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International Journal of Ophthalmology(English edition) 2023年第9期16卷 1450-1455页

作者： Wei Fang Jing Zhai Zhen-Bin Qian Hai-Dong Li Meng-Di Wang Li-Jun Shen The Eye Hospital of Wenzhou Medical University School of Opthalmology&OptometryWMUZhejiang Eye HospitalHangzhou 310000Zhejiang ProvinceChina

AIM:To evaluate whether a novel tyrosine kinase inhibitor nintedanib could inhibit basic fibroblast growth factor(bFGF)and vascular endothelial growth factor(VEGF)simultaneously for retinal vascular disease in vivo.METHODS:After a laser induced rabbit retinal vein occlusion(RVO)model was made,0.5 mg of nintedanib was injected intravitreally in the left eye on the third day while the right eye was as a control.Intracameral samples were taken on the day before laser treatment and days 1,3,7,14,21,and 28 after treatment.Enzyme-linked immunosorbent assay(ELISA)was used to test the bFGF and VEGF-A concentrations in the aqueous humor.RESULTS:Both bFGF and VEGF-A rose significantly on the third day after laser treatment in both eyes.In the control eye the bFGF concentration peaked on the 14th day while the VEGF-A concentration dropped rapidly soon after the third day.After nintadanib injection in the study eye,both bFGF and VEGF-A showed a significant reduction on the 4th day(7th day after laser treatment)when compared to the control eye,and kept on low level in the following several weeks.CONCLUSION:Intravitreal injection of nintedanib can inhibit the expression of bFGF and VEGF in the process of RVO model to a certain extent,which is expected to become a new method for the treatment of retinal vascular diseases or fibrotic diseases.

关键词： retinal vein occlusion nintedanib tyrosine kinase inhibitor basic fibroblast growth factor vascular endothelial growth factor rabbit model

Accelerated and enhanced osteointegration of MAO-treated implants:histological and histomorphometric evaluation in a rabbit model

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International Journal of Oral Science 2018年第2期10卷 81-91页

作者： Xin Li Haiyang Xu Baodong Zhao Shuai Jiang Department of Oral Implantology the Affiliated Hospital of Qingdao UniversityQingdaoChina School of Stomatology Qingdao UniversityQingdaoChina Department of Oral Implantology of Zibo Central Hospital ZiboChina

Microarc oxidation（MAO） has become a promising technique for the surface modification of implants. Therefore, the aims of this study were to further quantitatively and qualitatively evaluate the osteointegration abilities of MAO-treated and smooth surface（SF） implants in vivo and to investigate the areas in which the superiority of MAO-treated implants are displayed. In a rabbit model,a comprehensive histomorphological, osteogenic, mineralizational, and integrative assessment was performed using light microscopy, fluorescence microscopy, confocal laser scanning microscopy, and radiographic analyses. Compared with the SF groups, the MAO-treated groups exhibited more active contact osteogenesis, as well as distant osteogenesis, under fluorescence examination, the mineral apposition rate was found to be greater for all of the MAO-treated implants, and the osteointegration index（OI） value was greater in the MAO-treated groups at different times. In conclusion, the calcium-rich amorphous layer created by MAO provided a better environment for osteointegration, with more active contact osteogenesis, a more rapid mineral apposition rate and greater OI values.

关键词： MAO Accelerated and enhanced osteointegration MAO-treated implants histological histomorphometric evaluation rabbit model

Development of fusiform aneurysms induced by topical application of elastase in a rabbit model

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Chinese Neurosurgical Journal 2017年第4期3卷 213-218页

作者： Guoquan Jiang Zifu Li Xiaochun Jiang Zhenbao Li Shanshui Xu Xinggen Fang Department of Neurosurgery Second Affiliated Hospital of Wannan Medical College Wuhu China Department of Neurosurgery Changhai HospitalSecond Military Medical University Shanghai China Department of Neurosurgery First Affiliated Hospital of Wannan Medical College Wuhu 241000 China

