Knee osteoarthritis:A review of animal models and intervention of traditional Chinese medicine

Background:Knee osteoarthritis(KOA)characterized by degeneration of knee cartilage and subsequent bone hyperplasia is a prevalent joint condition primarily affecting aging adults.The pathophysiology of KOA remains poorly understood,as it involves complex mechanisms that result in the same outcome.Consequently,researchers are interested in studying KOA and require appropriate animal models for basic research.Chinese herbal compounds,which consist of multiple herbs with diverse pharmacological properties,possess characteristics such as multicomponent,multipathway,and multitarget effects.The potential benefits in the treatment of KOA continue to attract attention.Purpose:This study aims to provide a comprehensive overview of the advantages,limitations,and specific considerations in selecting different species and methods for KOA animal models.This will help researchers make informed decisions when choosing an animal model.Methods:Online academic databases(e.g.,PubMed,Google Scholar,Web of Science,and CNKI)were searched using the search terms“knee osteoarthritis,”“animal models,”“traditional Chinese medicine,”and their combinations,primarily including KOA studies published from 2010 to 2023.Results:Based on literature retrieval,this review provides a comprehensive overview of the methods of establishing KOA animal models;introduces the current status of advantages and disadvantages of various animal models,including mice,rats,rabbits,dogs,and sheep/goats;and presents the current status of methods used to establish KOA animal models.Conclusion:This study provides a review of the animal models used in recent KOA research,discusses the common modeling methods,and emphasizes the role of traditional Chinese medicine compounds in the treatment of KOA.

Effect of traditional Chinese medicine on anthracycline-induced cardiotoxicity in animal models:A systematic review and metaanalysis

Objective:To evaluate the effect of traditional Chinese medicine(TCM)on anthracycline-induced cardiotoxicity(AIC)in animal models.Methods:Separate systematic searches for preclinical studies were performed in the PubMed,EMBASE,Web of Science,Chinese National Knowledge Infrastructure,Chinese Biomedical Database,Chinese Scientific Journal Database,and Wanfang Data from inception to August 2019.The primary outcomes were echocardiography,serum assays for myocardial enzymograms,histological assessments,and electrocardiograms.The secondary outcomes mainly included body weight and safety evaluations.The protocol is registered on PROSPERO(CRD42019145819).RevMan(V.5.3)was used for meta-analysis.Results:We identified 10 studies from 9 international scientific publications describing the efficacy of TCM on AIC animal models.All the included studies reported that,compared with animal model without any intervention,TCM significantly improved ventricular function,cardiac biomarkers,electrocardiograph results,and cardiac fibrosis.Improved survival rates and body mass indices were also observed with TCM.We further pooled the available data from four studies(63 animals)for the meta-analysis and the results showed that,compared with models without any intervention,TCM significantly increased the ejection fraction by 14.13%(95%CI,9.96e18.29)and fraction shortening by 8.66%(95%CI,6.05 e11.26).Creatine kinase-MB(SMD=2.49,95%CI:-3.12 to-1.85)and lactate dehydrogenase(SMD=-2.78,95%CI:-3.45 to-2.12)were also significantly decreased by TCM.Conclusions:TCM is effective in improving AIC in animal models and has tremendous potential to be translated to treat AIC in clinical practice.Additionally,the systematic review and meta-analysis of animal experiments may be valuable in enhancing and guiding animal experiments and promoting the transformation of the results.

Research Survey of Animal Model of Hepatic Fibro-sis Integrated with Western Medicine Diseases and Traditional Chinese Medicine^TCM~)Syndrome

Although the animal models of hepatic fibrosis developed by former researchers have pathological changes of hepatic fibrosis, they do not include charac- teristics of important TCM syndromes such as stagnation of qi, deficiency of qi, liver depression, phlegm-dampness and blood stasis because of single-factor model- ing. Animal models of hepatic fibrosis and animal models integrated disease and syndrome were reviewed, and several new types of integrated disease and syndrome animal models constructed by multiple-factor modeling method were evaluated, under the guidance of etiological theory of TCM. This kind of hepatic fibrosis model animals has dual characteristics of disease and syndrome. It is consistent with pathological characteristics of hepatic fibrosis in western medicine when replicating the basic characteristics accorded with TCM syndrome. Thus, the pathogenesis and pathogenic process of clinical disease and syndrome formation is simulated more ac- curately, providing a new platform and pathway for studying hepatic fibrosis disease with integrated traditional Chinese and western medicine.

