CaCl2联合FeCl3诱导猪股动脉慢性完全闭塞样病变模型的构建与初步验证
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复旦大学附属华东医院 血管外科,上海 200040

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周可倩,复旦大学附属华东医院硕士研究生,主要从事外周动脉疾病、下肢动脉慢性闭塞模型及血管介入转化方面的研究。

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上海市科技创新行动计划基金资助项目(22Y11909500);上海市科技产业高质量发展计划“创新药械产品应用示范”基金资助项目(25SF1909005)。


Establishment and preliminary validation of a porcine femoral artery chronic total occlusion-like lesion model induced by combined CaCl2 and FeCl3 treatment
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Department of Vascular Surgery, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China

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    摘要:

    背景与目的 外周动脉疾病(PAD)中的慢性完全闭塞(CTO)病变常伴血栓形成、血管重构及钙化等复杂病理改变,现有动物模型难以同时模拟上述特征。本研究探索采用氯化钙(CaCl2)联合三氯化铁(FeCl3)局部处理构建猪股动脉CTO样病变模型的可行性。方法 选取1头健康成年白猪,对右侧股动脉进行CaCl2灌注、FeCl3滤纸贴敷及血管外膜周围CaCl?局部注射处理,对侧股动脉作为假手术对照。分别于术前、术后2个月及术后3个月采用数字减影血管造影(DSA)和CT血管造影(CTA)进行影像学评估,并于术后3个月取材行HE染色观察组织学改变。结果 DSA显示建模侧股动脉于术后2个月和术后3个月均持续闭塞,术后3个月延迟相可见细小连续侧支形成。CTA显示建模段重度狭窄或闭塞,伴管腔充盈缺损及管壁局灶性高密度影。HE染色显示病变段存在血栓形成及机化、内膜增厚和结构破坏、中膜平滑肌排列紊乱,并可见局灶性可疑钙盐沉积样改变。结论 本单例初步可行性研究表明,CaCl2联合FeCl3局部处理可在猪股动脉诱导形成以持续性管腔闭塞和血栓机化为主要特征,并伴局灶性钙盐沉积样改变的CTO样病变。该方法可为大动物下肢动脉慢性闭塞模型的构建提供探索性方案,其稳定性和可重复性仍需进一步研究验证。

    Abstract:

    Background and Aims Chronic total occlusion (CTO) lesions in peripheral artery disease (PAD) are characterized by complex pathological changes including thrombosis, vascular remodeling, and calcification. Existing animal models are often unable to simultaneously reproduce these features. This study explored the feasibility of establishing a porcine femoral artery CTO-like lesion model using combined focal treatment with calcium chloride (CaCl2) and ferric chloride (FeCl3).Methods One healthy adult white pig was used. The right femoral artery underwent intraluminal CaCl2 perfusion, FeCl3-soaked filter paper application, and additional perivascular CaCl2 injection, while the contralateral femoral artery served as a sham-operated control. Digital subtraction angiography (DSA) and computed tomography angiography (CTA) were performed before modeling and at 2 and 3 months after modeling. Histological changes were evaluated by hematoxylin-eosin (HE) staining at 3 months.Results DSA demonstrated persistent occlusion of the modeled femoral arterial segment at both 2 and 3 months, with small continuous collateral vessels observed in the delayed phase at 3 months. CTA showed severe stenosis or occlusion of the modeled segment, accompanied by intraluminal filling defects and focal high-density shadows on the vessel wall. HE staining revealed thrombus formation and organization, intimal thickening and disruption, disordered arrangement of medial smooth muscle cells, and focal suspected calcium salt deposition-like changes.Conclusion This single-case preliminary feasibility study suggests that combined focal treatment with CaCl2 and FeCl3 can induce a CTO-like lesion in the porcine femoral artery, characterized by persistent luminal occlusion and thrombus organization with focal calcium salt deposition-like changes. This method may provide an exploratory approach for constructing large-animal models of lower-limb arterial chronic occlusion, although its reproducibility and stability require further validation.

