小型猪脑卒中模型构建的可行性研究
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1.云南农业大学 云南省小型猪基因编辑与异种器官移植重点实验室;2.云南农业大学动物医学院;3.福建医科大学附属第二医院;4.云南农业大学食品科学技术学院;5.云南农业大学动物科学技术学院;6..云南农业大学动物医学院

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云南省重大科技专项计划(202102AA100054)


Feasibility Study on the Construction of a Small Porcine Stroke Model
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1.Yunnan Provincial Key Laboratory of Gene Editing and Xenotransplantation of Small Pigs,Yunnan Agricultural University;2.China;3.College of Veterinary Medicine,Yunnan Agricultural University;4.2nd Affiliated Hospital of Fujian Medical University;5.College of Food Science and Technology, Yunnan Agricultural University;6.College of Animal Science and Technology, Yunnan Agricultural University;7.2nd Affiliated Hospital of Fujian Medical University, Quanzhou 362000, China;8.Yunnan Provincial Key Laboratory of Gene Editing and Xenotransplantation of Small Pigs, Yunnan Agricultural University, Kunming 650201, China;9.College of Veterinary Medicine, Yunnan Agricultural University, Kunming 650201, China College of Animal Science and Technology, Yunnan Agricultural University, Kunming 650201, China

Fund Project:

Yunnan Province Major Science and Technology Special Programme (202102AA100054).

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    摘要:

    目的 本研究旨在构建具有高度临床相关性的缺血性脑卒中和出血性脑卒中小型猪模型,通过监测两种脑卒中术后疾病发生发展的病理生理过程,评估小型猪作为脑卒中体内模型构建的可行性,为脑卒中机制研究和治疗策略开发提供更精确的实验工具。方法 通过注入自体血(两次注血法)和开颅血管电凝法分别构建HS模型和IS模型,术后对模型猪进行行为学评估、生理生化指标检测及脑组织病理学分析和神经细胞标志物免疫组化验证,全面评估模型与临床脑卒中发生发展过程的相似性。结果 IS模型猪表现出严重的偏瘫、运动障碍及意识反应减退,脑组织缺血坏死明显,炎症反应剧烈,神经元凋亡显著,肝肾功能轻度受损;HS模型猪出现轻度行为障碍,血肿形成稳定,伴有脑水肿和机械性压迫,炎症反应活跃,神经元损伤及胶质细胞活化明显。两种模型均表现出良好的稳定性和重复性。结论 本研究成功构建了具有高度临床相关性的IS和HS小型猪模型,验证了小型猪构建脑卒中模型的可行性与准确性,为针对性治疗策略的开发提供了实验基础具备较高的临床相关性和实验价值,有助于促进脑卒中精准治疗的发展。

    Abstract:

    Objective The aim of this study was to construct minipig models of ischaemic stroke and haemorrhagic stroke with high clinical relevance, to assess the feasibility of minipigs as in vivo models of stroke by monitoring the pathophysiological processes of the disease development after two types of strokes, and to provide a more accurate experimental tool for the study of stroke mechanisms and the development of therapeutic strategies.Methods The HS model and IS model were constructed by injecting autologous blood (twice injection method) and cranial vascular electrocoagulation, respectively. Behavioural assessment, physiological and biochemical indexes, and histopathological analysis of brain tissue, as well as immunohistochemical verification of neuronal markers were carried out in the model pigs after surgery to comprehensively assess the similarity between the models and the clinical stroke development process.Results IS model pigs showed severe hemiparesis, motor disorders and reduced conscious response, obvious ischemic necrosis of brain tissues, intense inflammatory response, significant neuronal apoptosis, and mild impairment of liver and kidney functions; HS model pigs showed mild behavioural disorders, stable haematoma formation, accompanied by cerebral oedema and mechanical compression, active inflammatory response, and obvious neuronal damage and glial cell activation.Both models showed good stability and reproducibility.Conclusion In this study, we successfully constructed IS and HS minipig models with high clinical relevance, verified the feasibility and accuracy of constructing stroke models in minipigs, and provided an experimental basis for the development of targeted therapeutic strategies with high clinical relevance and experimental value, which can help to promote the development of precision stroke therapy.

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  • 收稿日期:2025-06-09
  • 最后修改日期:2025-12-17
  • 录用日期:2026-01-14
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