兔膝骨关节炎合并骨质疏松症动物模型的建立

背景：临床发现同时患有骨质疏松症和骨关节炎患者占相当大的比例,而且目前对骨质疏松与骨关节炎相互关系的认识不一致。 目的：建立骨关节炎合并骨质疏松症的动物模型。 方法：将14只新西兰大白兔随机等分为模型组和正常组。模型组新西兰大白兔行双侧卵巢切除,正常组新西兰大白兔不作任何处理。 结果与结论：去除卵巢10周后,模型组大白兔关节软骨出现明显的退变,血清雌二醇、股骨骨密度水平较正常组显著下降(P < 0.01),而关节软骨Mankin评分比正常组显著增高(P < 0.01);且软骨Mankin评分与骨密度和血清雌二醇呈负相关,而骨密度与血清雌二醇水平呈正相关,表明实验成功建立了兔膝骨关节炎合并骨质疏松症动物模型。     

骨关节炎的转基因动物模型

背景：近年来随着转基因技术的发展,出现了骨关节炎的转基因动物模型,表明不同基因的缺失与突变都可能导致骨关节炎,这将为骨关节炎的药物筛选试验和治疗提供新方案。 目的：对骨关节炎的转基因动物模型的构建及其相关机制进行概述,为防治骨关节炎奠定理论基础。 方法：第一作者应用计算机检索1995/2010 PubMed数据库相关文章,检索词为“transgenic animal models,Osteoarthritis”,并限定文章语言种类为English。同时计算机检索2000/2010 中国知网数据库相关文章,检索词为“转基因动物模型,骨关节炎”并限定文章语言种类为中文。共检索到文章158 篇,最终纳入22篇。 结果与结论：骨关节炎转基因动物模型在研究骨关节炎起始机制、关节软骨生化改变和防治效果的比较等方面具有明显优势;排除了手术创伤及炎症对骨关节炎模型软骨、滑膜的生化代谢的影响;同时也减轻了模型动物的痛苦。为药物筛选试验和治疗提供新方案。     

红姜提取物保护早期膝骨关节炎模型大鼠的关节软骨

BACKGROUND: Studies have reported that the combined use of ginger extract to reduce the levels of serum pro-inflammatory cytokines, including interleukin-1β, interleukin-6, tumor necrosis factor-α, is related to the reduction of cartilage injury in knee osteoarthritis. OBJECTIVE: To observe the protective effect of red ginger extract on articular cartilage and the expression of serum interleukin-1β, interleukin-6, tumor necrosis factor-α and cartilage tissue type II collagen α1 mRNA in rats with early knee osteoarthritis, and to explore the protective effect of red ginger extract on articular cartilage of rats with early knee osteoarthritis and its possible mechanism. METHODS: Fifty SPF Sprague-Dawley rats were randomly divided into blank group, model group, low-dose red ginger, high-dose red ginger and positive control group (n=10 per group). Except for the blank group, the rats in the other four groups were used to prepare knee osteoarthritis models by intraarticular injection of 4% papain 0.2 mL+0.03 mol/L L-cysteine mixed solution. The rats in the blank and model groups were fed routinely, and the low-dose red ginger, high-dose red ginger and positive control groups were given 50 mg/kg red ginger extract aqueous solution, 100 mg/kg red ginger extract aqueous solution and 18 mg/kg celecoxib capsule aqueous solution respectively. All the interventions were conducted once a day, for 4 continuous weeks. Four weeks after treatment, the rats in each group were killed and the knee joints were stained with safranin O-fast green. The articular cartilage was scored by Mankin scoring. The expression levels of interleukin-1β, interleukin-6, tumor necrosis factor-α in serum and type II collagen α1 mRNA in cartilage were detected. The study protocol was approved by the Animal Ethics Committee of Guangzhou University of Chinese Medicine, with an approval No. 20190917002. RESULTS AND CONCLUSION: The pathological section of knee cartilage showed that there was cartilage matrix loss in the model and each treatment group, and the Mankin score of each treatment group was significantly higher than that of the blank group (P < 0.05) and lower than that of the model group (P < 0.05). There was no significant difference between the high-dose group and the positive control group (P > 0.05), but the scores of the two groups were lower than that of the low-dose group. The levels of interleukin-1β, interleukin-6, and tumor necrosis factor-α were upregulated in the positive control group, high-dose red ginger group and low-dose red ginger group compared with the blank group and down-regulated compared with the model group (P < 0.05). Moreover, and the levels of these cytokines were ranked as follows: positive control group < high-dose red ginger group < low-dose red ginger group (P < 0.05). The level of type II collagen α1 mRNA in cartilage showed no significant difference between the blank group and the high-dose red ginger group and the positive control group (P > 0.05), whereas the expression of type II collagen α1 mRNA was significantly increased in the model group and low-dose red ginger group compared with the other three groups (P < 0.05). To conclude, red ginger extract may protect the articular cartilage of knee osteoarthritis by inhibiting interleukin-1β, interleukin-6, and tumor necrosis factor-α, thereby delaying the development of knee osteoarthritis. Compared with the low-dose group, high-dose red ginger extract has better anti-inflammatory effect. © 2021, Journal of Clinical Rehabilitative Tissue Engineering Research. All rights reserved.     

