Application of Modeling Drugs in Animal Models of Chemical Phlebitis: Review

Objective: This review aims to determine the impact of different drugs and methods on the successful establishment of an animal model for chemical phlebitis (CP). Design: Search the Cochrane Library, ProQuest Academic Journal Library, PubMed, Web of Science, Ovid, Embase, CINAHL complete (EESCO) and other related databases to determine the literature. Screen out articles consistent with this review and summarize them. Results: Since the establishment of the database, a total of 1463 articles have been retrieved. After reading the title, abstract and full text, and excluding non-related and duplicate articles, 22 reports were finally included. Among them, there are 8 articles using different medication methods to compare the effects of establishing a CP model. The included articles explored the effects of different animal models, drug types, and their dose, concentration, speed, and time on the CP model. Conclusion: The factors of dose, concentration and time were positively correlated with the incidence of CP. The effect of speed factors on CP and the results of different animal models are inconsistent. It requires further research in the future.

Characterization and validation of a chronic retinal neovascularization rabbit model by evaluating the efficacy of anti-angiogenic and anti-inflammatory drugs

AIM:To establish a rabbit model with chronic condition of retinal neovascularization(RNV)induced by intravitreal(IVT)injection of DL-2-aminoadipic acid(DL-AAA),a retinal glial(Mül er)cell toxin,extensive characterization of DL-AAA induced angiographic features and the suitability of the model to evaluate anti-angiogenic and anti-inflammatory therapies for ocular vascular diseases.METHODS:DL-AAA(80 mmol/L)was administered IVT into both eyes of Dutch Belted rabbit.Post DL-AAA delivery,clinical ophthalmic examinations were performed weekly following modified Mc Donald-Shadduck Scoring System.Color fundus photography,fluorescein angiography(FA),and optical coherence tomography(OCT)procedures were performed every 2 or 4 wk until stable retinal vascular leakage was observed.Once stable retinal leakage(12 wk post DL-AAA administration)was established,anti-vascular endothelial growth factor(VEGF)(bevacizumab,ranibizumab and aflibercept)and anti-inflammatory(triamcinolone,TAA)drugs were tested for their efficacy after IVT administration.Fluorescein angiograms were scored before and after treatment following a novel grading system,developed for the DL-AAA rabbit model.RESULTS:Post DL-AAA administration,eyes were presented with moderate to severe retinal/choroidal inflammation which was accompanied by intense vitreous flare and presence of inflammatory cells in the vitreous humor.Retinal hemorrhage was restricted to the tips of neo-retinal vessels.FA revealed maximum retinal vascular leakage at 2 wk after DL-AAA injection and then persisted as evidenced by stable mean FA scores in weeks 8 and 12.Retinal vascular angiographic and tomographic features were stable and consistent up to 36 mo among two different staggers induced for RNV at two different occasions.Day 7,mean FA scores showed that 1μg/eye of bevacizumab,ranibizumab,aflibercept and 2μg/eye of TAA suppress 65%,90%,100%and 50%retinal vascular leakage,respectively.Day 30,bevacizumab and TAA continued to show 66%and 44%suppression while ranibizumab effect was becoming less effective(68%).In contrast,aflibercept was still able to fully(100%)suppress vascular leakage on day 30.On day 60,bevacizumab,ranibizumab and TAA showed suppression of 7%,12%,and 9%retinal vascular leakage,respectively,however,aflibercept continued to be more effective showing 50%suppression of vascular leakage.CONCLUSION:The DL-AAA rabbit model mimics RNV angiographic features like RNV and chronic retinal leakage.Based on these features the DL-AAA rabbit model provides an invaluable tool that could be used to test the therapeutic efficacy and duration of action of novel anti-angiogenic formulations,alone or in combination with anti-inflammatory compounds.

Breast cancer animal models and applications

Breast cancer is the most common malignancy in women. Basic and translational breast cancer research relies heavily on experimental animal models. Ideally, such models for breast cancer should have commonality with human breast cancer in terms of tumor etiology, biological behavior,pathology, and response to therapeutics. This review introduces current progress in different breast cancer experimental animal models and analyzes their characteristics, advantages, disadvantages, and potential applications. Finally, we propose future research directions for breast cancer animal models.