Update on establishment of TCM animal model of myocardial ischemia and Chinese medicine treatment

The prevention and treatment of myocardial ischemia is a hot and difficult point in clinical research and animal experimental research in the cardiovascular field.The combined disease and syndrome animal model with the disease characteristics of Western medicine and guided by the theory of Chinese medicineto replicate the"syndrome"of Chinese medicine on the model animals by using experimental methods is an effective tool for the research of Chinese medicine.This article summarized the methoding methods and evaluation index of the animal model combined disease of coronary heart disease myocardial ischemia with cold blood stasis,phlegm and blood stasis,qi deficiency and blood stasis syndrome,kidney deficiency and blood stasis,and concluded the treatment of Traditional Chinese medicine.At the same time,it analyzed the main deficiencies of myocardial ischemia syndrome combined with animal models to provide reference for the establishment and research of related animal models.

Chinese medicine in the treatment of autoimmune hepatitis:Progress and future opportunities

Autoimmune hepatitis(AIH)is a chronic inflammatory liver disease occurring in indi-viduals of all ages with a higher incidence in females and characterized by hypergam-maglobulinemia,elevated serum autoantibodies and histological features of interface hepatitis.AIH pathogenesis remains obscure and still needs in-depth study,which is likely associated with genetic susceptibility and the loss of immune homeostasis.Steroids alone and in combination with other immunosuppressant agents are the pri-mary choices of AIH treatment in the clinic,whereas,in some cases,severe adverse effects and disease relapse may occur.Chinese medicine used for the treatment of AIH has proven its merits over many years and is well tolerated.To better under-stand the pathogenesis of AIH and to evaluate the efficacy of novel therapies,several animal models have been generated to recapitulate the immune microenvironment of patients with AIH.In the current review,we summarize recent advances in the study of animal models for AIH and their application in pharmacological research of Chinese medicine-based therapies and also discuss current limitations.This review aims to provide novel insights into the discovery of Chinese medicine-originated therapies for AIH using cutting-edge animal models.

Application status and research progress of animal models of knee osteoarthritis

Appropriate animal model is the basis for the smooth development of scientific research,and also the guarantee of the experimental results.As a common clinical disease,the pathogenesis of KOA and the mechanism of action of various treatment methods need to be explored and verified by a large number of animal experiments.The selection and establishment of animal model is an important link,The selection of modeling methods in western medicine and the establishment of the model of combination of disease and syndrome in traditional Chinese medicine are the key points and difficulties.In this paper,the selection of KOA animal models was reviewed through literature retrieval,and the status quo of model establishment methods was summarized from the perspectives of western medicine and TCM.The main animal species include mice,chicken,rabbit,dog,sheep,horse,pig,monkey,emu and so on.The establishment methods of western medicine and TCM models are different.Western medicine models can be divided into spontaneous model induction model and transgenic model according to different establishment methods while TCM models are mainly established according to their syndromes.

2023年中医诊断学研究进展

2023年,中医诊法理论研究主要集中在望诊和脉诊领域,致力于将诊法理论与临床病证紧密结合,并扩展到舌诊、面诊、鼻诊和手诊等领域,结合现代影像学技术,提高了诊断的灵活性和准确性。多维辨证体系构建为现代医学所需,结合现代技术在心血管病、咳嗽、疫病等方面得到应用,开辟了中西医结合新途径。证候辨证研究通过横向数据揭示证候分布的规律性,旨在规范研究,客观反映病因、病机及病情发展趋势。动物模型成为验证中医理论和探索新治疗方法的关键,在线粒体功能、能量代谢、免疫调节和炎症反应等方面,揭示了证候的生物学基础,分析及揭示了代谢物、基因表达、细胞因子等标志物及肠道菌群变化与证候形成的相关关系。传统中医诊断技术与大数据分析、机器学习和传感器技术结合,在舌诊、面诊、脉诊等领域取得进展,显著提高了诊断方法的精准度和客观性,应用高通量影像组学参数分析、注意力机制模型和电子鼻技术,提升了中医诊断的标准化和科学性,也为远程医疗和个性化诊疗创造了新的可能性。