踝关节骨关节炎动物模型构建的研究与进展

背景：踝关节骨关节炎作为极大影响患者生活质量的疾病,正越来越得到人们重视。踝骨关节炎的临床及实验研究尚不及膝关节研究完备,目前缺乏关于动物模型较为系统的综述。目的：探讨踝骨关节炎各实验模型的造模方法,阐述各模型的特点,为踝骨关节炎的实验研究的改进提供理论依据。方法：检索2009-2022年中国知网、万方数据平台、维普期刊平台、PubMed、Embase数据库发表的相关文献,中文检索词“踝关节;骨关节炎;动物模型;创伤后骨关节炎”,英文检索词“Ankle Joint;Osteoarthritis;Animal models;Post-Traumatic Osteoarthritis”,共纳入49篇文章进行系统性综述。结果与结论：(1)踝骨关节炎的动物模型中,对于创伤性关节炎的造模方式包括慢性踝关节不稳模型和关节内骨折模型;非创伤性动物模型的造模方式包括关节内药物注射诱导模型、软骨萎缩模型、关节衰老模型以及特定品系骨关节炎易感物种的自发性骨关节炎模型。(2)虽然创伤性踝骨关节炎的发病率很高,但与膝骨关节炎相比,目前对于踝骨关节炎的研究相当有限。基于踝关节与膝关节结构及关节特性的差异,膝关节...     

自制脂肪乳剂灌胃与普通高脂饲料喂养建立家兔高脂血症动物模型的比较

目的比较采用自制脂肪乳剂灌胃和普通高脂饲料喂养两种方法建立家兔高脂血症动物模型的效果。方法40只家兔按随机数字表分为自制脂肪乳剂灌胃组（n=20）和高脂饲料喂养组（n=20）,分别给予自制脂肪乳剂灌胃连续2周和高脂饲料喂养连续4周。所有动物分别在实验前、后测定血清总胆固醇（TC）、三酰甘油（TG）、载脂蛋白A1（ApoAl）、ApoB,血浆血栓素B2（TXB2）、6-酮-前列腺素F_1α（6-keto-PGF_1α）、内皮素（ET）、红细胞膜总胆醇（M-TC）、红细胞膜流动性（M-Flu）、红细胞丙二醛（E-MDA）、红细胞超氧化物歧化酶（E-SOD）水平,实验结束时取主动脉组织进行病理检查。结果实验后两组家兔TC、TG、ApoB、TXB2、ET、E-MDA水平较实验前升高,ApoAl、6-keto-PGF_1α、M-Flu、E-SOD水平较实验前降低（均P〈0．05）;而M-TC水平差异无统计学意义（均P〉0．05）。实验前、后两组同一指标组间比较,差异均无统计学意义（均P〉0．05）。病理检查显示两组动物主动脉组织均出现动脉粥样硬化早期改变。结论两种方法均可以成功建立高脂血症动物模型,采用自制脂肪乳剂灌胃建立高脂血症动物模型的方法具有可行性。     

早期创伤性膝骨关节炎动物模型构建方案的比较

背景：现有骨关节炎的有创造模方法包括前交叉韧带横断手术和前交叉韧带横断联合内侧半月板前角切除手术,前交叉韧带横断术后需要过量运动,而完整切除内侧半月板前角可能造成副损伤并增加造模结果的差异性,对术者手术技巧要求较高。目的：对传统的骨关节炎有创造模手段进行改良和简化,并比较不同方案在无高负荷运动环境下的造模效果。方法：采用随机数字表法将48只SD大鼠分为4组,每组12只：假手术组完全暴露左侧后肢膝关节腔后缝合关节腔及皮肤;横断组、横断+切除组、横断+撕裂组左侧后肢分别进行前交叉韧带横断手术、前交叉韧带横断联合内侧半月板前角切除手术、前交叉韧带横断联合内侧半月板前角撕裂手术。术后4周取膝关节标本,进行大体、X射线片、CT扫描、病理组织切片观察及PCR检测。结果与结论：(1)大体观察：横断组可见半月板处轻度磨损;横断+撕裂组可见外侧髁关节面严重磨损、内侧髁关节面轻度磨损、半月板严重磨损,内侧半月板全层磨损;横断+切除组可见外侧髁关节面严重磨损、内侧髁关节面轻度磨损、半月板内侧前角缺如,半月板磨损面积> 50%;(2)X射线片与CT扫描：4组无明显差异,其中3个手术组可见胫骨前移,横断+...     