Unraveling the complexity of polycystic ovary syndrome with animal models

Polycystic ovary syndrome (PCOS) is a highly familial and heritable endocrine disorder. Over half of the daughters born to women with PCOS may eventually develop their own PCOS-related symptoms. Progress in the treatment of PCOS is currently hindered by the complexity of its clinical manifestations and incomplete knowledge of its etiopathogenesis. Various animal models, including experimentally induced, naturally occurring, and spontaneously arising ones, have been established to emulate a wide range of phenotypical and pathological traits of human PCOS. These studies have led to a paradigm shift in understanding the genetic, developmental, and evolutionary origins of this disorder. Furthermore, emerging evidence suggests that animal models are useful in evaluating state-of-the-art drugs and treatments for PCOS. This review aims to provide a comprehensive summary of recent studies of PCOS in animal models, highlighting the power of these disease models in understanding the biology of PCOS and aiding high-throughput approaches.

Animal models of mpox virus infection and disease

Mpox(monkeypox)virus(MPXV),which causes a mild smallpox-like disease,has been endemic in Africa for several decades,with sporadic cases occurring in other parts of the world.However,the most recent outbreak of mpox mainly among men that have sex with men has affected several continents,posing serious global public health concerns.The infections exhibit a wide spectrum of clinical presentation,ranging from asymptomatic infection to mild,severe disease,especially in immunocompromised individuals,young children,and pregnant women.Some therapeutics and vaccines developed for smallpox have partial protective and therapeutic effects against MPXV historic isolates in animal models.However,the continued evolution of MPXV has produced multi-ple lineages,leading to significant gaps in the knowledge of their pathogenesis that constrain the development of targeted antiviral therapies and vaccines.MPXV infections in various animal models have provided a central plat-form for identification and comparison of diseased pathogenesis between the contemporary and historic isolates.In this review,we discuss the susceptibility of various animals to MPXV,and describe the key pathologic features of rodent,rabbit and nonhuman primate models.We also provide application examples of animal models in elu-cidating viral pathogenesis and evaluating effectiveness of vaccine and antiviral drugs.These animal models are essential to understand the biology of MPXV contemporary isolates and to rapidly test potential countermeasures.Finally,we list some remaining scientific questions of MPXV that can be resolved by animal models.

“Blind men and an elephant”:The need for animals in research,drug safety studies,and understanding civilizational diseases

Animal-based research and drug safety studies are essential to understanding the mysteries of nature and the long-term survival of humans.Due to the rapid increase in the global human population,conflict-and economically driven human migration,tourism-related activities,densely populated metropolitan areas,and local policies,humans will be affected by a multitude of novel disease-causing microorganisms and civilizational diseases.Despite disparities among countries,recent and planned changes in regulations concerning animal research and drug safety studies could have detrimental effects on both the animal research community and nations lacking sufficient social support systems.Based on existing scientific literature,I argue that we need animal research encompassing aspects such as animal development,behavior,drug safety studies,and for the understanding of future civilizational diseases.Depending on the nature of the research questions and local challenges,a suitable animal model organism should be made mandatory.

长爪沙鼠不同感音神经性耳聋模型的建立及比较

目的利用不同的耳毒性药物建立长爪沙鼠感音神经性耳聋模型,并对3种模型进行比较分析,为感音神经性耳聋的研究提供精准的动物模型。方法选择长爪沙鼠,建立硫酸卡那霉素和呋塞米联用(KM+Fur)、新霉素(Neo)及哇巴因(Oua)3种耳毒性药物的感音神经性耳聋模型,通过听性脑干反应(ABR)和耳蜗组织形态学检测,比较分析不同耳毒性药物的损伤特点。结果KM+Fur造模后,与对照组(14.00±1.80)相比,该组(71.00±5.26)长爪沙鼠的听力阈值显著上升,耳蜗HCs大量损伤,而SGNs无明显损伤;Neo造模后,与对照组相比,40 mmol·L^(-1) Neo仅影响沙鼠高频32 kHz时听力阈值(60.00±8.66),无明显的组织学改变;而100 mmol·L^(-1) Neo组的沙鼠各频率听力阈值均显著上升,且耳蜗HCs及SGNs均严重受损;Oua造模后,1 mmol·L^(-1) Oua和10 mmol·L^(-1) Oua均可引起沙鼠各频率听力阈值显著上升,但损伤范围不同,10 mmol·L^(-1) Oua使HCs和SGNs均严重受损,而1 mmol·L^(-1) Oua仅造成耳蜗SGNs损伤。结论利用KM+Fur可建立长爪沙鼠HCs特异性受损的感音神经性耳聋模型;40 mmol·L^(-1) Neo可建立高频区听功能损伤的感音神经性耳聋模型;利用100 mmol·L^(-1) Neo和10 mmol·L^(-1) Oua可以建立长爪沙鼠HCs和SGNs均受损的感音神经性耳聋模型;利用1 mmol·L^(-1) Oua可以建立长爪沙鼠耳蜗SGNs特异性受损的耳聋模型。