脾虚证动物模型研究述评

中医界运用现代科学方法进行相关研究已有多年历史,在病证动物模型上颇有收获。本文对脾虚证动物模型发展历程进行回顾,对动物选择、造模方法、评价指标、消化系统病证结合模型进行总结和评论。模型动物多选用以大鼠为代表的小型啮齿类。目前,多基于病因病机造模,而较少使用化学药物与物理因素造模,复合因素造模法最常见。评价指标则分为中医证型指标、与“脾”功能和特性有关量化指标,以及方剂反证。功能性腹泻/消化不良为代表的脾虚证病证结合模型是目前研究的重心。脾虚证动物模型研究成绩斐然的同时仍存在许多不足,如缺乏脾虚证模型行业标准和共识,评价指标缺乏系统性和整体性,脾虚理论的现代阐释缺乏统一,学界亟需解决上述问题以促进发展。

基于中西医临床病证特点的免疫性血小板减少动物模型分析

原发免疫性血小板减少(ITP)是一种出血性疾病,发病机制目前尚不明确,为了进一步探究ITP发病机制和临床新药的研究,故通过查阅大量国内外关于免疫性血小板减少模型的相关文献,参照中西医病因病机和临床疾病诊断标准,总结分析ITP相关动物模型特点和与临床吻合度。发现应用最为广泛的是抗血小板血清诱导法,其临床吻合度与病证结合脾不统血、气不摄血模型吻合度均较高,模型造模方式简单,可重复性强。但大多数模型将西医作为评价指标,模型无法完全模拟ITP完整发病过程和状态,缺少中医证候描述,在模型发展仍需进一步完善。

中药调控氧化应激治疗男性不育症实验研究进展

氧化应激(OS)是指机体遭受各种有害刺激时产生过多的活性氧自由基而无法及时清除,导致氧化系统和抗氧化系统平衡失调,引起组织或细胞功能紊乱和损伤的一种状态。OS与男性不育症(MI)关系密切,OS通过影响精子发生,损伤精子膜、脱氧核糖核酸(DNA)、线粒体,降低精子运动能力,加速细胞凋等途径使精子质量下降,导致MI。研究发现,单味中药的有效成分多糖类化合物(黄芪多糖、党参多糖、枸杞多糖、黄精多糖、山茱萸多糖、当归多糖、女贞子多糖、石斛多糖),黄酮类化合物(菟丝子总黄酮、槲皮素、紫云英苷、羊藿苷、金丝桃苷),皂苷类化合物(人参皂苷、蒺藜皂苷、薯蓣皂苷元),苯丙素类化合物(五味子甲素、姜黄素、白藜芦醇),环烯醚萜苷类化合物(桃叶珊瑚苷),氮苷类化合物(红景天苷),低聚糖类化合物(巴戟甲素),苯乙醇苷类化合物(肉苁蓉苯乙醇苷)多肽类化合物(牡蛎肽)具有抗氧化作用,可提升雄性动物MI模型的生殖功能。

基于文献分析研究前列腺增生大鼠模型特点

目的:研究对大鼠前列腺增生造模特点与指标特征,为提高实验造模效率和科学评价药物防治的价值提供参考及依据。方法:于国家知识基础设施数据库(CNKI)收集2001年1月至2023年2月研究大鼠前列腺增生动物模型文献共计228篇,录入动物模型造模动物类型、造模药、阳性对照药、受试药、药物给药时间、给药剂量、给药方式及部位、评价指标和测试指标等信息,进行统计与分析。结果:推荐选取SD雄性大鼠,造模方案为切除大鼠双侧睾丸,连续30 d腹腔注射丙酸睾酮3~5 mg/kg,1次/d;常见指标:组织生化指标、血清生化指标、前列腺组织病理学指标等。治疗药物以非那雄胺为主,常用中药复方为仙甲汤、隆畅胶囊以及加味桂枝茯苓颗粒等,给药周期均为30 d左右。结论:通过分析讨论可得出,高效准确的造模方式对前列腺增生动物模型成模及治疗具有一定的参考意义。

