基于中西医临床病证特点的重症肌无力动物模型分析

doi:10.12300/j.issn.1674-5817.2024.139

实验动物与比较医学 ›› 2025, Vol. 45 ›› Issue (2): 176-186.DOI: 10.12300/j.issn.1674-5817.2024.139

基于中西医临床病证特点的重症肌无力动物模型分析

陈钰涵¹, 陈瑾玲¹, 李欣²^,³, 区燕华²^,³, 王斯¹, 陈镜伊¹, 王兴易¹, 袁嘉丽¹, 段媛媛²^,³, 羊忠山¹, 牛海涛¹^,²^,³()()

^1.云南中医药大学云南省中西医结合慢病防治重点实验室, 昆明 650500
^2.病毒致病及防控教育部重点实验室(暨南大学), 暨南大学基础医学与公共卫生学院, 广州 510632
^3.广州市无菌动物与微生态转化重点实验, 暨南大学实验动物管理中心, 广州 510632

收稿日期:2024-09-23 修回日期:2024-12-31 出版日期:2025-04-25 发布日期:2025-04-25
通讯作者: 牛海涛（1970—），男，教授，博士生导师，研究方向：肠道微生态与机体免疫系统互作研究。E-mail： htniu@jnu.edu.cn。ORCID： 0000-0003-2210-2051
作者简介:陈钰涵（1999—），女，硕士研究生，研究方向：肠道微生态与机体免疫系统互作研究以及抗肿瘤免疫微生态研究。E-mail： chenyu22900442@163.com
基金资助:
科技部重点研发计划“重要消化道肿瘤、免疫疾病小鼠模型的研发与功能机制研究”(2022YFF0710701);科技部重点研发计划“重要神经退行性疾病和免疫疾病大鼠模型的研发与功能机制研究”(2022YFF0710702);广州市重点研发计划项目“小檗碱调节肠道微生物影响心血管病发病关系研究”(202206010157);广州市校联合项目“广州市无菌动物与微生态转化重点实验室项目”(202201020381);暨南大学医学联合基金“食物相关肾小球疾病致病抗原的质谱鉴定及发病机制研究”(YXJC2022004)

Analysis of Animal Models of Myasthenia Gravis Based on Its Clinical Characteristics in Chinese and Western Medicine

CHEN Yuhan¹, CHEN Jinling¹, LI Xin²^,³, OU Yanhua²^,³, WANG Si¹, CHEN Jingyi¹, WANG Xingyi¹, YUAN Jiali¹, DUAN Yuanyuan²^,³, YANG Zhongshan¹, NIU Haitao¹^,²^,³()()

^1.Yunnan Key Laboratory of Integrated Traditional Chinese and Western Medicine for Chronic Diseases in Prevention Treatment, Yunnan University of Chinese Medicine, Kunming 650500, China
^2.Key Laboratory of Viral Pathogenesis and Infection Prevention and Control (Jinan University), Ministry of Education, School of Medicine, Jinan University, Guangzhou 510632, China
^3.Guangzhou Key Laboratory of Germ-free Animals and Microbiota Application, Laboratory Animal Center, Jinan University, Guangzhou 510632, China

Received:2024-09-23 Revised:2024-12-31 Published:2025-04-25 Online:2025-04-25
Contact: NIU Haitao (ORCID: 0000-0003-2210-2051), E-mail: htniu@jnu.edu.cn