Research on the etiology and pathophysiology of fusiform aneurysm has been impeded due to the inability to collect fusiform aneurysm specimens. We aim to resolve this through the development of a novel fusiform aneurysm model in rabbits. Sixty New Zealand White rabbits were divided into ten groups (n = 6 per group): groups A, B, C, D, E and groups a, b, c, d, e. Elastase, at a concentration of 0, 0.5, 1, 2.5 and 5 U/μL respectively was administered to each rabbit to incubate their carotid arteries. Three weeks later, angiography, histomorphometry, immunohistochemistry and immunofluorescent were performed. Heparin administration is indispensable. No thrombosis was observed in groups A, B, C, D and E, whereas, increased thromboembolism occurred in groups a, b, c, d and e. Based on the size and wall thickness of aneurysms specimens, 5 U/μL was the optimal concentration of elastase to induce fusiform aneurysms. At 5 U/μL, the intraluminal carotid diameter increased significantly from 2.50 ± 0.32 mm to 3.11 ± 0.55 mm (p modeled in rabbit carotid artery adventitia incubation by porcine pancreatic elastase.

关键词： Fusiform aneurysm rabbit model

Validation of a preclinical dry eye model in New Zealand white rabbits during and following topical instillation of 1% ophthalmic atropine sulfate

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Animal models and Experimental Medicine 2022年第3期5卷 266-273页

作者： Alejandra Sánchez-Ríos Elba Yadira Correa-Gallegos José Manuel Medina-Espinoza Andrea Anaid Navarro-Sanchez Oscar Olvera-Montaño Leopoldo Baiza-Durán Patricia Muñoz-Villegas Medical Affairs Department Laboratorios SophiaSA de CVZapopanJaliscoMexico

Background : The objective of this study was to validate an animal model for dry eye during and after the administration of 1% ophthalmic atropine sulfate(OAS) in New Zealand white(NZW) rabbits.Methods : OAS(1%) was applied three times per day to 30 eyes of 15 healthy NZW rabbits. Sacrifice, enucleation, and lacrimal gland removal took place on days 15, 21,and 30(OAS group). A second group(n = 5) was used as control. Clinical evaluations took place on days 3, 10, 15, 18, 21, 24 and 30. The primary endpoints were:Schirmer I test, tear break-up time(TBUT), and corneal fluorescein staining. As secondary endpoints, clinical changes including intraocular pressure, and histopathology were evaluated.Results : While OAS was administered, the Schirmer I test showed a statistically significant reduction for OAS group versus control( p model in NZW rabbits as reported in previous studies was confirmed, provided that the application of the drug is maintained throughout the intervention;it is not a viable model after OAS administration is suspended.

关键词： atropine sulfate dry eye rabbit model safety Schirmer I test TBUT

An Appreciation for the rabbit Ladderlike modeling of Radiation-induced Lung Injury with High-energy X-Ray

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Chinese Medical Journal 2015年第12期128卷 1636-1642页

作者： Xiang-Ming Fang Chun-Hong Hu Xiao-Yun Hu Xuan-Jun Yao Ping-Yan Qian Ju-Ying Zhou Jian Guo Alexander Lerner Imaging Center The First Affiliated Hospital of Soochow University Jiangsu 215006 China Imaging Center Wuxi People's Hospital Affiliated to Nanjing Medical University Jiangsu 214023 China Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions Suzhou Jiangsu 215123 China Radiotherapy Center The First Affiliated Hospital of Soochow University Jiangsu 215006 China Department of Radiology LAC+USC Medical Center University of Southern California Los Angeles CA USA

