Laboratory Animal and Comparative Medicine ›› 2025, Vol. 45 ›› Issue (2): 176-186.DOI: 10.12300/j.issn.1674-5817.2024.139
• Animal Models of Human Diseases • Previous Articles Next Articles
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()(
)
Received:
2024-09-23
Revised:
2024-12-31
Online:
2025-04-25
Published:
2025-05-12
Contact:
NIU Haitao
CLC Number:
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.
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URL: https://www.slarc.org.cn/dwyx/EN/10.12300/j.issn.1674-5817.2024.139
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 |
Table 1 Western medical diagnostic criteria for myasthenia gravis
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 |
辨证分型 Syndrome differentiation | 主证 Main syndrome | 次证 Secondary syndrome | 舌脉 Pulse and tongue |
---|---|---|---|
脾胃气虚证 Spleen and stomach qi deficiency syndrome | ① 上胞下垂,视歧; ② 肢体痿软无力; ③ 言语謇涩、咀嚼和吞咽困难 | ① 神疲乏力; ② 胸闷气短; ③ 纳呆;④ 便溏或排便无力; ⑤ 面色萎黄; ⑥ 脘腹痞胀 | 舌淡、苔薄白、脉细弱 |
脾肾两虚证 Spleen and kidney deficiency syndrome | ① 上胞下垂; ② 四肢倦怠无力; ③ 吞咽困难,口齿不清 | 偏阴虚: ① 腰膝酸软; ② 自汗或盗汗; ③ 口干咽燥,五心烦热; ④ 纳差; ⑤ 小便色黄,大便干结。 偏阳虚: ① 腰膝酸软,腹部冷; ② 下利清谷; ③ 畏寒身冷; ④ 小便清长夜尿多,大便稀溏 | 偏阴虚:舌红,少苔,脉细数; 偏阳虚:舌质淡胖,苔淡胖,脉沉迟少力 |
肝肾亏虚证 Liver and kidney deficiency syndrome | ① 上胞下垂、复视或斜视或视物不清; ② 肌肉萎缩 | ① 五心烦热,目干涩,口干咽燥; ② 乏力; ③ 音喑; ④ 头晕、耳鸣; ⑤ 腰膝酸软; ⑥ 肌萎缩; ⑦ 遗精或月经不调 | 舌红、苔薄或无苔、脉细数 |
气血亏虚证 Qi and blood deficiency syndrome | ① 上胞下垂; ② 四肢软弱无力或全身无力,行动困难 | ① 面色无华; ② 神疲乏力; ③ 气短声低; ④ 心悸; ⑤ 自汗 | 舌淡、苔薄白、脉细弱 |
肺脾气虚证 Lung and spleen qi deficiency syndrome | ① 上胞下垂; ② 肢体痿软无力 | ① 咳嗽; ② 痰多; ③ 易感冒; ④ 自汗或盗汗 | 舌淡、苔白、脉细弱 |
瘀血阻络证 Blood-stasis obstruction syndrome | ①上胞下垂、复视或斜视; ②行动不便 | ① 眼球活动不灵; ② 畏光; ③ 消瘦 | 舌暗淡、苔少、脉弦细 |
大气下陷证 Pectoral qi collapse syndrome | ① 上胞下垂; ② 颈软头倾,全身无力; ③ 吞咽困难,构音困难; ④ 呼吸困难 | ① 喘脱; ② 汗出频频; ③ 咳痰无力或不能; ④ 唇甲发绀; ⑤ 重者不能平卧,甚至俯仰难合; ⑥ 精神烦躁; ⑦ 呼吸急促张口抬肩,危重期则呼吸微弱表浅;⑧ 意识障碍 | 舌质淡或暗,舌体胖大或有齿痕,苔薄白或少苔或黄厚腻,脉滑数或脉沉细或沉细尺弱 |
湿邪困脾证 Dampness traps the spleen syndrome | ① 上胞下垂,眼胞肿胀; ② 肢体倦怠无力困重 | ① 胸膈痞闷; ② 面晦纳垢; ③ 纳呆便溏 | 舌胖大,苔白腻,舌边有齿痕,脉濡缓或滑 |
