中国组织工程研究

中国组织工程研究 ›› 2025, Vol. 29 ›› Issue (11): 2301-2309.doi: 10.12307/2025.353

• 组织构建实验造模 experimental modeling in tissue construction • 上一篇    下一篇

缺血性脑卒中痰热腑实证大鼠模型的建立与评价

平兴枫，吕军影，李  凯，黄宗轩，尹建新   

  1. 广西医科大学第一附属医院，广西壮族自治区南宁市  530021
  • 收稿日期:2024-03-09 接受日期:2024-05-11 出版日期:2025-04-18 发布日期:2024-08-12
  • 通讯作者: 吕军影，主任医师，教授，广西医科大学第一附属医院，广西壮族自治区南宁市 530021
  • 作者简介:平兴枫，男，1996年生，广西壮族自治区南宁市人，汉族，广西医科大学第一附属医院硕士，主要从事中西医结合临床内科疾病防治研究。
  • 基金资助:
    广西医疗卫生适宜技术开发与推广应用项目(S2018 050)，项目负责人：吕军影；广西中医药重点学科建设项目(GZXK-Z-20-52)，项目负责人：吕军影

Establishment and evaluation of a rat model of phlegm-heat and Fu-organ excess syndrome following ischemic stroke

Ping Xingfeng, Lyu Junying, Li kai, Huang Zongxuan, Yin Jianxin   

  1. First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
  • Received:2024-03-09 Accepted:2024-05-11 Online:2025-04-18 Published:2024-08-12
  • Contact: Lyu Junying, Chief physician, Professor, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
  • About author:Ping Xingfeng, Master, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
  • Supported by:
    Guangxi Medical and Healthcare Project for Appropriate Technology Development, Popularization and Application, No. S2018 050 (to LJY); Guangxi Traditional Chinese Medicine Key Discipline Construction Project, No. GZXK-Z-20-52 (to LJY)

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摘要：


文题释义：
病证结合动物模型：是在中医药理论指导下，在动物身上模拟出与人类疾病表现和证候特征相同或相似的实验动物模型。该模型以病为基础，以证为核心，提高了中医药实验结果的科学性与可靠性，是搭建传统医学与现代医学的桥梁，被多数中医药实验所采用，对推进中医药研究发展发挥重要作用。
线栓法：制备脑缺血大鼠模型方法包括光化学法、血栓法、线栓法，其中线栓法具有不开颅、损伤小、缺血部位固定等优点，应用广泛。线栓法的原理是将尼龙线自颈外动脉导入经颈内动脉的颅内段大脑中动脉起始处，阻断大脑中动脉血流，造成大脑中动脉供血区缺血。改良后直接将线栓由颈总动脉经颈内动脉直至大脑中动脉起始处，操作更为简单，成功率更高。