摘要/Abstract

摘要：

重症肌无力（myasthenia gravis，MG）是一种自身免疫性疾病，主要表现为骨骼肌无力，严重时可累及呼吸功能。目前，西医治疗MG以免疫抑制剂为主，但长期用药的不良反应显著；而中医治疗具有多靶点干预的优势。由于MG的发病机制尚未完全明确，因此建立契合中西医临床特征的动物模型对机制研究及新药开发至关重要。本文系统梳理了MG的中西医病因病机、诊断标准及动物模型研究进展。西医认为MG发病与遗传易感性、环境因素及自身抗体介导的突触后膜损伤密切相关；中医则将其归为“痿证”，病机为先天禀赋不足与后天失养。西医诊断需综合典型症状、疲劳试验、血清抗体检测及电生理检查；中医诊断则以主症结合次症及舌脉辨证分型。现有动物模型以实验性自身免疫性重症肌无力（experimental autoimmune myasthenia gravis，EAMG）和被动转移重症肌无力（passive transfer myasthenia gravis，PTMG）为主。其中，电鳐乙酰胆碱受体（acetylcholine receptor，AChR）诱导的EAMG模型与西医诊断标准吻合度较高，但中医次症吻合度不足；人工合成AChR多肽模型应用广泛，但中医证候吻合度低；肌肉特异性酪氨酸激酶（muscle-specific tyrosine kinase，MuSK）、低密度脂蛋白受体相关蛋白4（low density lipoprotein receptor associated protein 4，LRP4）诱导模型及转基因模型创新性强，但临床吻合度偏低。模型评估需结合行为学、电生理及免疫指标，而中医证候模型尚缺系统性构建。笔者认为，未来研究需融合中医病因学造模法与西医病理机制，构建病证结合模型，并建立基于“以方验证”的中医证候评价体系，结合新兴技术提升模型科学性与实用性。本文将为优化MG动物实验设计、推动中西医结合研究提供理论依据，也为中药复方疗效评价及机制探索奠定基础。

关键词: 重症肌无力, 病证结合, 诊断标准, 动物模型, 吻合度

Abstract:

Myasthenia gravis (MG) is an autoimmune disease characterized primarily by skeletal muscle weakness and, in severe cases, respiratory involvement. Western medical treatment predominantly relies on immunosuppressants, but long-term administration often leads to notable side effects. In contrast, traditional Chinese medicine (TCM) offers the advantage of multi-target interventions. However, the pathogenesis of MG has not been fully elucidated, and the establishment of animal models that accurately reflect the clinical characteristics of both Chinese and Western medicine is essential for mechanism research and new drug development. This paper systematically reviews the etiology and pathogenesis, diagnostic criteria, and progress of animal model research for MG from both Chinese and Western medicine perspectives. In Western medicine, the pathogenesis of MG is closely related to genetic susceptibility, environmental factors, and autoantibody-mediated postsynaptic membrane damage. In TCM, MG is classified under the category of "flaccidity syndrome", attributed to congenital deficiencies and acquired malnourishment. Western diagnostic criteria involve a combination of clinical symptoms, fatigue testing, serum antibody assays, and electrophysiological evaluation. In contrast, TCM diagnosis emphasizes the integration of primary and secondary symptoms with tongue and pulse pattern differentiation. Currently available animal models mainly include experimental autoimmune myasthenia gravis (EAMG) and passive transfer myasthenia gravis (PTMG). The Toredo acetylcholine receptor (AChR) induced EAMG model aligns well with Western diagnostic criteria, but poorly matches secondary symptoms in TCM. The synthetic AChR peptide model is widely used, but shows low conformity with TCM syndromes. Models induced by muscle-specific tyrosine kinase (MuSK), low-density lipoprotein receptor-related protein 4 (LRP4), and transgenic models demonstrate high innovation but exhibit low clinical conformity. Evaluation of these models requires integration of behavioral, electrophysiological, and immunological indicators. However, a systematic framework for modelling TCM syndromes is still lacking. Future research should integrate TCM-based etiological modelling methods with the Western pathological mechanisms to construct disease-syndrome combination models. Additionally, it is crucial to establish a TCM syndrome evaluation system based on "validation by prescription", as well as to improve the scientific rigor and practicality of animal models by the incorporation of emerging technologies. This review provides a theoretical foundation for optimizing MG animal model design, advancing the research on the combination of Chinese and Western medicine, and supporting efficacy assessment and mechanism exploration of Chinese herbal prescriptions.

Key words: Myasthenia gravis, Disease-syndrome combination, Diagnostic criteria, Animal model, Conformity

中图分类号:

R-332

陈钰涵,陈瑾玲,李欣,等. 基于中西医临床病证特点的重症肌无力动物模型分析[J]. 实验动物与比较医学, 2025, 45(2): 176-186. DOI: 10.12300/j.issn.1674-5817.2024.139.

CHEN Yuhan,CHEN Jinling,LI Xin,et al. Analysis of Animal Models of Myasthenia Gravis Based on Its Clinical Characteristics in Chinese and Western Medicine[J]. Laboratory Animal and Comparative Medicine, 2025, 45(2): 176-186. DOI: 10.12300/j.issn.1674-5817.2024.139.