Table 2 Syndrome differentiation of myasthenia gravis in traditional Chinese medicine
辨证分型 Syndrome differentiation | 主证 Main syndrome | 次证 Secondary syndrome | 舌脉 Pulse and tongue |
---|---|---|---|
脾胃气虚证 Spleen and stomach qi deficiency syndrome | ① 上胞下垂,视歧; ② 肢体痿软无力; ③ 言语謇涩、咀嚼和吞咽困难 | ① 神疲乏力; ② 胸闷气短; ③ 纳呆;④ 便溏或排便无力; ⑤ 面色萎黄; ⑥ 脘腹痞胀 | 舌淡、苔薄白、脉细弱 |
脾肾两虚证 Spleen and kidney deficiency syndrome | ① 上胞下垂; ② 四肢倦怠无力; ③ 吞咽困难,口齿不清 | 偏阴虚: ① 腰膝酸软; ② 自汗或盗汗; ③ 口干咽燥,五心烦热; ④ 纳差; ⑤ 小便色黄,大便干结。 偏阳虚: ① 腰膝酸软,腹部冷; ② 下利清谷; ③ 畏寒身冷; ④ 小便清长夜尿多,大便稀溏 | 偏阴虚:舌红,少苔,脉细数; 偏阳虚:舌质淡胖,苔淡胖,脉沉迟少力 |
肝肾亏虚证 Liver and kidney deficiency syndrome | ① 上胞下垂、复视或斜视或视物不清; ② 肌肉萎缩 | ① 五心烦热,目干涩,口干咽燥; ② 乏力; ③ 音喑; ④ 头晕、耳鸣; ⑤ 腰膝酸软; ⑥ 肌萎缩; ⑦ 遗精或月经不调 | 舌红、苔薄或无苔、脉细数 |
气血亏虚证 Qi and blood deficiency syndrome | ① 上胞下垂; ② 四肢软弱无力或全身无力,行动困难 | ① 面色无华; ② 神疲乏力; ③ 气短声低; ④ 心悸; ⑤ 自汗 | 舌淡、苔薄白、脉细弱 |
肺脾气虚证 Lung and spleen qi deficiency syndrome | ① 上胞下垂; ② 肢体痿软无力 | ① 咳嗽; ② 痰多; ③ 易感冒; ④ 自汗或盗汗 | 舌淡、苔白、脉细弱 |
瘀血阻络证 Blood-stasis obstruction syndrome | ①上胞下垂、复视或斜视; ②行动不便 | ① 眼球活动不灵; ② 畏光; ③ 消瘦 | 舌暗淡、苔少、脉弦细 |
大气下陷证 Pectoral qi collapse syndrome | ① 上胞下垂; ② 颈软头倾,全身无力; ③ 吞咽困难,构音困难; ④ 呼吸困难 | ① 喘脱; ② 汗出频频; ③ 咳痰无力或不能; ④ 唇甲发绀; ⑤ 重者不能平卧,甚至俯仰难合; ⑥ 精神烦躁; ⑦ 呼吸急促张口抬肩,危重期则呼吸微弱表浅;⑧ 意识障碍 | 舌质淡或暗,舌体胖大或有齿痕,苔薄白或少苔或黄厚腻,脉滑数或脉沉细或沉细尺弱 |
湿邪困脾证 Dampness traps the spleen syndrome | ① 上胞下垂,眼胞肿胀; ② 肢体倦怠无力困重 | ① 胸膈痞闷; ② 面晦纳垢; ③ 纳呆便溏 | 舌胖大,苔白腻,舌边有齿痕,脉濡缓或滑 |
模型类型 Model types | 动物 Animal | 造模方法及原理 Modeling method and principle | 模型优缺点 Model advantages and disadvantages | 与临床病证特点的吻合度 Conformity with clinical disease characteristics |
---|---|---|---|---|
电鳐AChR诱导的EAMG模型 AChR-induced EAMG model using the electric ray | Lewis大鼠 | 从电鳐的电器官分离纯化AChR后,与含有结核分枝杆菌的弗氏完全佐剂(Freund’s complete adjuvant,FCA)充分混合,在实验大鼠的足垫、腹部及背部皮下多点注射乳剂。用类似方法再行2~3次增强免疫[ | 优点为典型模型,成模率高,可行性强,与人类的发病进程相似度高[ 缺点为操作复杂、制备成本高、不易推广,同时成模后在选择合适干预治疗MG的时间窗方面存在困难[ | 符合西医的有①、 ②、③、④、⑤,吻 合度85%; 符合中医主证的有①、③、⑤; 符合中医次证的有⑥,总体吻合度50% |