基于中西医临床病症特点的肠易激综合征动物模型评价

肠易激综合征(IBS)是一种以慢性或者反复性腹痛同时伴随着排便异常或排便习惯变化为特点的功能性胃肠道疾病。目前IBS动物模型吻合度较高的为多因素联合的病症结合模型,但此类模型多为中药灌胃合并某证型,多因素造模方法在IBS复杂的病因病机方面也存在一定的局限性。而更完善的动物模型可以有助于临床研究和筛选治疗药物。构建更加符合中西医临床病症特点的动物模型尤为重要。基于IBS的中西医临床病症特点,对现有的IBS模型进行归纳分析,评价动物模型和临床的吻合度,分析其优缺点。完善动物模型评价标准,结合中医优势联系各建模方法的相互作用,结合环境、遗传、生活方式等因素,是未来IBS动物模型的发展方向。

缺血性卒中后抑郁动物模型中医病证研究进展

缺血性卒中后抑郁(post-ischemic stroke depression)是脑血管病变常见的并发症。该文对国内近年来缺血性卒中后抑郁造模方法及其模型评估、缺血性卒中后抑郁中医病证结合动物模型造模方法的研究进展进行综述,以期为拓展中医疗法的临床应用及开展其疗效机制的研究提供基础。缺血性卒中后抑郁模型多采用脑卒中模型合并郁证的方法造模,主要有线栓法结扎颈内动脉联合慢性不可预见性温和应激(chronic unpredictable mild stress,CUMS)及孤养法,线栓法结扎左颈内动脉、右颈外动脉和左右椎动脉联合孤养及束缚应激法,以及线栓法结扎一侧颈总动脉联合可预见刺激及孤养法。缺血性卒中后抑郁中医病证结合动物模型涉及肝气郁滞证、气虚血瘀证、痰蒙神窍证、肾虚证的缺血性卒中后抑郁动物模型的制备。目前建立的缺血性卒中后抑郁中医病证结合动物模型,虽具备西医病理表现和中医证候的病症特征,但是否能反映临床患者的病证结合本质,仍有待研究。

基于病证结合探讨常见脾胃病动物模型的构建与评价

动物实验对促进新药研发和明确药理机制具有重要意义,随着中医药现代化发展,病证结合动物实验被越来越多的学者广泛应用,动物模型的构建与评价体系也在逐步完善。脾胃系疾病发病率高,不易治愈,中医药治疗脾胃病具有独特优势,为深入研究中医中药治疗脾胃病的分子机制及药效效果,制备其相关的病证结合动物模型意义重大。单纯西医疾病模型具有一定局限性,病证结合动物模型符合中医辨证论治原则,对脾胃病的病机阐明和新药研发尤为重要。因此,笔者通过对常见脾胃病病证结合动物模型各证候的构建方法和评价系统进行归纳总结,阐述脾胃病病证结合动物模型的发展概况和建立特点,以期解决动物实验模型病证评价指标的关键问题,完善病证造模与测量标准,为研究人员提供参考依据,推动中医药治疗脾胃病进一步发展。

Chrysophanol attenuates lead exposure-induced injury to hippocampal neurons in neonatal mice

Previous studies have shown that chrysophanol protects against learning and memory impairments in lead-exposed adult mice. In the present study, we investigated whether chrysophanol can alleviate learning and memory dysfunction and hippocampal neuronal injury in lead-exposed neonatal mice. At the end of lactation, chrysophanol（0.1, 1.0, 10.0 mg/kg） was administered to the neonatal mice by intraperitoneal injection for 15 days. Chrysophanol significantly alleviated injury to hippocampal neurons and improved learning and memory abilities in the lead-poisoned neonatal mice. Chrysophanol also significantly decreased lead content in blood, brain, heart, spleen, liver and kidney in the lead-exposed neonatal mice. The levels of malondialdehyde in the brain, liver and kidney were significantly reduced, and superoxide dismutase and glutathione peroxidase activities were significantly increased after chrysophanol treatment. Collectively, these findings indicate that chrysophanol can significantly reduce damage to hippocampal neurons in lead-exposed neonatal mice.