图/表 3

参考文献 54

1	GILHUS N E, TZARTOS S, EVOLI A, et al. Myasthenia gravis[J]. Nat Rev Dis Primers, 2019, 5(1):30. DOI:10.1038/s41572-019-0079-y .
2	BUBUIOC A M, KUDEBAYEVA A, TURUSPEKOVA S, et al. The epidemiology of myasthenia gravis[J]. J Med Life, 2021, 14(1):7-16. DOI:10.25122/jml-2020-0145 .
3	VANOLI F, MANTEGAZZA R. Current drug treatment of myasthenia gravis[J]. Curr Opin Neurol, 2023, 36(5):410-415. DOI:10.1097/WCO.0000000000001196 .
4	盛昭园, 陈建, 应汝炯, 等. 基于海派中医特色的重症肌无力一体化综合诊疗专家共识[J]. 上海中医药杂志, 2024, 58(S1):41-47. DOI: 10.16305/j.1007-1334.2024.08 .
	SHENG Z Y, CHEN J, YING R J, et al. Integrated diagnosis and treatment expert consensus for myasthenia gravis based on characteristics of Shanghai style traditional Chinese medicine[J]. Shanghai J Tradit Chin Med, 2024, 58(S1):41-47. DOI: 10.16305/j.1007-1334.2024.08 .
5	LIU X M, KUANG Y Y, BIAN C R, et al. Exploring the mechanism of action of herbal compounding in the treatment of myasthenia gravis based on network pharmacology[J]. Biotechnol Genet Eng Rev, 2024, 40(2):1164-1179. DOI:10.1080/02648725.2023.2193048 .
6	SANDERSON N S R. Complement and myasthenia gravis[J]. Mol Immunol, 2022, 151:11-18. DOI:10.1016/j.molimm. 2022.08.018 .
7	HONG Y, LIANG X, GILHUS N E. AChR antibodies show a complex interaction with human skeletal muscle cells in a transcriptomic study[J]. Sci Rep, 2020, 10(1):11230. DOI:10.1038/s41598-020-68185-x .
8	SUN S S, SHEN Y H, ZHANG X, et al. The MuSK agonist antibody protects the neuromuscular junction and extends the lifespan in C9orf72-ALS mice[J]. Mol Ther, 2024, 32(7):2176-2189. DOI:10.1016/j.ymthe.2024.05.016 .
9	左瑞, 吕富荣, 王晓燕. 94例重症肌无力患者中医证型分析[J]. 新中医, 2020, 52(17):48-50. DOI: 10.13457/j.cnki.jncm.2020.17.014 .
	ZUO R, LYU F R, WANG X Y. Analysis on Chinese medicine syndrome types of 94 cases of myasthenia gravis[J]. J New Chin Med, 2020, 52(17):48-50. DOI: 10.13457/j.cnki.jncm.2020.17.014 .
10	刘凡, 李国年, 罗贤毅, 等. 结合"年之所加"治疗重症肌无力经验[J]. 山东中医杂志, 2024, 43(7):760-764, 769. DOI: 10.16295/j.cnki.0257-358x.2024.07.018 .
	LIU F, LI G N, LUO X Y, et al. Experience in treating myasthenia gravis combined with "influence of year's circuit Qi"[J]. Shandong J Tradit Chin Med, 2024, 43(7):760-764, 769. DOI: 10.16295/j.cnki.0257-358x.2024.07.018 .
11	张永德, 刘晓艳. 近十年重症肌无力的中医病因病机研究概况[J]. 长春中医药大学学报, 2019, 35(5):995-997. DOI: 10.13463/j.cnki.cczyy.2019.05.050 .
	ZHANG Y D, LIU X Y. Overview of TCM etiology and pathogenesis of myasthenia gravis in recent ten years[J]. J Changchun Univ Chin Med, 2019, 35(5):995-997. DOI: 10.13463/j.cnki.cczyy.2019.05.050 .
12	王宝祥, 许俊杰, 陆霞, 等. 益气托邪汤联合温针灸治疗重症肌无力临床观察[J]. 新中医, 2018, 50(10):166-169. DOI: 10.13457/j.cnki.jncm.2018.10.048 .
	WANG B X, XU J J, LU X, et al. Clinical observation on Yiqi Tuoxie Tang combined with warming needle moxibustion for myasthenia gravis[J]. J New Chin Med, 2018, 50(10):166-169. DOI: 10.13457/j.cnki.jncm.2018.10.048 .
13	曹璐璐, 王炳权, 陈朝远, 等. 李庆和教授运用化湿解毒法治疗重症肌无力经验探析[J]. 西部中医药, 2021, 34(1):34-36. DOI: 10.12174/j.issn.2096-9600.2021.01.09 .
	CAO L L, WANG B Q, CHEN Z Y, et al. Professor Li Qinghe's experience in treating myasthenia gravis by dampness-resolving and detoxifying method[J]. West J Tradit Chin Med, 2021, 34(1):34-36. DOI: 10.12174/j.issn.2096-9600.2021.01.09 .