人工合成AChR多肽构建的EAMG模型 Model of AChR-induced EAMG using synthetic AChR peptide | Lewis大鼠 | 将人工合成的肽段(一般常用肽段为α97~116以及α129~145肽段)与等量FCA充分混匀制成乳剂于大鼠手足垫多点注射,一个月后加强免疫一次[ | 优点为操作简单,方法简便,成本相对低,模型易于复制,成模率高,且该模型有利于MG发病机制和治疗药物的研究[ 缺点为实验周期较长、表现的肌无力症状较轻[ | 符合西医:的有①、②、③、④、⑤,吻合度85%; 符合中医主症的有①、③、⑤; 符合中医次症的有⑥,总体吻合度50% |
被动转移EAMG鼠血清中的AChR-Ab建立的PTMG模型 Model of PTMG by passive transfer of AChR-Ab in the serum of EAMG rats | Lewis大鼠 | 从EAMG大鼠血清中获得IgG,将抗体稀释于生理盐水后,注射到大鼠颈静脉中[ | 优点为成模率高,成模速度快,适合短期快速实验; 缺点为因为需要已成模的EAMG大鼠,因此不适合首次实验。而且该模型维持肌无力的症状时间短,不适合长期实验 | 符合西医的有①、③、④、⑤,吻合度65%; 符合中医主症的有 ①、③、⑤,吻合度 45% |
用MG患者血清及血清内成分建立PTMG模型 Model of PTMG with serum and intraserum components from MG patients | BALB/c 小鼠 | 收集未使用过激素治疗的AChR-Ab阳性和阴性的MG患者血液,分离血清后以每次0.8 mL注射小鼠,连续7 d,在初次注射血清后24 h后,再腹腔注射环磷酰胺300 mg/kg。通过使用该方法,使小鼠获得MG的病理特征 | 优点为造模时间短,制备成本低,制备方法简单,适合短期研究; 缺点为血清来源难以获得,患者存在异质性,模型结果评定以及实验标准化困难,同时血清中存在各种免疫蛋白及炎症介质,不能保证单因素影响 | 符合西医的有①、③、④、⑥,吻合度65%; 符合中医主症的有③、⑤; 符合中医次症的有⑤、⑥,总体吻合度40% |
利用杂交瘤细胞株制备单克隆抗体建立PTMG模型 Establishment of a PTMG model using hybridoma cell lines for the preparation of monoclonal antibodies | Lewis大鼠 | AChR单抗mAb35/mAbA7/mAbG10杂交瘤细胞株腹腔注射[ | 优点为建模时间短,发病率高,易于评估,适合进行短期研究 | 符合西医的有①、③、⑤,吻合度50%; 符合中医主症的有①、③、⑤,吻合度45% |
向实验动物脑室中注入MG患者AChR-Ab建立PTMG模型 Establishment of a PTMG model by injection of AChR-Ab from MG patients into the brain ventricles of experimental animals | SD大鼠 | 收集MG患者血清提取AChR-Ab,将其注入大鼠侧脑室,隔日重复,共3次。大约2周后建立CNS损害的大鼠模型[ | 优点为该模型的建立为阐明MG 中枢神经系统损害的机制提供依据; 缺点为操作复杂且难度高,同时对实验环境与条件要求严格 | 符合西医的有①、③、④、⑤,吻合度65%; 符合中医主症的有③; 符合中医次症的有⑥,总体吻合度20% |
通过MG患者胸腺组织移植建立PTMG模型 Establishment of a PTMG model by thymus tissue transplantation from MG patients | NOD/ SCID 小鼠 | 将 MG 患者的完整胸腺组织移植到严重联合免疫缺陷小鼠(NOD/SCID)小鼠肾被膜下[ | 优点为该方法为胸腺致敏机制打下基石; 缺点为胸腺细胞虽然参与了MG的发病过程,但不是MG唯一的致病因素 | 符合西医的有①、③、④、⑥,吻合度65%; 符合中医主症的有③; 符合中医次症的有⑥,总体吻合度20% |
通过移植MG患者外周淋巴细胞建立PTMG模型 Establishment of a PTMG model by transplantation of peripheral lymphocytes from MG patients | NOD/ SCID 小鼠 | 将MG患者血淋巴细胞进行腹腔注入NOD/SCID小鼠体内[ | 优点为CD4+T细胞在MG发病中的作用提供了依据 | 符合西医的有①、④、⑤,吻合度50%; 符合中医主症的有⑤; 符合中医次症的有⑥,总体吻合度20% |
