动脉粥样硬化小型猪三磷酸腺苷结合盒转运体Al表达的变化

用贵州小香猪建立动脉粥样硬化动物模型,探讨动脉粥样硬化小型猪三磷酸腺苷结合盒转运体Al(ABCAl)表达的变化．采用血管内膜损伤法加高脂高胆固醇饲料喂养贵州小香猪,建立动脉粥样硬化动物模型．血浆总胆固醇、甘油三酯和高密度脂蛋白胆固醇的浓度均用氧化酶法测定,采用逆转录聚合酶链反应检测ABCAlmRNA水平,蛋白质印迹和免疫组织化学检测ABCAl蛋白质的表达．喂养12个月后,实验组与正常对照组比较,空腹血浆总胆固醇、甘油三酯和高密度脂蛋白胆固醇水平升高;实验组小型猪主动脉、髂动脉、颈总动脉和冠状动脉可见动脉粥样硬化斑块和脂质条纹;实验组小型猪肝组织、主动脉、小肠组织ABCAl表达上调．结果提示,采用血管内膜损伤法加高脂高胆固醇饲料喂养小型猪可建立动脉粥样硬化动物模型．动脉粥样硬化小型猪肝组织、主动脉和小肠组织ABCAl表达上调．     

动脉粥样硬化小型猪三磷酸 腺苷结合盒转运体 A1 表达的变化

用贵州小香猪建立动脉粥样硬化动物模型,探讨动脉粥样硬化小型猪三磷酸腺苷结合盒转运体 A1(ABCA1) 表达的变化 . 采用血管内膜损伤法加高脂高胆固醇饲料喂养贵州小香猪,建立动脉粥样硬化动物模型 . 血浆总胆固醇、甘油三酯和高密度脂蛋白胆固醇的浓度均用氧化酶法测定,采用逆转录聚合酶链反应检测 ABCA1mRNA 水平,蛋白质印迹和免疫组织化学检测 ABCA1 蛋白质的表达 . 喂养 12 个月后,实验组与正常对照组比较,空腹血浆总胆固醇、甘油三酯和高密度脂蛋白胆固醇水平升高;实验组小型猪主动脉、髂动脉、颈总动脉和冠状动脉可见动脉粥样硬化斑块和脂质条纹;实验组小型猪肝组织、主动脉、小肠组织 ABCA1 表达上调 . 结果提示,采用血管内膜损伤法加高脂高胆固醇饲料喂养小型猪可建立动脉粥样硬化动物模型 . 动脉粥样硬化小型猪肝组织、主动脉和小肠组织 ABCA1 表达上调 .     

ApoE~(-/-)小鼠动脉粥样硬化模型的建立

ApoE-基因敲除小鼠(ApoE-/-)经含有21%脂肪和0.15%胆固醇的高脂饲料喂食12周后进行各项血脂胆固醇水平检测,以及整体主动脉油红O染色与主动脉根部病理切片油红O染色等动脉粥样硬化病理分析。结果显示经过高脂诱导的ApoE-/-小鼠的血浆总胆固醇和甘油三酯水平均比未经饮食诱导的ApoE-/-小鼠、经同样饮食处理的野生型小鼠以及未经处理的野生型小鼠均显著升高(P0.05);低密度脂蛋白-胆固醇水平与野生型(正常饮食组和高脂组)相比升高了近3倍多;高脂诱导ApoE-/-小鼠的主动脉斑块面积占整体主动脉面积的65%,显著高于ApoE-/-小鼠的正常饮食组(21%)(P0.05),同时主动脉根部的血管壁明显增厚,管腔变窄。实验结果表明通过高脂饲料饮食诱导,成功建立了动脉粥样硬化模型小鼠,可为下游的药物筛选、基因治疗以及动脉粥样硬化机理的体内研究提供理想的实验材料。     

短链脂肪酸丁酸抑制动脉粥样硬化形成及其分子机制

本研究通过观察丁酸对动脉粥样硬化斑块形成以及肠道组织结构和功能的影响,探讨丁酸防治动脉粥样硬化的效应及可能机制.选取8周龄雄性载脂蛋白E基因敲除(apolipoprotein E-knockout,ApoE-/-)小鼠,随机分成对照组(高脂高胆固醇饲料+饮水中给予200 mmol/L氯化钠,n = 10)和丁酸组(高脂...     