创伤性脑损伤及其治疗药物

创伤性脑损伤(traumatic brain injury,TBI)是一种威胁人类生命安全的常见损伤。由于其损伤机制复杂,目前外科手术是临床首选治疗手段,但针对手术后继发性TBI的预防与治疗尚没有有效治疗药物。研究TBI损伤机制、寻找有效治疗药物以减轻患者痛苦、提高生活质量,成为目前的研究热点。本综述概括了近几年有关TBI治疗的最新进展,包括TBI损伤机制、TBI动物模型建立和评价指标、治疗药物及其新型递送系统,其中新型药物递送系统概括了聚合物纳米粒、水凝胶、树枝状聚合物、脂质体、胶束和细胞外囊泡作为新型药物载体在TBI治疗中的应用,希望为安全、有效地治疗TBI提供新思路。

听源性癫痫动物模型研究进展

听源性癫痫(audiogenic seizures,AGS)是由于强声刺激引起的癫痫,发作时伴全身性肌肉痉挛,其动物模型在研究癫痫发生机制、寻找致病基因及调控通道、筛选新的抗癫痫药物(antiepileptic drugs,AEDs)等方面具有重要意义。本文从发病特点、发病机制及致病基因等方面总结了目前常见AGS动物模型研究进展,以期为AEDs研发提供新的研究方向和靶点。

药源性心脏毒性模型的构建与评价进展

目的了解药源性心脏毒性动物模型的建立与应用,为药源性心脏毒性的防治提供研究基础。方法采用文献研究,以“心脏毒性”和“cardiotoxicity”等为主题词,在中国知网和Web of science core collection数据库选取2015年1月1日至2024年4月4日应用药源性心脏毒性模型的相关文献,按照纳入标准筛选出应用药源性心脏毒性动物模型的实验研究文献,并使用分析软件Citespace 6.3R1(64-bit)Basic结合Excel对纳入文献进行可视化呈现。结果共纳入731篇文献。应用于药源性心脏毒性研究的模式动物多选用大鼠、小鼠、斑马鱼,造模剂以阿霉素、乌头碱、布比卡因为主,毒性机制涉及氧化应激、细胞凋亡等。大多采用一般指标、组织病理指标、心脏功能检测指标等多类别指标变化进行综合评价。其应用也较为集中,评价药源性心脏毒性模型的标准存在较大差异。结论目前药源性心脏毒性模型的研究仍具有一定的发展前景,为系统开展中医药防治药源性心脏毒性提供依据。

关于ILAE/AES联合报告“重新审视耐药性癫痫概念”的解读

尽管新型抗癫痫药物(ASMs)不断涌现,目前已经发展到第三代,但仍有1/3癫痫患者可发展为耐药性癫痫(DRE)。早在2010年,国际抗癫痫联盟(ILAE)就提出了DRE概念并沿用至今,及早诊断DRE,有助于对ASMs无反应的个体进行术前评估,并从癫痫外科手术中受益。由于DRE的发病率仍然很高以及概念一直没有更新,故在2023年8月ILAE/美国癫痫协会(AES)联合工作组从协调临床前和临床研究角度出发,在整个生命周期和跨物种基础上讨论了DRE表现和机制的异质性、复杂性及动态变化。联合工作组建议有必要重新审视DRE的当前定义,以更好地服务DRE临床管理以及指引DRE未来研究方向,为患者筛选更有效、更精准的个体化治疗,以减少DRE发病率,提高患者生活质量。本文旨在就ILAE/AES此份报告做一简要介绍和解读。

骨髓增生异常综合征在斑马鱼中的研究进展

骨髓增生异常综合征(myelodysplastic syndrome,MDS)是一种常见的血液疾病,其发病率呈现逐年上升的趋势。斑马鱼作为一种生物医学研究的模式生物,广泛应用于各类疾病的研究中。本文关注了近年来血液疾病在斑马鱼中的研究,MDS在小鼠、大鼠和斑马鱼中的研究及动物模型的应用,揭示了斑马鱼模型在其中发挥的重要作用。