Use of Qishen granule for the treatment of heart failure: A systematic review and meta-analysis of animal studies

Objective:To evaluate the effect of Qishen granule(QSG)on heart failure(HF)and the potential mechanisms involved in animal models.Methods:Studies of QSG in animals with HF were identified by searches of eight databases up to August 1,2019.Two authors independently reviewed each study and the Collaborative Approach to Metaanalysis and Review of Animal Data from Experimental Studies 10-item checklist was used for quality assessment.The primary outcomes were indicators of left ventricular ejection fraction and/or left ventricular fractional shortening.The secondary outcome measures were ventricular structure,hemodynamics,myocardial injury-related indicators,and the mechanisms whereby QSG ameliorates HF.A metaanalysis was performed and all the data were analyzed using RevMan 5.3 software.Results:Thirteen studies containing a total of 240 animals met the criteria for the meta-analysis.The quality score of the studies ranged from three to six points.The meta-analysis showed a significant effect of QSG to improve cardiac function,inhibit ventricular remodeling,improve circulation,and attenuate myocardial injury.The possible mechanisms was identified to be suppression of the renin-angiotensinaldosterone system,which has anti-fibrotic,anti-apoptotic,anti-inflammatory,and anti-oxidative effects in the myocardium,the prevention of calcium overload,and the promotion of myocardial energy metabolism.Conclusion:Our review shows that QSG has a cardioprotective effect in animal models of CHF.However,due to the relatively poor quality of the included studies and the differences between humans and animal models,the results should be interpreted with caution.

人冠状病毒229E湿热疫毒袭肺病证结合小鼠模型的建立及评价

目的在采用外部湿热因素造成中医湿毒袭肺小鼠模型的基础上,同时采用人冠状病毒229E(HCoV-229E)感染小鼠造成肺炎模型,建立湿热疫毒袭肺病症结合小鼠模型。方法对湿热感染不同天数的小鼠中医证候表征、肺指数和肺部病毒载量、肺部病理结构与影像学、小鼠血清胃泌素(Gas)、下丘脑前列腺素E2(PGE2)、环磷酸腺苷(c AMP)及肌糖原评价湿毒疫动物模型。结果人冠状病毒肺炎湿热疫毒袭肺证小鼠病证结合模型小鼠饮食量下降和饮水量增加,毛发枯燥发黄,行动迟缓爱扎堆,大便便溏。肺指数增加(P<0.01),肺部病毒核酸呈阳性表达,肺组织可见病理结构变化及斑点状阴影。小鼠体内肌糖原含量、血清胃泌素含量、下丘脑c AMP、PGE2的含量在感染后均有显著升高(P<0.05)。结论本研究建立的HCoV-229E湿热疫毒袭肺证病证结合小鼠模型与临床疾病表征具有一致性,可为诊断及治疗具有该证候的病毒性肺炎与开发相关药物研究提供一种可靠的评价动物模型。

基于中西医临床病证特点的系统性红斑狼疮动物模型研究评述

基于系统性红斑狼疮(SLE)的中西医临床病证特点,参考国内外SLE动物模型研究文献,依据临床诊断标准,对现有模型的临床符合度进行评价,经对比分析发现,自发小鼠模型中的MRL/lpr小鼠模型与诱导模型中的姥鲛烷诱导模型中西医临床病证吻合度最高。但目前SLE动物模型多按照西医病因特点建模,缺乏中医病证结合模型,中医符合度低,因此在现有研究基础上增加中医干扰因素,彰显中医辨证优势,加强SLE中医辨证相关研究是今后努力的方向。

中药药效研究常用模型总结与思考

[目的]通过梳理中医药疾病动物模型的研究和发展现状,对中医药常用动物模型的特点、优势以及存在的问题进行介绍,为建立适合中医药特点的动物模型提供参考。[方法]从中药药效研究常用动物模型的特点及存在的问题、目前中药药效学研究用模型的困境、理想的研究模型应具备的特点、现有动物模型特点及其在中医药研究领域的应用几个方面进行梳理与思考。[结果]当前中药药效学研究常用模型的造模方法主要有中医病因学造模法、现代病因病理造模法和病证结合造模法,常用模型有整体动物模型、离体器官组织动物模型、细胞株动物模型、模式动物模型、类器官模型和基因修饰动物模型,不同分类模型应用在中医药领域各有其特点、优势和不足。其中病证结合动物模型在中药药效研究中具有诸多优势,成为中药药效研究的发展趋势。[结论]病证结合动物模型将西医疾病与中医证候有机结合,更好地体现中医整体化思维,更符合中医整体观和辨证观,是较为理想的中药药效研究动物模型。