14	张会永, 冷锦红, 谢伟峰, 等. 张静生治疗重症肌无力临证经验与用药分析[J]. 中华中医药学刊, 2020, 38(12):27-30. DOI: 10.13193/j.issn.1673-7717.2020.12.006 .
	ZHANG H Y, LENG J H, XIE W F, et al. Introduction of ZHANG jingsheng's academic thoughts and prescriptions of myasthenia gravis[J]. Chin Arch Tradit Chin Med, 2020, 38(12):27-30. DOI: 10.13193/j.issn.1673-7717.2020.12.006 .
15	常婷. 中国重症肌无力诊断和治疗指南(2020版)[J]. 中国神经免疫学和神经病学杂志, 2021, 28(1):1-12. DOI: 10.3969/j.issn.1006-2963.2021.01.001 .
	CHANG T. Chinese guidelines for the diagnosis and treatment of myasthenia gravis(2020 version)[J]. Chin J Neuroimmunol Neurol, 2021, 28(1):1-12. DOI: 10.3969/j.issn.1006-2963.2021.01.001 .
16	中国免疫学会神经免疫学分会, 中华医学会神经病学分会神经免疫学组. 重症肌无力诊断和治疗中国专家共识[J]. 中国神经免疫学和神经病学杂志, 2012, 19(6):401-408. DOI: 10.3969/j.issn.1006-2963.2012.06.001 .
	Chinese Society of Immunology Neuroimmunology Branch, Chinese Medical Association Neurology Branch Neuroimmunology Group. Chinese expert consensus on the diagnosis and treatment of myasthenia gravis[J].Chin J Neuroimmunol Neurol, 2012, 19(6):401-408. DOI: 10.3969/j.issn.1006-2963.2012.06.001 .
17	佚名. «中医内科常见病诊疗指南»发布[J]. 中华中医药杂志, 2008, 23(9):848.
	Anon. Guidelines for diagnosis and treatment of common diseases in internal medicine of traditional Chinese medicine issued[J]. China J Tradit Chin Med Pharm, 2008, 23(9):848.
18	李广文, 庞松, 方雪, 等. 重症肌无力中医辨证分型研究[J]. 内蒙古中医药, 2016, 35(7):86-87. DOI: 10.16040/j.cnki.cn15-1101.2016.07.086 .
	LI G W, PANG S, FANG X, et al. Study on dialectical differentiation of myasthenia gravis in traditional Chinese medicine[J]. Nei Mongol J Tradit Chin Med, 2016, 35(7):86-87. DOI: 10.16040/j.cnki.cn15-1101.2016.07.086 .
19	姚舜禹, 薛雅慧, 杜妙乔, 等. 重症肌无力的动物模型研究进展[J]. 国际神经病学神经外科学杂志, 2024, 51(1):79-85. DOI: 10.16636/j.cnki.jinn.1673-2642.2024.01.014 .
	YAO S Y, XUE Y H, DU M Q, et al. Advances in the research on animal models for myasthenia gravis[J]. J Int Neurol Neurosurg, 2024, 51(1):79-85. DOI: 10.16636/j.cnki.jinn.1673-2642.2024.01.014 .
20	JIAO W, HU F Y, LI J Q, et al. Qiangji Jianli Decoction promotes mitochondrial biogenesis in skeletal muscle of myasthenia gravis rats via AMPK/PGC-1α signaling pathway[J]. Biomed Pharmacother, 2020, 129:110482. DOI:10.1016/j.biopha.2020.110482 .
21	BORGES L S, RICHMAN D P. Muscle-specific kinase myasthenia gravis[J]. Front Immunol, 2020, 11:707. DOI:10.3389/fimmu.2020.00707 .
22	CHU Y Y, HE Y H, ZHAI W Z, et al. CpG adjuvant enhances humoral and cellular immunity against OVA in different degrees in BALB/c, C57BL/6J, and C57BL/6N mice[J]. Int Immunopharmacol, 2024, 138:112593. DOI:10.1016/j.intimp.2024.112593 .
23	BOGATIKOV E, LINDBLAD I, PUNGA T, et al. miR-1933-3p is upregulated in skeletal muscles of MuSK+ EAMG mice and affects Impa1 and Mrpl27[J]. Neurosci Res, 2020, 151:46-52. DOI:10.1016/j.neures.2019.02.003 .
24	WANG K C, XIE Y Y, CHEN X X, et al. The activation of muscarinic acetylcholine receptors protects against neuroinflammation in a mouse model through attenuating microglial inflammation[J]. Int J Mol Sci, 2024, 25(19):10432. DOI:10.3390/ijms251910432 .
25	DRESSER L, WLODARSKI R, REZANIA K, et al. Myasthenia gravis: epidemiology, pathophysiology and clinical manifestations[J]. J Clin Med, 2021, 10(11):2235. DOI:10.3390/jcm10112235 .
26	KUSNER L L, LE PANSE R, LOSEN M, et al. Animal models of myasthenia gravis for preclinical evaluation[M]//Myasthenia gravis and related disorders. Cham: Springer International Publishing, 2018:61-70. DOI:10.1007/978-3-319-73585-6_4 .