    图1 猪股动脉慢性闭塞建模流程示意图Fig.1 Schematic diagram of the establishment procedure for the porcine femoral artery chronic occlusion lesion model
    图2 DSA观察猪股动脉建模前后管腔通畅性及侧支循环变化(粗箭头示建模段闭塞区域,细箭头示侧支血管) A:建模前右侧股动脉管腔通畅,远端显影良好;B:术后2个月时,建模段股动脉未显影,远端显影减弱;C:术后3个月时,建模段持续闭塞,延迟相可见细小连续侧支通路形成Fig.2 DSA observation of femoral artery patency and collateral formation before and after modeling (thick arrows indicate the occlusive segment, and thin arrows indicate collateral vessels) A: Patent femoral artery before modeling with good distal opacification; B: Occlusion of the modeled segment at 2 months with reduced distal filling; C: Persistent occlusion at 3 months with small continuous collateral vessels visible in the delayed phase
    图3 CTA及三维重建观察猪股动脉建模后血管形态改变(红色实心箭头示建模手术侧股动脉闭塞区域,红色空心箭头示对侧假手术侧股动脉,蓝箭头示局灶性高密度影) A:术后2个月CTA图像,可见建模段股动脉闭塞,并伴局灶性高密度影;B:术后3个月CTA图像,可见建模段股动脉持续闭塞,并伴局灶性高密度影;C:术后2个月三维重建图像,可见建模段管腔闭塞及局灶性高密度影;D:术后3个月三维重建图像,可见闭塞段持续存在,远端股动脉主干显影Fig.3 CTA and three-dimensional reconstruction showing vascular morphological changes after modeling (solid red arrows indicate the occlusive segment of the modeled operated femoral artery, hollow red arrows indicate the contralateral sham-operated femoral artery, and blue arrows indicate focal high-density shadows) A: CTA at 2 months showing occlusion of the modeled femoral arterial segment with focal high-density shadows; B: CTA at 3 months showing persistent occlusion with focal high-density shadows; C: Three-dimensional reconstruction at 2 months showing luminal occlusion and focal high-density shadows; D: Three-dimensional reconstruction at 3 months showing persistent occlusion and distal femoral artery opacification.
    图4 HE染色观察猪股动脉建模后组织学改变(比例尺:312.5 μm) A:假手术侧股动脉,管腔通畅,管壁结构完整、层次清晰;B:建模侧股动脉,管腔内可见血栓形成/机化,伴内膜结构破坏及局灶性可疑钙盐沉积样改变Fig.4 HE staining showing histological changes after femoral artery modeling (scale bar=312.5 μm) A: Sham-operated femoral artery showing a patent lumen and intact layered vessel wall structure; B: Modeled femoral artery showing intraluminal thrombus formation/organization, intimal disruption, and focal suspected calcium salt deposition-like changes
    图1 猪股动脉慢性闭塞建模流程示意图Fig.1 Schematic diagram of the establishment procedure for the porcine femoral artery chronic occlusion lesion model
    图2 DSA观察猪股动脉建模前后管腔通畅性及侧支循环变化(粗箭头示建模段闭塞区域,细箭头示侧支血管) A:建模前右侧股动脉管腔通畅,远端显影良好;B:术后2个月时,建模段股动脉未显影,远端显影减弱;C:术后3个月时,建模段持续闭塞,延迟相可见细小连续侧支通路形成Fig.2 DSA observation of femoral artery patency and collateral formation before and after modeling (thick arrows indicate the occlusive segment, and thin arrows indicate collateral vessels) A: Patent femoral artery before modeling with good distal opacification; B: Occlusion of the modeled segment at 2 months with reduced distal filling; C: Persistent occlusion at 3 months with small continuous collateral vessels visible in the delayed phase
    图3 CTA及三维重建观察猪股动脉建模后血管形态改变(红色实心箭头示建模手术侧股动脉闭塞区域,红色空心箭头示对侧假手术侧股动脉,蓝箭头示局灶性高密度影) A:术后2个月CTA图像,可见建模段股动脉闭塞,并伴局灶性高密度影;B:术后3个月CTA图像,可见建模段股动脉持续闭塞,并伴局灶性高密度影;C:术后2个月三维重建图像,可见建模段管腔闭塞及局灶性高密度影;D:术后3个月三维重建图像,可见闭塞段持续存在,远端股动脉主干显影Fig.3 CTA and three-dimensional reconstruction showing vascular morphological changes after modeling (solid red arrows indicate the occlusive segment of the modeled operated femoral artery, hollow red arrows indicate the contralateral sham-operated femoral artery, and blue arrows indicate focal high-density shadows) A: CTA at 2 months showing occlusion of the modeled femoral arterial segment with focal high-density shadows; B: CTA at 3 months showing persistent occlusion with focal high-density shadows; C: Three-dimensional reconstruction at 2 months showing luminal occlusion and focal high-density shadows; D: Three-dimensional reconstruction at 3 months showing persistent occlusion and distal femoral artery opacification.
    图4 HE染色观察猪股动脉建模后组织学改变(比例尺:312.5 μm) A:假手术侧股动脉,管腔通畅,管壁结构完整、层次清晰;B:建模侧股动脉,管腔内可见血栓形成/机化,伴内膜结构破坏及局灶性可疑钙盐沉积样改变Fig.4 HE staining showing histological changes after femoral artery modeling (scale bar=312.5 μm) A: Sham-operated femoral artery showing a patent lumen and intact layered vessel wall structure; B: Modeled femoral artery showing intraluminal thrombus formation/organization, intimal disruption, and focal suspected calcium salt deposition-like changes
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周可倩,杜莎,张金明,马乾超,竺挺,张婉. CaCl2联合FeCl3诱导猪股动脉慢性完全闭塞样病变模型的构建与初步验证[J].中国普通外科杂志,2026,35(6):1199-1205.
DOI:10.7659/j. issn.1005-6947.260005

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  • 收稿日期:2026-01-04
  • 最后修改日期:2026-06-02
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  • 在线发布日期: 2026-07-30
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