MuSK诱导的EAMG模型 MuSK-induced EAMG model | C57BL/6J小鼠或Lewis大鼠 | 以大鼠MuSK基因编码序列为模板合成小鼠MuSK抗原,采取主动免疫法将小鼠MuSK与FCA混合制成抗原乳剂,通过尾静脉或腹腔注射入小鼠体内,28 d后重复注射一次[ | 缺点为MuSK抗体介导的MG的具体机制尚未完全明确,动物模型还处于研究阶段,且与AChR诱导的模型相比,发病率偏低且模型不成熟 | 符合西医的有①、③、④、⑤,吻合度65%; 符合中医主症的有①、③、⑤,总体吻合度45% |
重组人AChR建立EAMG模型 Recombinant human AChR modelling of EAMG | Lewis大鼠 | 将人工合成的人AChR α亚基1~210片段通过质粒转染的方法获得融合蛋白,并将其与等体积FCA制成乳剂,于大鼠肩背足垫等处多点注射[ | 优点为成模率高,免疫原充足,操作简便,成本低廉 | 符合西医的有①、③、⑤,吻合度50%; 符合中医主症的有①、③、⑤; 符合中医次症的有⑥,总体吻合度50% |
采用核酸疫苗建立EAMG模型 Modelling EAMG using nucleic acid vaccines | C57BL/6J小鼠[ | 核酸疫苗通过将克隆靶抗原编码的基因或DNA片段加入到如质粒、噬菌体等载体中去,然后向实验动物体内注入重组后的载体,而使得机体表达靶抗原基因,从而激活机体的免疫系统,产生相应的体液和细胞免疫。可以诱导小鼠的免疫系统识别并产生针对AChR的抗体,从而模拟MG的病理过程 | 优点为免疫原性好,可以产生较强的持久性免疫应答; 缺点为表现出的肌无力症状不严重,操作困难,同时该造模技术方法尚在探索和完善阶段 | 符合西医的有①、⑤,吻合度35%; 符合中医主症的有③,总体吻合度15% |
利用转基因小鼠神经肌肉接头局部产生的IFN-γ建立EAMG模型 Establishment of an EAMG model using locally produced IFN-γ in transgenic mice neuromuscular junction | BALB/c 小鼠 | 将鼠IFN-γ基因与调节性片段——鼠nAChRε基因融合,构建DNA质粒,植入小鼠卵母细胞,使新生小鼠在神经接头处表达该基因并产生IFN-γ[ | 优点为该模型为探索研究性模型,证明了MG的发病与IFN-γ有关,表现出的症状以及指标与人类MG相似度高; 缺点为典型性不足,操作复杂有难度 | 符合西医的有①、③、④、⑤,吻合度65%; 符合中医主症的有①、③、⑤; 符合中医次症的有⑤、⑥,总体吻合度55% |
利用人免疫球蛋白转基因小鼠构建EAMG模型 Construction of an EAMG model using human immunoglobulin transgenic mice | C57BL/6J小鼠 | 建立了表达人免疫球蛋白的转基因小鼠,并将由电鳐电器官提纯的AChR与FCA一起,于第0、3、5 周皮下注射该小鼠[ | 优点为该模型产生的抗体均为人源性抗体,在免疫学上更接近人MG; 缺点为成本高,操作难,模型尚未成熟 | 符合西医的有①、③、④、⑤,吻合度65%; 符合中医主症的有①、③、⑤; 符合中医次症的有⑤、⑥,总体吻合度55% |
LRP4诱导的EAMG模型 Model of LRP4-induced EAMG | C57BL/6小鼠 | 通过单体集聚蛋白与LRP4相互作用形成二元复合物,协同LRP4诱导的MG模型促进四聚体形成,从而影响运动神经元末梢释放集聚蛋白诱导的AChR聚集[ | 优点为该模型为研究探索性模型,为LRP4参与MG发病提供了依据; 缺点为成本高,模型稳定性不足 | 符合西医的有①、③、④,吻合度50%; 符合中医主症的有③,总体吻合度15% |
Table 3 Analysis of the conformity between common animal models of myasthenia gravis and clinical symptoms in Chinese and Western medicine
模型类型 Model types | 动物 Animal | 造模方法及原理 Modeling method and principle | 模型优缺点 Model advantages and disadvantages | 与临床病证特点的吻合度 Conformity with clinical disease characteristics |
---|---|---|---|---|