27	徐添, 官磊瑶, 刘浪辉, 等. 基于数据挖掘的重症肌无力动物模型应用分析[J]. 江西中医药大学学报, 2023, 35(6):92-97.
	XU T, GUAN L Y, LIU L H, et al. Application analysis of myasthenia gravis animal model based on data mining[J]. J Jiangxi Univ Chin Med, 2023, 35(6):92-97.
28	HUA Y, JIANG P P, DAI C Y, et al. Extracellular vesicle autoantibodies[J]. J Autoimmun, 2024, 149:103322. DOI:10.1016/j.jaut.2024.103322 .
29	LAZARIDIS K, BALTATZIDI V, TRAKAS N, et al. Characterization of a reproducible rat EAMG model induced with various human acetylcholine receptor domains[J]. J Neuroimmunol, 2017, 303:13-21. DOI:10.1016/j.jneuroim. 2016.12.011 .
30	YU Z, ZHANG M Y, JING H Y, et al. Characterization of LRP4/agrin antibodies from a patient with myasthenia gravis[J]. Neurology, 2021, 97(10): e975-e987. DOI:10.1212/WNL. 0000000000012463 .
31	唐毅华, 章正祥, 李净娅, 等. 重症肌无力模型的研究进展[J]. 浙江临床医学, 2018(11):1886-1888.
	TANG Y H, ZHANG Z X, LI J Y, et al. Advances in modelling myasthenia gravis[J]. Zhejiang Clin Med J, 2018(11):1886-1888.
32	KUSNER L L, LOSEN M, VINCENT A, et al. Guidelines for pre-clinical assessment of the acetylcholine receptor: specific passive transfer myasthenia gravis model-Recommendations for methods and experimental designs[J]. Exp Neurol, 2015, 270:3-10. DOI:10.1016/j.expneurol.2015.02.025 .
33	CRON M A, PAYET C A, FAYET O M, et al. Decreased expression of miR-29 family associated with autoimmune myasthenia gravis[J]. J Neuroinflammation, 2020, 17(1):294. DOI:10.1186/s12974-020-01958-3 .
34	GAO X L, WEN Y J, WANG Z, et al. Rapamycin alleviates the symptoms of experimental autoimmune myasthenia gravis rats by down-regulating Th17 cell/regulatory T cell ratio[J]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi, 2021, 37(1):24-30.
35	FUCHS S, ARICHA R, REUVENI D, et al. Experimental autoimmune myasthenia gravis (EAMG): from immunochemical characterization to therapeutic approaches[J]. J Autoimmun, 2014, 54:51-59. DOI:10.1016/j.jaut.2014.06.003 .
36	THEISSEN L T, SCHROETER C B, HUNTEMANN N, et al. Recombinant acetylcholine receptor immunization induces a robust model of experimental autoimmune myasthenia gravis in mice[J]. Cells, 2024, 13(6):508. DOI:10.3390/cells13060508 .
37	LI X L, LI H, ZHANG M, et al. Correction to: Exosomes derived from atorvastatin-modified bone marrow dendritic cells ameliorate experimental autoimmune myasthenia gravis by up-regulated levels of IDO/Treg and partly dependent on FasL/Fas pathway[J]. J Neuroinflammation, 2019, 16(1):119. DOI:10.1186/s12974-019-1503-7 .
38	MANTEGAZZA R, CORDIGLIERI C, CONSONNI A, et al. Animal models of myasthenia gravis: utility and limitations[J]. Int J Gen Med, 2016, 9:53-64. DOI:10.2147/IJGM.S88552 .
39	ALABBAD S, ALGAEED M, SIKORSKI P, et al. Monoclonal antibody-based therapies for myasthenia gravis[J]. BioDrugs, 2020, 34(5):557-566. DOI:10.1007/s40259-020-00443-w .
40	NORIDOMI K, WATANABE G, HANSEN M N, et al. Structural insights into the molecular mechanisms of myasthenia gravis and their therapeutic implications[J]. eLife, 2017, 6: e23043. DOI:10.7554/eLife.23043 .
41	ITO R, TAKAHASHI T, KATANO I, et al. Current advances in humanized mouse models[J]. Cell Mol Immunol, 2012, 9(3):208-214. DOI:10.1038/cmi.2012.2 .
