉和氨茶碱组BALF中EOS含量明显低于哮喘模型组,病理学提示壁虎粉能抑制局部炎症细胞浸润、保护气管粘膜的完整性。结论壁虎粉可通过抑制气道炎症,促进EOS凋亡等途径发挥平喘作用。

艾蒿花粉诱导豚鼠过敏反应

目的:研究艾蒿花粉粗提物(MPE)和其主要成分之一artemisia vulgaris 1(Art V1)能否诱导豚鼠过敏反应,为艾蒿花粉过敏症研究建立动物模型。方法:艾蒿花粉粗提物或Art V1混悬于佐剂氢氧化铝凝胶中,每间隔10 d致敏豚鼠1次,共4次,然后以艾蒿花粉粗提物或Art V1抗原滴鼻诱发鼻炎症状。气道高反应性(AHR)、炎症细胞和肺组织病理的观察于Art V1气雾攻击5 d后,以乙酰甲胆碱(Mch)气雾吸入激发AHR,测定气道阻力和动态肺顺应性,计数和分类计数支气管肺泡灌洗液(BALF)中的炎症细胞,观察肺组织病理学改变。结果:Art V1组豚鼠在抗原激发下喷嚏次数和抓鼻次数显著增加,吸入Mch后气道阻力明显增加,动态肺顺应性明显降低,Mch气雾吸入可激发AHR;MPE组豚鼠喷嚏次数有所增加,气道反应性有所升高;两组BALF和病理切片均显示明显的嗜酸性粒细胞和中性粒细胞浸润。结论:艾蒿花粉粗提物和其主要成分Art V1均能诱导豚鼠过敏反应,Art V1致敏效果明显优于艾蒿粗提物。该模型的建立有利于过敏性疾病机制和治疗新药的研究。

咳嗽变异性哮喘豚鼠模型的构建

目的尝试制备一种咳嗽变异性哮喘(CVA)的豚鼠模型。方法30只雄性豚鼠饲养1周后,随机分为健康正常组和模型组,每组15只。模型组第1天肌注4%OVA溶液0.5ml,同时腹腔注射2%Al(OH)30.2ml,14d后,模型组用1%OVA溶液雾化后攻击,隔天1次,每次15s,共7次。第29天,两组豚鼠用10-4mol/L辣椒素溶液引咳。结果通过对咳嗽次数、肺病理切片、肺泡灌洗液、外周血等指标的观测,发现模型组的咳嗽次数多于健康正常组;与健康正常组比较,模型组的病理损伤明显;从肺泡灌洗液和血内嗜酸性粒细胞计数及白细胞计数上看,模型组与健康正常组两组存在统计学差异,前者较后者计数均有升高。结论这种改进后方法能成功地建立咳嗽变异性哮喘模型。