沙浴治疗兔膝骨关节炎的实验研究

目的：研究沙浴对兔膝关节骨性关节炎(osteoarthritis OA)关节周围血流、膝关节滑膜及软骨的病理改变的影响，为中老年人膝骨关节炎的沙浴治疗提供依据。方法：青紫兰兔15只，成功建立OA动物模型13只，其中12只随机分成自由活动组(A)，自由活动加沙疗组(B)，健侧关节沙疗对照组(C)。在平均气温32℃情况下，将模型兔下半部分掩埋在干燥的40～50℃的海沙中，1次25～30min，1次／d。观察沙疗后即时的膝关节周围血流情况，以及经过沙疗10d和20d后膝关节滑膜及软骨的病理改变。结果：沙疗后患侧膝关节活动改善，膝关节周围血管内血流明显增加，膝关节滑膜细胞层次逐渐减少、炎症细胞明显减少，但软骨细胞退变改善在光学显微镜下不明显。结论：沙疗能增加治疗部位的血流，改善局部血液循环，促进炎症的消退，对正常关节无不利影响。     

心脏骤停动物模型的动物和实验方法选择

目的：在现代心肺脑复苏研究中心脏骤停模型的动物和实验方法选择十分重要。目前模型建立的方法众多，标准不一，模型复制率较低，给实验研究带来困难。Utstein指南的提出有助于心肺脑复苏(CPCR)研究报告的标准化，其研究结果便于相互比较。本文根据相关文献和我们的实验经验，综述现有常见几种心肺脑复苏动物模型的动物和实验方法的选择特点。     

短暂肾缺血建立急性肾功能衰竭动物模型

目的:建立更加符合临床实际的以肾血流减少为特征的急性肾功能衰竭(ARF)动物模型。方法:家兔双侧肾动脉不完全结扎造成肾缺血,20 min后恢复肾血流。检测动物在肾动脉不完全结扎前、后及恢复血流后的尿量、血清肌酐、电解质、血气分析并做肾脏病理学检查。结果:肾血流减少后,动物尿量明显减少,而血清肌酐水平显著升高;同期血清钾水平升高,pH降低,HCO3-及BE明显减少。恢复肾血流后尿量增多并逐步趋向正常;至恢复血流1 h时血清肌酐水平已降至正常,但代谢性酸中毒持续发展,血清钾水平降低后又有所回升。缺血20 min及恢复血流1 h和5 h的兔肾病理检查无明显改变。结论:双侧肾动脉不完全结扎法复制出的动物模型具有ARF的多重表现和功能性ARF的特点,体现了肾血流因素在ARF发生及治疗方面的临床意义,可供教学和科研参考。     

动脉瘤动物模型的研究进展

颅内动脉瘤是神经外科常见疾病,致死率和致残率都很高.探讨动脉瘤的形态、病生理、演变过程对临床治疗具有重要意义.而这些研究都依赖于建立可信的动脉瘤模型.本文对建立动脉瘤模型的几种方法进行了比较评述.     

Development of animal models of aging at the national institute on aging

The suitability of various animal species as experimental models of aging has been a continuing concern of the National Institute on Aging (NIA) for over 20 years. The history of the decisions made by NIA in providing aged animals for research may be helpful to individual investigators seeking to understand why certain models are available and which of them to choose for their work.     

Pathogenetic elements of hepatitis E and animal models of HEV infection

The pathogenesis of HEV infection responsible for liver pathology and clinical disease is not well understood. The main target for the virus is the hepatocyte, where it replicates and is released to bile and gastrointestinal tract. Viremia is regularly seen during the virus replication. The exact mechanism of hepatocytic death is uncertain. In experimentally infected non-human primates, the peak of liver lesions, measured by alanine aminotransferase activity elevation, is concordant with the virus disappearance from stool at the time of dynamic humoral immune response; the role of cellular immunity has not been researched adequately, especially HEV-specific immune response in the liver.Non-human primates (chimpanzees, rhesus and cynomolgus macaques) are most widely used animal models for the study of HEV infection, its pathogenesis and vaccine trials. Several other animal models including pigs, rabbits and chickens have recently been established for the study of various aspects of HEV infection. Infectivity studies in susceptible primates were of significance in molecular studies of the virus itself. Preclinical vaccine trials with the use of various recombinant HEV capsid proteins and viral DNA established basic platform for formulation of HEV vaccine applied in HEV-endemic regions (China, Nepal).     