Background：To evaluate the utility of rabbit ladderlike model of radiation-induced lung injury （RILI） for the future investigation of computed tomography perfusion.Methods：A total of 72 New Zealand rabbits were randomly divided into two groups：36 rabbits in the test group were administered 25 Gy of single fractionated radiation to the whole lung of unilateral lung;36 rabbits in the control group were sham-radiated.All rabbits were subsequently sacrificed at 1,6,12,24,48,72 h,and 1,2,4,8,1 6,24 weeks after radiation,and then six specimens were extracted from the upper,middle and lower fields of the bilateral lungs.The pathological changes in these specimens were observed with light and electron microscopy;the expression of tumor necrosis factor-α （TNF-a） and transforming growth factor-βl （TGF-β1） in local lung tissue was detected by immunohistochemistry.Results：（1） Radiation-induced lung injury occurred in all rabbits in the test group.（2） Expression of TNF-a and TGF-β1 at 1 h and 48 h after radiation,demonstrated a statistically significant difference between the test and control groups （each P 〈 0.05）.（3） Evaluation by light microscopy demonstrated statistically significant differences between the two groups in the following parameters （each P 〈 0.05）：thickness of alveolar wall,density of pulmonary interstitium area （1 h after radiation）,number offibroblasts and fibrocytes in interstitium （24 h after radiation）.The test group metrics also correlated well with the time ofpostradiation.（4） Evaluation by electron microscopy demonstrated statistically significant differences in the relative amounts of collagen fibers at various time points postradiation in the test group （P 〈 0.005）,with no significant differences in the control group （P 〉 0.05）.At greater than 48 h postradiation the relative amount of collagen fibers in the test groups significantly differ from the control groups （each P 〈 0.05）,correlating well with the time postradiation （r =0.99318）.Conclusions：A consistent and reliable rabbit model of RILI can

关键词： Radiation-induced Lung Injury Radiation-induced Fibrosis Radiation Therapy rabbit model

Mechanism of Chronic Stress-induced Reduced Atherosclerotic Medial Area and Increased Plaque Instability in rabbit models of Chronic Stress

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Chinese Medical Journal 2018年第2期131卷 161-170页

作者： Ze-Mou Yu Xiao-Tao Deng Ruo-Mei Qi Lu-Yan Xiao Chong-Qing Yang Tao Gong Deoartment of Neuroloav Beiiinq Hospital National Center of Gerontology Beijing 100730 China Denartment of Radioloav. Beiiina Hospital National Center of Gerontology Beijing 100730 China The MOH'Key Laboratory of Geriatrics Beijing Hospital National Center of Gerontology Beijing 100730 China Department of Laboratory Beijing Hospital National Center of Gerontology Beijing 100730 China Department of Pathology Beijing Hospital National Center of Gerontology Beijing 100730 China

Background： Chronic stress contributes to increased risks ofatherosclerotic diseases including heart disease, stroke, and transient ischemic attack. However, its underline mechanisms are poorly understood. This study aimed to elucidate the mechanism via which chronic stress exerts its effect on atherosclerosis （AS）. Methods： Fifty male New Zealand white rabbits were used. Aortic balloon-injury model was applied. Both social stress and physical stress methods were adopted to establish chronic stress models. The lumen stenotic degree, intimal and medial areas, maximum fibrous cap thickness, and plaque contents were measured with histological sections. Proteomic methods were applied to detect protein changes in abdominal aortas to identify the specialized mediators. Real-time reverse transcription-polymerase chain reaction was used for further verification and investigation. Results： The stress rabbits exhibited lower body weight, worse fur state, more inactivity behavior, and higher serum cortisol level. Chronic stress was significantly associated with the decreased medial area and increased plaque instability, which was manifested by thinner fibrous caps, larger lipid cores, more macrophages, and new vessels but fewer smooth muscle cells and elastic fibers. After chronic stress, the apoptosis-related genes UBE2K, BAX, b）~S, Ca.v^ase 3, Caspase 9, and P53 were upregulated, and B^Z-2/BAX was down-regulated; the angiogenesis-related genes ANG and VEGF-A were also highly expressed in atherosclerotic arteries. Conclusions： rabbit models of chronic stress were successfully established by applying both social stress and physical stress for 8 weeks. Chronic stress can reduce AS tunica media and accelerate plaque instability by promoting apoptosis and neovascularization.

关键词： Atherosclerosis Chronic Stress： Plaque Stability rabbit model Tunica Media

Characteristics of a Novel model for both Atherosclerosis and Acute Myocardial Infarction in rabbit

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Characteristics of a Novel Model for both Atherosclerosis an...

Pharmacokinetic study of repaglinide floating drug delivery system in rabbits by RP-HPLC method

第十次中国中西医结合学会心血管病学术大会暨第五次江西省...