42	CHHATTA A, MIKKERS H M M, STAAL F J T. Strategies for Thymus regeneration and generating thymic organoids[J]. J Immunol Regen Med, 2021, 14: 100052. DOI:10.1016/j.regen.2021.100052 .
43	BRISSOT E, LABOPIN M, LABUSSIÈRE H, et al. Post-transplant cyclophosphamide versus anti-thymocyte globulin after reduced intensity peripheral blood allogeneic cell transplantation in recipients of matched sibling or 10/10 HLA matched unrelated donors: final analysis of a randomized, open-label, multicenter, phase 2 trial[J]. Blood Cancer J, 2024, 14(1):31. DOI:10.1038/s41408-024-00990-3 .
44	PUNGA A R, LIN S, OLIVERI F, et al. Muscle-selective synaptic disassembly and reorganization in MuSK antibody positive MG mice[J]. Exp Neurol, 2011, 230(2):207-217. DOI:10.1016/j.expneurol.2011.04.018 .
45	COLE R N, GHAZANFARI N, NGO S T, et al. Patient autoantibodies deplete postsynaptic muscle-specific kinase leading to disassembly of the ACh receptor scaffold and myasthenia gravis in mice[J]. J Physiol, 2010, 588(Pt17):3217-3229. DOI:10.1113/jphysiol.2010.190298 .
46	KLOOSTER R, PLOMP J J, HUIJBERS M G, et al. Muscle-specific kinase myasthenia gravis IgG4 autoantibodies cause severe neuromuscular junction dysfunction in mice[J]. Brain, 2012, 135(Pt 4):1081-1101. DOI:10.1093/brain/aws025 .
47	RICHMAN D P, NISHI K, FERNS M J, et al. Animal models of antimuscle-specific kinase myasthenia[J]. Ann N Y Acad Sci, 2012, 1274:140-147. DOI:10.1111/j.1749-6632.2012.06782.x .
48	HOMMA M, UZAWA A, TANAKA H, et al. A novel fusion protein, Ach Receptor-fc, ameliorates myasthenia gravis by neutralizing antiacetylcholine receptor antibodies and suppressing acetylcholine receptor-reactive B cells[J]. Neurotherapeutics, 2017, 14(1):191-198. DOI:10.1007/s13311-016-0476-9 .
49	NIU L X, GUO C Y, HAO Z B, et al. Potential roles of recombinant acetylcholine receptor α subunit 1-211 in immunoadsorbent and DNA immunization[J]. J Immunol Methods, 2011, 372(1-2):14-21. DOI:10.1016/j.jim.2011.04.015 .
50	BISPO E C I, ARGAÑARAZ E R, NEVES F A R, et al. Immunomodulatory effect of IFN-γ licensed adipose-mesenchymal stromal cells in an in vitro model of inflammation generated by SARS-CoV-2 antigens[J]. Sci Rep, 2024, 14(1):24235. DOI:10.1038/s41598-024-75776-5 .
51	STASSEN M H W, MENG F P, MELGERT E, et al. Experimental autoimmune myasthenia gravis in mice expressing human immunoglobulin loci[J]. J Neuroimmunol, 2003, 135(1-2):56-61. DOI:10.1016/s0165-5728(02)00436-8 .
52	ULUSOY C, ÇAVUŞ F, YıLMAZ V, et al. Immunization with recombinantly expressed LRP4 induces experimental autoimmune myasthenia gravis in C57BL/6 mice[J]. Immunol Invest, 2017, 46(5):490-499. DOI:10.1080/08820139. 2017. 1299754 .
53	LOSEN M, MARTINEZ-MARTINEZ P, MOLENAAR P C, et al. Standardization of the experimental autoimmune myasthenia gravis (EAMG) model by immunization of rats with Torpedo californica acetylcholine receptors: Recommendations for methods and experimental designs[J]. Exp Neurol, 2015, 270:18-28. DOI:10.1016/j.expneurol. 2015. 03.010 .
54	杨俊超, 文颖娟. 重症肌无力实验动物模型的研究进展[J]. 医学综述, 2015, 21(19):3466-3469. DOI: 10.3969/j.issn.1006-2084.2015.19.004 .
	YANG J C, WEN Y J. Research progress of myasthenia gravis experimental animal models[J]. Med Recapitul, 2015, 21(19):3466-3469. DOI: 10.3969/j.issn.1006-2084.2015.19.004 .