Suggested guidelines for the housing and husbandry of rodents for aging studies

The available published guidelines for the housing of rodents are reviewed, and assessments are made with regard to whether the data on which these guidelines are based appear to be sound. Ambient air temperature, relative humidity, lighting levels and photoperiods, sound levels, cage sizes, and ventilation rates are discussed, and a summary is provided covering the relationship between these and other factors and the well-being of laboratory rats and mice exposed to such conditions.     

Cytochemical characteristics of hematopoietic cells of laboratory animals

The cytochemical distribution of alkaline and acid phosphatases, -naphthylacetate esterase, peroxidase, lipids, and glycogen was determined in bone marrow and peripheral blood cells of noninbred albino rats and guinea pigs. The intensity of the reaction was assessed by Kaplow's method. The cytoenzymic spectrum of the hematopoietic cells and the character of changes in their metabolism during cell differentiation and maturation were established. Quantitative specific differences were found in the content of chemical substances in the blood and bone marrow cells of rats and guinea pigs.Medical Institute, Tomsk. (Presented by Academician of the Academy of Medical Sciences of the USSR D. D. Yablokov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 81, No. 5, pp. 612–614, May, 1976.     

两种脑出血动物模型的AQP4表达与磁共振成像的比较研究

目的比较两种脑出血(ICH)动物模型磁共振成像(MRI)的差异,并对其分子机制进行探讨。方法将胶原酶和自体血注入大鼠尾状核建立脑出血模型,分别于术后6h、12h、1d、2d、3d和7d进行磁共振成像扫描,观察两组脑出血模型血肿体积的大小;运用干湿重法、伊文思蓝(EB)测定法和免疫印迹分别检测两组脑出血模型的脑含水量(BWC)、血脑屏障(BBB)通透性和AQP4的表达变化。结果胶原酶模型组的血肿体积在脑出血后1d达到最大并持续至3d,自体血组的血肿体积在12h达到最大;胶原酶模型组的BWC在1d达到高峰并持续至3d,而自体血组BWC在2d逐渐降低;胶原酶模型组的EB含量在12h达到高峰并持续至2d,而自体血组EB含量在1d逐渐下降;两组模型的AQP4表达量在6h开始升高,1d达到高峰,2d逐渐降低。两组模型比较具有统计学差异(P<0.05)。结论胶原酶对BBB和细胞外基质的破坏以及AQP4的表达变化是两组脑出血模型血肿体积出现差异的重要原因。     

Personal models of osteoarthritis and their relation to self-management activities and quality of life

We examined the personal models of osteoarthritis (OA) of 61 patients over 60 years of age. Models were elicited using a structured interview. Shared beliefs included perceiving OA as a serious, painful, chronic, and incurable condition that can be managed by recommended medical treatment. Considerable individual differences were found on six personal-model constructs: Symptoms, Seriousness, Cause, Control, Helpfulness of Treatment, and Negative Feelings about Treatment. The constructs of Symptoms and Seriousness were consistently related to a variety of important outcomes. For example, participants with higher scores on Symptoms and Seriousness reported higher levels of self-management (both concurrently and prospectively), reported more utilization of medical services, and experienced a poorer quality of life. The implications for the design of health-education materials and for patient-provider interactions are discussed.     

Transgenic animal models: new avenues in cardiovascular physiology

 Application of molecular genetic tools to inherited cardiovascular disorders has provided important insights into the molecular mechanisms underlying cardiomyopathies, arrhythmias, blood pressure regulation, and atherosclerosis. In addition, alteration of gene expression has been observed under common cardiovascular conditions such as cardiac hypertrophy and heart failure. Recent advances in transgenic and gene-targeting approaches allow a sophisticated manipulation of the mouse genome by gene addition, gene deletion, or gene modifications. These transgenic models enable the dissection of in vivo pathways responsible for these complex disease phenotypes. This review describes tissue-specific promoters suitable for targeting candidate genes to the cardiovascular system as well as a number of valuable transgenic animal models of blood pressure regulation, atherogenesis, defects in the coagulation system, cardiac hypertrophy, myocarditis, cardiomyopathies, and heart failure. Limitations and difficulties associated with these transgenic approaches are discussed. Animal models which may provide a basis for future gene therapy of cardiovascular diseases are introduced. Finally, methods are described to regulate the spatial and temporal expression level of a transgene, to inactivate a target gene in a tissue-specific manner, and to introduce specific mutations into the genome. These recent advances in transgenic technology are expected to have a considerable impact on cardiovascular research in the near future. Received: 1 February 1996 / Accepted: 13 August 1996