作者： Wei Shen~1,Hai-Ming Shi~1,Wei-Hu Fan~1,Xin-Ping Luo~1,Jun Zhu~1,Bo Jin~1, Jun-Jie Pan~1,Jian Li~1,Yong Li~1 1,Department of Cardiology,Huashan Hospital,Fudan University,No.12 Middle Urumqi Road,Shanghai 200040,China

Objective The role of angiogenesis in atherosclerosis and ischemic myocardium has attracted interest from opposite perspectives.However,there are no suitable models that mimic both atherosclerosis and ischemic myocardium in humans.In this study, we attempted to develop a novel model for atherosclerosis and acute myocardial infarction in rabbits in order to develop a tool for investigating pathophysiological mechanism of angiogenesis and evaluating the effect of new therapeutic drugs and interventions. Methods and Results 20 New Zealand rabbits were fed atherogenic diet for 9 weeks, and were made acute myocardial infarction by blocking coronary artery through catheter at the end of the 3rd week.Another 5 rabbits were given normal diet for 9 weeks without coronary artery blocking as the blank control group.The examinations of ECG and cardiac function,nitrotetrazolium blue chloride,H.E and SudanⅢstaining all proved myocardial infarction and atherosclerosis in the same animal model.The CD34 positive response intensity and western blot analyses indicated that angiogenesis occurred both in atherosclerosis and ischemic myocardium. Conclusions To the best of our knowledge,this is the first report of controllable rabbit model for both atherosclerosis and ischemic myocardium,which will help to study angiogenesis in humans.

关键词： angiogenesis myocardial infarction atherosclerosis rabbit model

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Journal of Chinese Pharmaceutical Sciences 2012年第2期21卷 162-168页

作者： T.Ramanjireddy D.Dhachinamoorthi K.B.Chandrasekhar Department of Pharmaceutics CES College of PharmacyKurnool 518218India Department of Pharmaceutics QIS College of PharmacyOngole 523002India Department of Chemistry JNTUAAnantapur 515002India

The present work is aimed to study the pharmacokinetic parameters of optimized repaglinide floating drug delivery system(FDDS) by 24 factorial designs,followed by comparison with a commercially available formulation.The main effects and interactions of formulation variables were studied by using normal and pareto charts.The optimized formulation shows a fickian diffusion drug release mechanism.Pharmacokinetic parameters of the designed drug delivery system were evaluated in rabbit models.Mean while a simple,specific high performance liquid chromatographic method was developed and validated as per biopharmaceutical specifications,the linearity was observed at the range of 110-550 ng/mL(r2 = 0.999).By using methanol-phosphate buffer(pH 2.5)(70:30,v/v) as mobile phase at the flow rate of 1.0 mL/min the validation shows a better retention time of 5.2 min for repaglinide.And the same validation method was used for pharmacokinetic profile analysis of repaglinide marketed products and FDDS.The comparative pharmacokinetic results such as tmax,half-life,area under the curve,mean residence times were increased significantly for the repaglinide in FDDS than the marketed product of repaglinide except Cmax and elimination rate constant.

关键词： Pharmacokinetic study Floating drug delivery system rabbit model

Bifunctional staining for ex vivo determination of area at risk in rabbits with reperfused myocardial infarction

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World Journal of Methodology 2013年第3期3卷 27-38页

作者： Yuanbo Feng Zhan-Long Ma Feng Chen Jie Yu Marlein Miranda Cona Yi Xie Yue Li Yicheng Ni Theragnostic Laboratory Department of Imaging and Pathology Biomedical Sciences Group 3000 KU Leuven Belgium Departments of Radiology the First Affiliated Hospital Nanjing Medical University Nanjing 210029 Jiangsu Province China Departments of Electronics and Information System (ELIS) Ghent University Sint-Pietersnieuwstraat 25 9000 Gent Belgium Lab of Translational Medicine Jiangsu Academy of Traditional Chinese Medicine nanjing 210028 Jiangsu Province China Radiology Section University Hospitals 3000 Leuven Belgium