序号 Number	指标分类 Classification of indicators	临床表现 Clinical manifestation
①	典型临床特征（20%）	局部或全身肌群出现波动性疲劳无力，且在休息后稍有减轻
②	临床试验（20%）	让受累肌群进行持续活动后，肌肉无力症状加重即为疲劳试验阳性；冰敷受累肌群，肌无力症状明显减轻与改善即为冰敷试验阳性
③	药理学检查（15%）	肌内注射胆碱酯酶抑制剂甲基硫酸新斯的明后，以改善最显著时的单项绝对分数计算相对评分，各单项相对评分有一项为阳性者，即为新斯的明试验阳性
④	电生理检查（15%）	采用低频重复电刺激神经干，波幅衰减10%以上为阳性；单纤维肌电图测定“颤抖”研究神经-肌肉传递功能，“颤抖”增宽或阻滞为阳性
⑤	血清学抗体检测（15%）	可以检测到AChR抗体阳性或者Titin抗体阳性，极少部分可以检测到MuSK抗体阳性或者LRP4抗体阳性
⑥	胸腺影像学检查（15%）	胸腺CT提示胸腺增生或胸腺瘤

序号 Number	指标分类 Classification of indicators	临床表现 Clinical manifestation
①	典型临床特征（20%）	局部或全身肌群出现波动性疲劳无力，且在休息后稍有减轻
②	临床试验（20%）	让受累肌群进行持续活动后，肌肉无力症状加重即为疲劳试验阳性；冰敷受累肌群，肌无力症状明显减轻与改善即为冰敷试验阳性
③	药理学检查（15%）	肌内注射胆碱酯酶抑制剂甲基硫酸新斯的明后，以改善最显著时的单项绝对分数计算相对评分，各单项相对评分有一项为阳性者，即为新斯的明试验阳性
④	电生理检查（15%）	采用低频重复电刺激神经干，波幅衰减10%以上为阳性；单纤维肌电图测定“颤抖”研究神经-肌肉传递功能，“颤抖”增宽或阻滞为阳性
⑤	血清学抗体检测（15%）	可以检测到AChR抗体阳性或者Titin抗体阳性，极少部分可以检测到MuSK抗体阳性或者LRP4抗体阳性
⑥	胸腺影像学检查（15%）	胸腺CT提示胸腺增生或胸腺瘤