液氮冻伤术建立动脉粥样硬化破裂斑块及血栓模型

目的创建一种操作简单、经济实用的动脉粥样硬化（AS）破裂斑块及血栓动物模型。方法21只雄性纯种新西兰白兔随机分为两组：液氮冻伤＋高脂喂养组（A组=11只）和高脂喂养组（B组=10只）。A组实施右颈总动脉内膜液氮冻伤术结合高脂饲料喂养,B组单纯给予高脂饲料喂养。8周末以液氮激发斑块破裂,激发前后分别采血检测血脂、hsC-RP、MMP-9及PAI-1水平;激发48h后处死所有动物,取出右颈总动脉作HE染色及免疫组化染色等,光镜及电镜观察破裂斑块及血栓形成情况。结果8周后兔血脂水平明显升高;激发后血浆hsC-RP、MMP-9及PAI-1均明显升高;所有A组兔子的右颈总动脉均可见AS破裂斑块及血栓形成,而B组兔子未见斑块或血栓形成;所建立的破裂斑块在组织结构、细胞构成、生长特征和脂质沉积方面与人类斑块相似。结论液氮冻伤术能简便、快速、高效地建立AS破裂斑块及血栓模型,从而为研究人类AS破裂斑块及血栓形成的机理和药物干预治疗提供了一种新型动物模型。     

2型糖尿病气阴两虚病证结合动物模型的制备及评价指标的建立

目的 建立2型糖尿病气阴两虚型病证结合动物模型及评价指标.方法 SD大鼠48只随机分为空白组、病证模型组和高糖高脂组,空白组喂饲普通饲料,其余两组喂饲高脂饲料.饲养4周后,病证模型组大鼠禁食12 h腹腔注射链脲佐菌素(STZ)40 mg/kg,1周后测定大鼠空腹血糖值大于11.1 mmol/L视为糖尿病造模成功,继续饲...     

动脉粥样硬化基因工程小鼠模型

建立可靠的动脉粥样硬化动物模型对于探明其病因、发病机制及防治药物的开发均具有重要的意义。本文介绍了载脂蛋白、脂质代谢有关的受体、脂质代谢有关的酶和转运蛋白等十几种动脉粥样硬化相关基因的基因工程小鼠模型的特点及应用。     

基于生物芯片探讨高脂饮食对动脉粥样硬化小鼠基因组DNA甲基化的影响

目的:采用DNA甲基化芯片技术探讨高脂饮食对Apo E-/-小鼠动脉粥样硬化模型全基因组DNA甲基化的影响。方法:30只雄性Apo E-/-小鼠随机分为正常组与高脂组,每组15只,正常组给予正常饲料喂养,高脂组给予高脂饲料喂养。16周后,测其血脂、血清同型半胱氨酸水平(Hcy)水平、血清DNA甲基化与血清DNA甲基化转移酶(DNMTs)水平;采用DNA甲基化芯片检测两组小鼠主动脉组织全基因组甲基化情况。结果:与正常组相比,高脂组小鼠血清CHOL、TG、LDL-C均显著升高,HDL-C显著下降;血清DNA甲基化水平与血清DNA甲基化转移酶(DNMTs)水平均显著升高。甲基化芯片结果显示:与正常组相比,高脂组主动脉全基因组中共有875个基因甲基化发生改变,差异具有统计学意义(P0.05),其中高甲基化基因数目496,占总数56.69%;低甲基化基因数目379,占总数的43.31%。结论:高脂饲料可升高主动脉基因组甲基化水平,降低基因组的表达,可能是Apo E-/-小鼠容易形成动脉粥样硬化的机制之一。     

牛磺酸抗小鼠动脉粥样硬化的研究

为了探讨牛磺酸抗小鼠动脉粥样硬化的影响及可能机制,将C57BL/6J小鼠分成五组,正常对照组给予基础饲料喂养,高脂组给予高脂饲料,牛磺酸组分别给予含1.0%、3.0%和5.0%牛磺酸的高脂饲料,实验时间为90d。结果表明,高脂组小鼠主动脉内膜和肝脏发生了粥样硬化病变和脂肪变性,而牛磺酸组病变程度随剂量增大而减轻。高脂组较正常对照组血清及肝脏甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-c)、动脉硬化指数(AI)显著升高,高密度脂蛋白胆固醇(HDL-c)显著降低;牛磺酸组较高脂组显著改善。可见牛磺酸可通过改善脂质代谢紊乱发挥抗动脉粥样硬化的作用。     

小型猪动脉粥样硬化模型研究进展

小型猪因在动脉解剖、生理等方面与人类十分相似,是目前研究动脉粥样硬化(atherosclerosis,AS相关疾病最理想的模型。至今已有多种可以模拟小型猪AS模型的方法公布,除传统的高脂饲料+球囊拉伤外,还包括新方法如基因编辑诱导自发性高脂血症、冠脉壁局部注射脂质或炎症因子等。但目前尚无成熟、公认的小型猪冠状动脉粥样硬化模型。造模周期长、成功率低、花费高等是制约小型猪动物模型研究的瓶颈所在。现就适合造模的小型猪的品种、造模方法进行综述。     

