类风湿关节炎血瘀证大鼠模型的构建及评价
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1. 广州中医药大学第二临床医学院,广州 510006;2. 广东省中医院风湿科,广州 510000;3. 河南省洛阳正骨医院(河南省骨科医院),郑州 450016

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Establishment and evaluation of a rat model of blood stasis syndrome in rheumatoid arthritis
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1. the Second Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou 510000, China;2. Department of Rheumatology, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou 510006, China; 3. Luoyang Orthopedic Hospital of Henan Province(Henan Provincial Orthopedic Hospital), Zhengzhou 450016, China

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    摘要:

    目的 构建不同血瘀证型的胶原诱导性关节炎(collagen-induced arthritis,CIA)大鼠模型,并对不同造模方法进行评价,为建立稳定可靠的类风湿关节炎(rheumatoid arthritis,RA)血瘀证大鼠模型提供一定的依据。 方法 在 CIA 大鼠模型的基础上,分别叠加肾上腺素注射、冰水浴刺激、饥饿、脂多糖及高脂饲料喂养等多种因素,建立六种不同血瘀证模型。 采用关节肿胀度测量、AI 评分、Micro-CT、苏木素-伊红(HE)染色,同时检测血常规、血流动力学,并通过 ELISA 法检测炎症指标、凝血指标、血瘀相关指标等,对各造模方法进行综合评价。 结果 与空白组相比,单 CIA 组表现出炎症指标、血液学指标、血流动力学参数、凝血指标均明显升高,CT 显示骨破坏明显,HE 染色可见关节间隙面粗糙及炎性细胞浸润。 在此基础上,不同叠加刺激均加重血瘀证相关表现,但程度有所差异:CIA + Adr 组和 CIA + LPS 组表现为炎症、凝血及血管活性物质全面升高;CIA + Adr + 冰水浴组除炎症加重外,血流动力学指标出现部分下降;CIA + Adr + 冰水浴 + 饥饿组则在炎症和凝血指标异常的同时,部分因子降低;CIA + LPS + 高脂饲料组、CIA + 高脂饲料组则主要表现为血液学和血管内皮指标的异常。 结论 多种刺激因素可在 CIA 模型大鼠中成功诱导出不同血瘀证型,并呈现一定差异性。 本研究从多维度对 RA 血瘀证不同造模方式进行了全面评估,为进一步研究该疾病证型的发病机制和治疗策略提供了一定的实验依据。

    Abstract:

    Objective To construct collagen-induced arthritis ( CIA) rat models of different blood stasis syndrome types and evaluate various modeling method, thereby providing a basis for establishing stable and reliable rat models of blood stasis syndrome in rheumatoid arthritis (RA). Methods Based on the CIA rat model, six different blood stasis models were established by superimposing various factors including adrenaline injection, ice-water bath stimulation, starvation, lipopolysaccharide ( LPS) administration, and high-fat diet feeding. The modeling method were comprehensively evaluated by measuring joint swelling, arthritis index (AI) scoring, Micro-CT, hematoxylin and eosin (HE) staining, as well as assessing blood routine, hemodynamic parameters, and detecting inflammatory markers, coagulation indicators, and blood stasis-related indices via ELISA. Results Compared with the control group, the CIA-only group showed significantly increased inflammatory markers, hematological parameters,hemodynamic indices, and coagulation indicators. Micro-CT revealed significant bone destruction, and HE staining indicated rough articular surfaces and inflammatory cell infiltration. On this basis, different superimposed stimuli aggravated blood stasis-related manifestations to varying degrees: CIA + Adr group and CIA + LPS group exhibited comprehensive increases in inflammation, coagulation, and vasoactive substances. The CIA + Adr + ice water bath group showed worsened inflammation along with partial decreases in hemodynamic parameters. The CIA + Adr + ice water bath + starvation group demonstrated abnormalities in inflammatory and coagulation markers alongside reductions in certain factors. The CIA + LPS + high-fat diet group and CIA + high-fat diet group primarily exhibited abnormalities in hematological and vascular endothelial indicators. Conclusions Multiple stimuli can successfully induce different blood stasis syndrome types in CIA model rats, with certain differences observed. This study provides a comprehensive multidimensional evaluation of various modeling method for RA blood stasis syndrome, offering an experimental basis for further research into the pathogenesis and treatment strategies of this disease pattern.

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陈美琪,陈柏臻,马梦洋,杨璐,伍嘉琪,周颖燕,黄闰月,王茂杰,黄清春,何羿婷,何晓红.类风湿关节炎血瘀证大鼠模型的构建及评价[J].中国实验动物学报,2025,33(11):1559~1573.

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  • 收稿日期:2025-05-13
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  • 在线发布日期: 2026-01-08
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