[1]	连辉, 姜艳玲, 刘佳, 张玉立, 谢伟, 薛晓鸥, 李健. 异常子宫出血大鼠模型的构建与评价[J]. 实验动物与比较医学, 2025, 45(2): 130-146.
[2]	罗世雄, 张赛, 陈慧. 常见哮喘动物模型的建立方法与评价研究进展[J]. 实验动物与比较医学, 2025, 45(2): 167-175.
[3]	王碧莹, 鲁家铄, 昝桂影, 陈若松, 柴景蕊, 刘景根, 王瑜珺. 啮齿类动物药物成瘾模型的构建方法和应用进展[J]. 实验动物与比较医学, 2025, 45(2): 158-166.
[4]	费彬, 郭文科, 郭建平. 疝疾病动物模型研究及新型疝修补材料应用进展[J]. 实验动物与比较医学, 2025, 45(1): 55-66.
[5]	杨家豪, 丁纯蕾, 钱风华, 孙旗, 姜旭升, 陈雯, 沈梦雯. 脓毒症相关脏器损伤动物模型研究进展[J]. 实验动物与比较医学, 2024, 44(6): 636-644.
[6]	孙效容, 苏丹, 贵文娟, 陈玥. 手术诱导大鼠中重度膝骨关节炎模型的建立与评价[J]. 实验动物与比较医学, 2024, 44(6): 597-604.
[7]	田芳, 潘滨, 史佳怡, 徐燕意, 李卫华. 大气细颗粒物PM_2.5暴露动物模型建立方法及在生殖毒性研究中的应用进展[J]. 实验动物与比较医学, 2024, 44(6): 626-635.
[8]	赵小娜, 王鹏, 叶茂青, 曲新凯. 应用Triacsin C构建新型高血糖肥胖小鼠心功能减退模型[J]. 实验动物与比较医学, 2024, 44(6): 605-612.
[9]	涂颖欣, 纪依澜, 王菲, 杨东明, 王冬冬, 孙芷馨, 戴悦欣, 王言吉, 阚广捍, 吴斌, 赵德明, 杨利峰. 小型猪后肢去负荷模拟失重模型的建立与组织损伤研究[J]. 实验动物与比较医学, 2024, 44(5): 475-486.
[10]	黄冬妍, 吴建辉. 生殖毒理学研究动物模型的建立方法及应用评价[J]. 实验动物与比较医学, 2024, 44(5): 550-559.
[11]	郑艺清, 邓亚胜, 范燕萍, 梁天薇, 黄慧, 刘永辉, 倪召兵, 林江. 基于数据挖掘的盆腔炎性疾病动物模型应用分析[J]. 实验动物与比较医学, 2024, 44(4): 405-418.
[12]	吴玥, 李璐, 张阳, 王珏, 冯婷婷, 李依桐, 王凯, 孔琪. 冠状病毒感染动物模型组学数据集成分析[J]. 实验动物与比较医学, 2024, 44(4): 357-373.
[13]	丁天送, 谢京红, 杨斌, 李河桥, 乔一倬, 陈心如, 田纹凡, 李佳佩, 张婉怡, 李帆旋. 复发性流产动物模型特点评价与应用分析[J]. 实验动物与比较医学, 2024, 44(4): 393-404.
[14]	姚广源, 董平, 吴昊, 柏梅, 党嬴, 王悦, 胡凯. 长骨骨折动物模型的研究进展[J]. 实验动物与比较医学, 2024, 44(3): 289-296.
[15]	包方奇, 屠海烨, 方明笋, 张倩, 陈民利. 基于动物模型的高尿酸肾病病理及分子机制研究进展[J]. 实验动物与比较医学, 2024, 44(2): 180-191.

基于中西医临床病证特点的重症肌无力动物模型分析

Analysis of Animal Models of Myasthenia Gravis Based on Its Clinical Characteristics in Chinese and Western Medicine

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

图/表 3

参考文献 54

相关文章 15

编辑推荐

Metrics

本文评价