电鳐AChR诱导的EAMG模型 AChR-induced EAMG model using the electric ray | Lewis大鼠 | 从电鳐的电器官分离纯化AChR后,与含有结核分枝杆菌的弗氏完全佐剂(Freund’s complete adjuvant,FCA)充分混合,在实验大鼠的足垫、腹部及背部皮下多点注射乳剂。用类似方法再行2~3次增强免疫[ | 优点为典型模型,成模率高,可行性强,与人类的发病进程相似度高[ 缺点为操作复杂、制备成本高、不易推广,同时成模后在选择合适干预治疗MG的时间窗方面存在困难[ | 符合西医的有①、 ②、③、④、⑤,吻 合度85%; 符合中医主证的有①、③、⑤; 符合中医次证的有⑥,总体吻合度50% |
人工合成AChR多肽构建的EAMG模型 Model of AChR-induced EAMG using synthetic AChR peptide | Lewis大鼠 | 将人工合成的肽段(一般常用肽段为α97~116以及α129~145肽段)与等量FCA充分混匀制成乳剂于大鼠手足垫多点注射,一个月后加强免疫一次[ | 优点为操作简单,方法简便,成本相对低,模型易于复制,成模率高,且该模型有利于MG发病机制和治疗药物的研究[ 缺点为实验周期较长、表现的肌无力症状较轻[ | 符合西医:的有①、②、③、④、⑤,吻合度85%; 符合中医主症的有①、③、⑤; 符合中医次症的有⑥,总体吻合度50% |
被动转移EAMG鼠血清中的AChR-Ab建立的PTMG模型 Model of PTMG by passive transfer of AChR-Ab in the serum of EAMG rats | Lewis大鼠 | 从EAMG大鼠血清中获得IgG,将抗体稀释于生理盐水后,注射到大鼠颈静脉中[ | 优点为成模率高,成模速度快,适合短期快速实验; 缺点为因为需要已成模的EAMG大鼠,因此不适合首次实验。而且该模型维持肌无力的症状时间短,不适合长期实验 | 符合西医的有①、③、④、⑤,吻合度65%; 符合中医主症的有 ①、③、⑤,吻合度 45% |
用MG患者血清及血清内成分建立PTMG模型 Model of PTMG with serum and intraserum components from MG patients | BALB/c 小鼠 | 收集未使用过激素治疗的AChR-Ab阳性和阴性的MG患者血液,分离血清后以每次0.8 mL注射小鼠,连续7 d,在初次注射血清后24 h后,再腹腔注射环磷酰胺300 mg/kg。通过使用该方法,使小鼠获得MG的病理特征 | 优点为造模时间短,制备成本低,制备方法简单,适合短期研究; 缺点为血清来源难以获得,患者存在异质性,模型结果评定以及实验标准化困难,同时血清中存在各种免疫蛋白及炎症介质,不能保证单因素影响 | 符合西医的有①、③、④、⑥,吻合度65%; 符合中医主症的有③、⑤; 符合中医次症的有⑤、⑥,总体吻合度40% |
利用杂交瘤细胞株制备单克隆抗体建立PTMG模型 Establishment of a PTMG model using hybridoma cell lines for the preparation of monoclonal antibodies | Lewis大鼠 | AChR单抗mAb35/mAbA7/mAbG10杂交瘤细胞株腹腔注射[ | 优点为建模时间短,发病率高,易于评估,适合进行短期研究 | 符合西医的有①、③、⑤,吻合度50%; 符合中医主症的有①、③、⑤,吻合度45% |
向实验动物脑室中注入MG患者AChR-Ab建立PTMG模型 Establishment of a PTMG model by injection of AChR-Ab from MG patients into the brain ventricles of experimental animals | SD大鼠 | 收集MG患者血清提取AChR-Ab,将其注入大鼠侧脑室,隔日重复,共3次。大约2周后建立CNS损害的大鼠模型[ | 优点为该模型的建立为阐明MG 中枢神经系统损害的机制提供依据; 缺点为操作复杂且难度高,同时对实验环境与条件要求严格 | 符合西医的有①、③、④、⑤,吻合度65%; 符合中医主症的有③; 符合中医次症的有⑥,总体吻合度20% |
通过MG患者胸腺组织移植建立PTMG模型 Establishment of a PTMG model by thymus tissue transplantation from MG patients | NOD/ SCID 小鼠 | 将 MG 患者的完整胸腺组织移植到严重联合免疫缺陷小鼠(NOD/SCID)小鼠肾被膜下[ | 优点为该方法为胸腺致敏机制打下基石; 缺点为胸腺细胞虽然参与了MG的发病过程,但不是MG唯一的致病因素 | 符合西医的有①、③、④、⑥,吻合度65%; 符合中医主症的有③; 符合中医次症的有⑥,总体吻合度20% |