痔疮动物模型制作方法研究进展

近年来,在兔、大鼠、小鼠和犬等动物种属成功地建立了巴豆油、醋酸、感染与创伤诱导的痔疮动物模型,每种动物模型各有优缺点,应用合理的动物模型能更好地开展痔的实验和临床研究。随着治痔药物的深入研究,动物模型有很好发展和应用,本文综述了痔疮动物模型制作方法研究进展。     

Estimating heritabilities and genetic correlations: comparing the 'animal model' with parent-offspring regression using data from a natural population

Quantitative genetic parameters are nowadays more frequently estimated with restricted maximum likelihood using the 'animal model' than with traditional methods such as parent-offspring regressions. These methods have however rarely been evaluated using equivalent data sets. We compare heritabilities and genetic correlations from animal model and parent-offspring analyses, respectively, using data on eight morphological traits in the great reed warbler (Acrocephalus arundinaceus). Animal models were run using either mean trait values or individual repeated measurements to be able to separate between effects of including more extended pedigree information and effects of replicated sampling from the same individuals. We show that the inclusion of more pedigree information by the use of mean traits animal models had limited effect on the standard error and magnitude of heritabilities. In contrast, the use of repeated measures animal model generally had a positive effect on the sampling accuracy and resulted in lower heritabilities; the latter due to lower additive variance and higher phenotypic variance. For most trait combinations, both animal model methods gave genetic correlations that were lower than the parent-offspring estimates, whereas the standard errors were lower only for the mean traits animal model. We conclude that differences in heritabilities between the animal model and parent-offspring regressions were mostly due to the inclusion of individual replicates to the animal model rather than the inclusion of more extended pedigree information. Genetic correlations were, on the other hand, primarily affected by the inclusion of more pedigree information. This study is to our knowledge the most comprehensive empirical evaluation of the performance of the animal model in relation to parent-offspring regressions in a wild population. Our conclusions should be valuable for reconciliation of data obtained in earlier studies as well as for future meta-analyses utilizing estimates from both traditional methods and the animal model.     

子痫前期动物模型的研究进展

子痫前期是一种非常严重的妊娠疾病,主要症状有高血压、蛋白尿、内皮功能障碍、肾小球血管内皮细胞增生以及滋养层细胞浸润不足等,动物模型是研究本病发病机理与开发诊治手段的主要工具.长期以来,针对子痫前期主要症状已经建立了多种动物模型,但不同的动物模型各有优缺点,至今仍没有一个理想的子痫前期动物模型,这也是子痫前期病因不明和缺乏有效治疗手段的主要原因之一.本文就已有的模型进行了归纳总结,旨在为不同研究需要而选择合适的模型,并为开发更为理想的子痫前期动物模型提供参考.     

Parameter redundancy in discrete state‐space and integrated models

Discrete state‐space models are used in ecology to describe the dynamics of wild animal populations, with parameters, such as the probability of survival, being of ecological interest. For a particular parametrization of a model it is not always clear which parameters can be estimated. This inability to estimate all parameters is known as parameter redundancy or a model is described as nonidentifiable. In this paper we develop methods that can be used to detect parameter redundancy in discrete state‐space models. An exhaustive summary is a combination of parameters that fully specify a model. To use general methods for detecting parameter redundancy a suitable exhaustive summary is required. This paper proposes two methods for the derivation of an exhaustive summary for discrete state‐space models using discrete analogues of methods for continuous state‐space models. We also demonstrate that combining multiple data sets, through the use of an integrated population model, may result in a model in which all parameters are estimable, even though models fitted to the separate data sets may be parameter redundant.     

Animal models of gastrointestinal inflammation and cancer

Inflammation and cancer are the two major disorders in the gastrointestinal tract. They are causally related in their pathogenesis. It is important to study animal models' causal relationship and, in particular, to discover new therapeutic agents for such diseases. There are several criteria for these models in order to make them useful in better understanding the etiology and treatment of the said diseases in humans. In this regard, animal models should be similar as possible to human diseases and also be easy to produce and reproducible and also economic to allow a continuous replication in different laboratories. In this review, we summarize the various animal models for inflammatory and cancerous disorders in the upper and lower gastrointestinal tract. Experimental approaches are as simple as by giving a single oral dose of alcohol or other noxious agents or by injections of multiple dosages of ulcer inducing agents or by parenteral administration or in drinking water of carcinogens or by modifying the genetic makeups of animals to produce relatively long-term pathological changes in particular organs. With these methods they could induce consistent inflammatory responses or tumorigenesis in the gastrointestinal mucosa. These animal models are widely used in laboratories in understanding the pathogenesis as well as the mechanisms of action for therapeutic agents in the treatment of gastrointestinal inflammation and cancer.     