Systematic review of robust experimental models of rheumatoid arthritis for basic research

Rheumatoid arthritis(RA)is a common autoimmune disease characterized by progressive joint inflammation and destruction,deformity,loss of mobility,and permanent disability.Although the cellular and molecular mechanisms involved in RA are understood in detail,no drugs or therapies can completely cure RA.Many long-term efforts have been directed towards a better understanding of RA pathogenesis and the development of new classes of therapeutics.Thus,the ongoing elucidation of pathogenic events underlying RA mostly relies on studies of animal models.Herein,we comprehensively review and discuss the characteristics,challenges,and unresolved of issues of various experimental models of RA to provide a basis and reference for the rational selection of experimental RA models for basic investigations into traditional Chinese medicine(TCM).

射血分数保留型心力衰竭的病理生理及治疗药物进展

射血分数保留型心力衰竭在心力衰竭中占40%~71%,是一种涉及心、肾、肺、血管系统和脂肪组织等的多系统疾病,严重影响患者的生活水平。近年来,随着医疗研究水平不断提升,射血分数保留型心力衰竭临床治疗取得一定的效果,但患者仍然存在预后不良情况,复发率升高而生活质量下降。文章通过对射血分数保留型心力衰竭近年国内外相关研究报道进行综述,发现其病理生理机制主要与高血压、冠脉疾病和冠脉微血管功能障碍、左心功能不全、右心室功能障碍和肺动脉疾病、激素系统异常、肥胖、系统性炎症和代谢异常相关,通常使用利尿剂、RAAS抑制剂、SGLT2is、MRA和他汀类药物进行治疗,不同分型的动物模型的构建也为射血分数保留型心力衰竭临床诊治提供一些有价值参考。

人类肠道病毒的研究进展

自1908年脊髓灰质炎病毒被鉴定以来,已发现超百种肠道病毒致病血清型,可引起手足口病、新生儿败血症样疾病、无菌性脑炎、急性弛缓性脊髓炎、呼吸系统疾病、急性出血性结膜炎等多种疾病。近年来,诸如EV-A71和EVD68等肠道病毒趋于全球化周期性流行,已成为公共卫生领域不可忽视的重要挑战之一。然而,当前针对肠道病毒的防控手段仍然非常有限,迫切需要深入探究肠道病毒致病的分子机制,为开发高效、安全、广谱的抗肠道病毒药物提供新靶点与新思路。本文通过对肠道病毒的分类、流行病学、结构、生命周期、病毒蛋白与宿主因子相互作用、并发症致病机制与临床治疗以及动物感染模型的确立与应用等方面进行系统的综述,旨在为肠道病毒防治提供理论参考依据,为肠道病毒的药物研发与疫苗储备库建设提供新的思路。

药物诱导肺动脉高压动物模型的影像学评估研究进展

肺动脉高压(PAH)是一种具有极高致死率的慢性疾病,其主要特征为肺血管进行性重构。在深入理解PAH发病机制和探索新治疗策略的过程中,药物诱导的PAH动物模型发挥了至关重要的作用。现就野百合碱(MCT)和血管内皮生长因子受体抑制剂(SU5416)诱导的PAH模型及影像学评估展开综述,详细介绍建模方法、实验动物的选择,以及超声、显微CT(Mircro CT)、心脏磁共振(CMR)在PAH模型建立后评估中的应用。