通过移植MG患者外周淋巴细胞建立PTMG模型 Establishment of a PTMG model by transplantation of peripheral lymphocytes from MG patients | NOD/ SCID 小鼠 | 将MG患者血淋巴细胞进行腹腔注入NOD/SCID小鼠体内[ | 优点为CD4+T细胞在MG发病中的作用提供了依据 | 符合西医的有①、④、⑤,吻合度50%; 符合中医主症的有⑤; 符合中医次症的有⑥,总体吻合度20% |
MuSK诱导的EAMG模型 MuSK-induced EAMG model | C57BL/6J小鼠或Lewis大鼠 | 以大鼠MuSK基因编码序列为模板合成小鼠MuSK抗原,采取主动免疫法将小鼠MuSK与FCA混合制成抗原乳剂,通过尾静脉或腹腔注射入小鼠体内,28 d后重复注射一次[ | 缺点为MuSK抗体介导的MG的具体机制尚未完全明确,动物模型还处于研究阶段,且与AChR诱导的模型相比,发病率偏低且模型不成熟 | 符合西医的有①、③、④、⑤,吻合度65%; 符合中医主症的有①、③、⑤,总体吻合度45% |
重组人AChR建立EAMG模型 Recombinant human AChR modelling of EAMG | Lewis大鼠 | 将人工合成的人AChR α亚基1~210片段通过质粒转染的方法获得融合蛋白,并将其与等体积FCA制成乳剂,于大鼠肩背足垫等处多点注射[ | 优点为成模率高,免疫原充足,操作简便,成本低廉 | 符合西医的有①、③、⑤,吻合度50%; 符合中医主症的有①、③、⑤; 符合中医次症的有⑥,总体吻合度50% |
采用核酸疫苗建立EAMG模型 Modelling EAMG using nucleic acid vaccines | C57BL/6J小鼠[ | 核酸疫苗通过将克隆靶抗原编码的基因或DNA片段加入到如质粒、噬菌体等载体中去,然后向实验动物体内注入重组后的载体,而使得机体表达靶抗原基因,从而激活机体的免疫系统,产生相应的体液和细胞免疫。可以诱导小鼠的免疫系统识别并产生针对AChR的抗体,从而模拟MG的病理过程 | 优点为免疫原性好,可以产生较强的持久性免疫应答; 缺点为表现出的肌无力症状不严重,操作困难,同时该造模技术方法尚在探索和完善阶段 | 符合西医的有①、⑤,吻合度35%; 符合中医主症的有③,总体吻合度15% |
利用转基因小鼠神经肌肉接头局部产生的IFN-γ建立EAMG模型 Establishment of an EAMG model using locally produced IFN-γ in transgenic mice neuromuscular junction | BALB/c 小鼠 | 将鼠IFN-γ基因与调节性片段——鼠nAChRε基因融合,构建DNA质粒,植入小鼠卵母细胞,使新生小鼠在神经接头处表达该基因并产生IFN-γ[ | 优点为该模型为探索研究性模型,证明了MG的发病与IFN-γ有关,表现出的症状以及指标与人类MG相似度高; 缺点为典型性不足,操作复杂有难度 | 符合西医的有①、③、④、⑤,吻合度65%; 符合中医主症的有①、③、⑤; 符合中医次症的有⑤、⑥,总体吻合度55% |
利用人免疫球蛋白转基因小鼠构建EAMG模型 Construction of an EAMG model using human immunoglobulin transgenic mice | C57BL/6J小鼠 | 建立了表达人免疫球蛋白的转基因小鼠,并将由电鳐电器官提纯的AChR与FCA一起,于第0、3、5 周皮下注射该小鼠[ | 优点为该模型产生的抗体均为人源性抗体,在免疫学上更接近人MG; 缺点为成本高,操作难,模型尚未成熟 | 符合西医的有①、③、④、⑤,吻合度65%; 符合中医主症的有①、③、⑤; 符合中医次症的有⑤、⑥,总体吻合度55% |
LRP4诱导的EAMG模型 Model of LRP4-induced EAMG | C57BL/6小鼠 | 通过单体集聚蛋白与LRP4相互作用形成二元复合物,协同LRP4诱导的MG模型促进四聚体形成,从而影响运动神经元末梢释放集聚蛋白诱导的AChR聚集[ | 优点为该模型为研究探索性模型,为LRP4参与MG发病提供了依据; 缺点为成本高,模型稳定性不足 | 符合西医的有①、③、④,吻合度50%; 符合中医主症的有③,总体吻合度15% |
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