Pedigree-free animal models: the relatedness matrix reloaded

Animal models typically require a known genetic pedigree to estimate quantitative genetic parameters. Here we test whether animal models can alternatively be based on estimates of relatedness derived entirely from molecular marker data. Our case study is the morphology of a wild bird population, for which we report estimates of the genetic variance-covariance matrices (G) of six morphological traits using three methods: the traditional animal model; a molecular marker-based approach to estimate heritability based on Ritland's pairwise regression method; and a new approach using a molecular genealogy arranged in a relatedness matrix (R) to replace the pedigree in an animal model. Using the traditional animal model, we found significant genetic variance for all six traits and positive genetic covariance among traits. The pairwise regression method did not return reliable estimates of quantitative genetic parameters in this population, with estimates of genetic variance and covariance typically being very small or negative. In contrast, we found mixed evidence for the use of the pedigree-free animal model. Similar to the pairwise regression method, the pedigree-free approach performed poorly when the full-rank R matrix based on the molecular genealogy was employed. However, performance improved substantially when we reduced the dimensionality of the R matrix in order to maximize the signal to noise ratio. Using reduced-rank R matrices generated estimates of genetic variance that were much closer to those from the traditional model. Nevertheless, this method was less reliable at estimating covariances, which were often estimated to be negative. Taken together, these results suggest that pedigree-free animal models can recover quantitative genetic information, although the signal remains relatively weak. It remains to be determined whether this problem can be overcome by the use of a more powerful battery of molecular markers and improved methods for reconstructing genealogies.     

Calibrated Forceps Model of Spinal Cord Compression Injury

Compression injuries of the murine spinal cord are valuable animal models for the study of spinal cord injury (SCI) and spinal regenerative therapy. The calibrated forceps model of compression injury is a convenient, low cost, and very reproducible animal model for SCI. We used a pair of modified forceps in accordance with the method published by Plemel et al. (2008) to laterally compress the spinal cord to a distance of 0.35 mm. In this video, we will demonstrate a dorsal laminectomy to expose the spinal cord, followed by compression of the spinal cord with the modified forceps. In the video, we will also address issues related to the care of paraplegic laboratory animals. This injury model produces mice that exhibit impairment in sensation, as well as impaired hindlimb locomotor function. Furthermore, this method of injury produces consistent aberrations in the pathology of the SCI, as determined by immunohistochemical methods. After watching this video, viewers should be able to determine the necessary supplies and methods for producing SCI of various severities in the mouse for studies on SCI and/or treatments designed to mitigate impairment after injury.     

An experiment on animal re-identification from video

In the face of the global concern about climate change and endangered ecosystems, monitoring individual animals is of paramount importance. Computer vision methods for animal recognition and re-identification from video or image collections are a modern alternative to more traditional but intrusive methods such as tagging or branding. While there are many studies reporting results on various animal re-identification databases, there is a notable lack of comparative studies between different classification methods. In this paper we offer a comparison of 25 classification methods including linear, non-linear and ensemble models, as well as deep learning networks. Since the animal databases are vastly different in characteristics and difficulty, we propose an experimental protocol that can be applied to a chosen data collections. We use a publicly available database of five video clips, each containing multiple identities (9 to 27), where the animals are typically present as a group in each video frame. Our experiment involves five data representations: colour, shape, texture, and two feature spaces extracted by deep learning. In our experiments, simpler models (linear classifiers) and just colour feature space gave the best classification accuracy, demonstrating the importance of running a comparative study before resorting to complex, time-consuming, and potentially less robust methods.     

子宫内膜异位症动物模型研究进展

为更好的把动物模型应用于子宫内膜异位症的病因、发病机制及治疗等方面的研究,本文将对子宫内膜异位症实验动物的选择、传统动物模型、新型特殊动物模型的构建方法及优缺点进行综述,以期为子宫内膜异位症疾病动物模型的研究提供参考。     

Method used to establish a large animal model of drug-induced acute kidney injury

Acute kidney injury is a serious health hazard disease due to its complex etiology and lack of effective treatments, resulting in high medical costs and high mortality. At present, a large number of basic research studies on acute kidney injury have been carried out. However, acute kidney injury models established in rodents sometimes do not simulate the course of human disease well. Research in large animal models of acute kidney injury is relatively rare, and methods to build a mature model of acute kidney injury have failed. Because its kidney anatomy and morphology are very similar to those in humans, the mini pig is an ideal animal in which to model kidney disease. Nephrotoxic drug-induced acute kidney injury has a high incidence. In this study, we established models of acute kidney injury induced by two drugs (gentamicin and cisplatin). Finally, the model of cisplatin-induced acute kidney injury was developed successfully, but we found the model of gentamycin-induced acute kidney injury was not reproducible. Compared to other models, these models better represent acute kidney injury caused by antibiotics and chemotherapeutic drugs and provide a basis for the study of new treatments for acute kidney injury in a large animal model.