AIM: To develop a method for studying myocardial area at risk(AAR) in ischemic heart disease in correlation with cardiac magnetic resonance imaging(c MRI). METHODS: Nine rabbits were anesthetized, intubated and subjected to occlusion and reperfusion of the left circumflex coronary artery(LCx) to induce myocardial infarction(MI). ECG-triggered c MRI with delayed en-hancement was performed at 3.0 T. After euthanasia, the heart was excised with the LCx re-ligated. Bifunctional staining was performed by perfusing the aorta with a homemade red-iodized-oil(RIO) dye. The heart was then agar-embedded for ex vivo magnetic resonance imaging and sliced into 3 mm-sections. The AAR was defined by RIO-staining and digital radiography(DR). The perfusion density rate(PDR) was derived from DR for the AAR and normal myocardium. The MI was measured by in vivo delayed enhancement(i DE) and ex vivo delayed enhancement(e DE) c MRI. The AAR and MI were compared to validate the bifunctional straining for cardiac imaging research. Linear regression with Bland-Altman agreement, one way-ANOVA with Bonferroni's multiple comparison, and paired t tests were applied for statistics.RESULTS: All rabbits tolerated well the surgical procedure and subsequent c MRI sessions. The openchest occlusion and close-chest reperfusion of the LCx, double suture method and bifunctional staining were successfully applied in all animals. The percentage MI volumes globally(n = 6) and by slice(n = 25) were 36.59% ± 13.68% and 32.88% ± 12.38% on i DE, and 35.41% ± 12.25% and 32.40% ± 12.34% on e DE. There were no significant differences for MI determination with excellent linear regression correspondence(r global = 0.89; r slice = 0.9) between i DE and e DE. The percentage AAR volumes globally(n = 6) and by slice(n = 25) were 44.82% ± 15.18% and 40.04% ± 13.64% with RIO-staining, and 44.74% ± 15.98% and 40.48% ± 13.26% by DR showing high correlation in linear regression analysis(r global = 0.99; r slice = 1.0). The mean differences of the two AAR measurements on Bl

关键词： Reperfused Acute myocardial infarction rabbit model Cardiac magnetic resonance imaging Oil-red-o dye Iodized oil

Selective Posterior Epiphysiodesis of the Triradiate Cartilage of the Acetabulum: Preliminary Results of an Experimental Study in rabbits

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Open Journal of Orthopedics 2016年第8期6卷 240-257页

作者： Bibiana Dello Russo Orthopaedic Surgeon Hospital Nacional de Pediatría J.P. Garrahan Buenos Aires Argentina

Background: Residual acetabular dysplasia is one of the main complications of developmental dysplasia of the hip (DDH). Without treatment, over time degenerative osteoarthritis of the joint will develop, inexorably leading to the need for joint replacement. Acetabular and/or femoral osteotomies do not avoid the appearance of osteoarthritis in a significant number of patients. The purpose of this study was to assess the possibility of provoking changes in the morphology of the acetabulum through selective epiphysiodesis of the extra-articular portion of the ilioischial arm of the triradiate cartilage, using a percutaneous cannulated screw with the guidance of an imaging intensifier in an experimental model in rabbits. Methods: In a pilot study, 3-week-old New Zealand rabbits (n = 20) were submitted to unilateral surgery of the hip while the contralateral hip of the same group was used as a control. Posterior epiphysiodesis to the triradiate cartilage of the acetabulum was performed by placement of a cannulated screw. The rabbits were followed-up until 18 weeks of life. Radiographic measurements of the hips were performed immediately postoperatively and at 12 weeks of life and before the rabbits were sacrificed at week 18. Three-dimensional computed tomography (3D-CT) scans were performed. Non-parametric tests for paired samples and the Wilcoxon test were used to compare the differences between group 1 and group 2. A p rabbit matured, the acetabulum lost concavity and depth. When comparing the median differences of the angles evaluated at 12 weeks between groups, a statistically significant difference was found in all radiographic measurements: an increase in Wiberg’s angle but a decrease in acetabular index, acetabular angle of Sharp, acetabular depth index, and acetabular anteversion. Evaluating the operated hips at 12 and 18 weeks (three months after having removed the screw) using 3D-CT, we observed a rebound effect in the

关键词： Acetabular Dysplasia Selective Epiphysiodesis rabbit model