背景：中医药在治疗缺血性脑卒中痰热腑实证中具有丰富的经验和独特的优势，为深入挖掘中医药对该病的治疗靶点和治疗机制，建立稳定、可靠的缺血性脑卒中痰热腑实证病证结合动物模型是关键。
目的：探讨缺血性脑卒中痰热腑实证大鼠模型的建立方法及评价体系。
方法：采用随机数字表法将60只SD大鼠随机分为4组：空白对照组(n=12)、缺血性脑卒中组(n=18)给予普通饲料喂养25 d，病证结合组(n=18)、痰热腑实证组(n=12)给予高脂饲料喂养25 d；第26天，空白对照组、缺血性脑卒中组灌胃给予生理盐水，病证结合组、痰热腑实证组灌胃给予自体粪便混悬液，连续灌胃3 d(灌胃期间继续给予高脂饲料)；灌胃结束后，缺血性脑卒中组、病证结合组采用线栓法建立缺血性脑卒中模型，记录各组大鼠饮食量、饮水量、体质量、体温、粪便性状、鼻分泌物、喉中痰鸣、舌象等表征变化。造模结束后24 h，进行神经功能缺损评分、舌象表征、血脂水平检测、脑组织及颈动脉形态学观察以及血清胃动素和生长抑素水平检测。
结果与结论：①与空白对照组比较，病证结合组大鼠呼吸急促、精神萎靡、烦躁、行动迟缓，鼻周可见大量分泌物、可闻及厚重的喉中痰鸣，饮食量、饮水量下降，体质量、体温及舌下脉络评分升高，粪便粒数、Bristol评分及粪便含水率降低；血清总胆固醇、三酰甘油、低密度脂蛋白胆固醇及生长抑素水平升高，胃动素水平降低，神经功能缺损评分升高，颈动脉发生显著病理改变，脑组织显示明显缺血形态学改变。缺血性脑卒中组仅能造成缺血性脑组织病理改变，不能复制出痰热腑实证的证候特征。痰热腑实证组能复制出典型的中医证候特征，但不能构建出缺血性脑卒中的脑组织病理改变。②结果表明，高脂诱导结合线栓法及自体粪便灌胃的多因素复合造模方法，可建立缺血性脑卒中痰热腑实证病证结合动物模型。
https://orcid.org/0009-0002-0833-1368(平兴枫)

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

关键词: 缺血性脑卒中, 痰热腑实证, 病证结合, 动物模型, 症候因素

Abstract: BACKGROUND: Traditional Chinese medicine has rich experience and unique advantages in the empirical treatment of phlegm-heat and Fu-organs excess syndrome of ischemic stroke. In order to further explore the therapeutic targets and mechanisms of traditional Chinese medicine for this disease, it is crucial to establish a stable and reliable animal model of phlegm-heat and Fu-organs excess syndrome combined with empirical symptoms of ischemic stroke. 
OBJECTIVE: To explore the establishment method and evaluation system of the rat model of ischemic stroke with phlegm-heat and Fu-organ excess syndrome. 
METHODS: Sixty male Sprague-Dawley rats were randomly divided into four groups: blank control group (n=12), ischemic stroke group (n=18), disease+syndrome group (n=18), phlegm-heat and Fu-organ excess syndrome group (n=12), all of which were given high-fat diet for 25 days. On the 26th day, the rats in the blank control group and ischemic stroke group were intragastrically given normal saline and high fat diet, while those in the other two groups were intragastrically given autologous feces suspension and high fat diet for 3 continuous days. After gavage, ischemic stroke models were established using the suture method in the ischemic stroke group and disease+syndrome group. The changes in diet, water intake, body mass, body temperature, fecal traits, nasal secretions, sputum in the throat, and tongue image were recorded. Neurological deficits, tongue image, blood lipid levels, morphological changes of brain tissue and carotid artery, and the serum levels of motilin and somatostatin were detected. 
RESULTS AND CONCLUSION: Compared with the control group, the rats in the disease+syndrome group had shortness of breath, listlessness, irritability, bradykinesia, a large number of secretions around the nose, audible and heavy sputum in the throat, decreased diet and water intake, increased body mass, body temperature, and slingual vein score, decreased fecal pellet count, Bristol score and fecal moisture content, increased serum total cholesterol, triglyceride, low-density lipoprotein and somatostatin levels, decreased motilin level, increased neurological deficit score, significant pathological changes of the carotid artery, and significant morphological changes of the brain tissue. The ischemic stroke group only showed pathological changes of ischemic brain tissue, without the characteristics of phlegm-heat and Fu-organ excess syndrome. The phlegm-heat and Fu-organ excess syndrome group could present with the typical characteristics of traditional Chinese medicine syndromes, without the pathological changes of brain tissue with ischemic stroke. To conclude, the compound modeling method of high-fat induction combined with suture method and autologous feces gavage can establish an animal model of ischemic stroke with phlegm-heat and Fu-organ excess syndrome.

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

Key words: ischemic stroke, phlegm-heat and Fu-organ excess syndrome, combination of disease and syndrome, animal model, symptom factor

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