环磷酰胺诱导的小鼠免疫低下模型的方法学考察及金樱子提取物联合益生菌调节免疫功能的研究

目的:建立更符合人体免疫低下状态的小鼠模型,并基于此模型考察金樱子、益生菌以及二者联合用药对免疫功能的调节作用。方法:采用不同给药剂量、时间和实验终点的环磷酰胺建立小鼠免疫低下模型,并与氢化可的松及环孢素A诱导的免疫低下模型对比,确立了25 mg/kg环磷酰胺隔日共注射7次,无恢复期的免疫低下小鼠模型;流式细胞术检测小鼠脾脏淋巴细胞(CD4^(+)T细胞、CD8^(+)T细胞、CD19^(+)B细胞)比例变化;qRT-PCR检测小鼠脾脏炎症因子(IL-1β、IL-6)mRNA表达。结果:80 mg/kg环磷酰胺连续注射3 d后,胸腺萎缩,脾脏肿大,脾脏中CD4^(+)T细胞、CD8^(+)T细胞、CD19^(+)B细胞比例下降,IL-1β及IL-6 mRNA表达上调;25 mg/kg环磷酰胺隔日注射共7次后,胸腺和脾脏萎缩,脾脏中CD4^(+)T及CD8^(+)T细胞比例呈升高趋势,IL-1β及IL-6 mRNA表达上调;环磷酰胺造模后恢复1周或2周,小鼠免疫器官重量和指数、脾脏淋巴细胞比例、脾脏炎症细胞因子mRNA表达均显著恢复;金樱子联合益生菌可显著恢复环磷酰胺导致的CD4^(+)T细胞上调以及炎症因子IL-1β上调。结论:本研究建立了25 mg/kg环磷酰胺隔日注射共7次,无恢复期的免疫低下小鼠模型,并基于此模型发现金樱子联合益生菌具有一定的正向免疫调节作用。

腹泻动物模型及治疗药物研究进展

腹泻是临床常见并且多发的疾病,引发腹泻的因素也比较多,目前有关腹泻动物模型的研究方法也比较多,但在临床上治疗腹泻的药物种类有限,现有的一部分药物也只适用于单一因素的腹泻。因此构建及选择合适的腹泻动物模型不仅是深入研究腹泻发病机制的重要基础,也是临床筛选和评价全面防治腹泻药物的有效手段。本文综述功能性、细菌性、病毒性、症状性腹泻动物模型的建立和评价以及治疗药物研究进展,以期为腹泻有关的动物实验研究和药物防治提供参考依据。

自发性脑出血动物模型选择及临床前药物试验指南(2024年版)

自发性脑出血(spontaneous intracerebral hemorrhage,sICH)是最常见和致死性最高的卒中类型,其特征是脑实质的自发性出血,目前尚无有效的防治方法。现有的sICH动物模型可以概括为三大类:(1)诱导性脑出血模型,主要有自体血注入、胶原酶注射、微气球充盈、高血糖诱导的sICH血肿扩大模型;(2)自发性高血压脑出血模型,主要有易卒中性自发性高血压大鼠和易卒中性肾血管性高血压大鼠模型;(3)基因修饰模型,主要有高血压脑出血转基因模型、脑淀粉样血管病转基因模型、脑动静脉畸形病变相关基因修饰模型、脑海绵状血管畸形相关基因修饰模型及胶原蛋白相关基因修饰模型。这些模型不仅帮助我们了解sICH的发病机制、探索预防或治疗的方法,也可用于临床前药物试验,促进sICH新药研发工作。本指南系统总结了sICH的发病机制,详细介绍了不同种属建模动物的优劣性、不同sICH动物模型的建模原理和方法、建模技术细节、模拟的病理生理机制及其临床相关性以及sICH动物模型神经行为评价技术,并比较了各种sICH模型的优缺点及其适用的研究范围,最后重点概括了sICH相关的临床前药物试验设计要点。

卡培他滨致小鼠手足综合征模型的建立及评价

目的手足综合征是卡培他滨的剂量限制性毒性反应。目前手足综合征模型的建立并没有统一的金标准,本实验给予ICR小鼠灌胃卡培他滨,诱导手足综合征发生,为手足综合征模型的建立提供借签。方法42只雄性ICR小鼠随机分为对照组(6只)和实验组(36只),实验组持续2周灌胃给予卡培他滨(275 mg/kg,2次/d),对照组给予溶剂0.5%CMCNa(4 ml/kg,2次/d),取小鼠足部皮肤样本进行H&E染色,观察足跖部特征性外观以及形态改变,评估手足综合征的动物模型是否成功构建;实验结束后处死小鼠,收集血浆,定量其中卡培他滨及其代谢产物浓度改变。结果6只对照组小鼠均未出现手足综合征症状;实验组19只小鼠足部皮肤出现红斑、肿胀等症状,H&E染色可见部分足底皮肤角表皮层增厚,部分角质脱失破损,判断为发生手足综合征。发生与未发生手足综合征小鼠血浆中卡培他滨及其代谢产物浓度未见明显差异。结论卡培他滨致小鼠手足综合征的模型构建成功;卡培他滨及其代谢产物体内暴露水平差异可能不是手足综合征发生的原因。