兔颈动脉狭窄模型的建立及其内膜切除治疗的实验研究
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摘要
目的：通过损伤颈动脉内皮细胞诱发动脉内膜增生，形成颈动脉狭
窄，建立颈动脉狭窄的动物模型；对其进行彩色多普勒（CDS）及动脉数字
减影血管造影（DSA）等影像学检查，了解其影像学改变特征；并采用内膜
切除法消除其狭窄，观察其对颈动脉狭窄的治疗效果。
方法与分组：
一、通过几种的不同方式损伤颈动脉内皮细胞：实验组A：10只动
物，单纯机械性损伤颈动脉内皮细胞（球囊剥脱）；实验组B：10只动物，
血流剪切应力对内皮的损伤（制造动脉外周狭窄增加血流切应力）；实验组
C：10只动物，机械性损伤与血流剪切力两者相结合的方式复制颈动脉
狭窄的动物模型；对照组D：10只动物，不损伤颈动脉内皮细胞。术后
2周后对所有存活动物抽血检查血脂浓度、并进行彩色多普勒和DSA检
查，然后从发生颈动脉狭窄者中选取2例，小心剥离出颈动脉，用10％
福尔马林溶液固定后行病理检查。
二、将其中经彩色多普勒检查证实狭窄程度在50％以上，并经DSA
检查证实有颈动脉狭窄者者共14例，在全麻下行颈动脉内膜切除术（CEA）
去除其狭窄，并于术后即刻、1月、2月、3月均行彩色多普勒检查。
结果：
一、各实验组与对照组的血脂浓度无明显差异。
二、彩色多普勒检查：（1）二维图像见内膜增厚、局部斑块和血管内
赘生物致血管腔狭窄；（2）彩色多普勒显示管腔内彩色血流束边缘不整齐
或局限性充盈缺损，伴有局部多彩镶嵌血流；（3）频谱多普勒显示狭窄处
及狭窄后管腔内峰值血流增快、频谱展宽且双峰间有明显切迹，舒张期
只有小量血流甚至无血流通过，阻力指数明显增大；（4）狭窄程度在50％
以上者共有14例（其中＾组7例、B组2例、C组5例）；因血栓形成或
血管钙化而完全闭塞者有6例（其中A组1例、B组1例、C组4例卜
三、动脉数字减影血管造影：血管造影可显示狭窄段颈动脉管壁高
低不平，呈向心性或偏心性狭窄，向心性狭窄表现为管径对称性缩窄，
而偏心性狭窄表现为充盈缺损：远端血管显影不良。
四、内膜切除术后各血管的狭窄程度较术前明显改善，但术后3月
再次复查时其中2例出现再狭窄。
结论：
一、单纯应用内皮损伤的方法即可复制兔颈动脉狭窄；
二、可应用B超及DSA对颈动脉的狭窄程度进行评估；
三、CEA可有效地消除颈动脉的狭窄，但术后可发生再狭窄。
Establishment of an Animal Model of Carotid Stenosis and
Experimental Studing of Cartoid Endarterectomy for Treating
the Stenosis
Department of Neurological Surgery. Wuhan General Hospital of PLA
Postgraduate: Zhang Xiaolun
Supervisor: Ma Lianting, Wu Zuoquan
Abstract
Objective: Establishment of an Animal Model of Carotid Stenosis by
endarterium hyperplasia caused by carotid endothelial cells injury; Assessing
the degree of carotid stenosis by colourful duplex sonography (CDS) and
selective carotid digital subtraction angiography(DSA) ;To determine the
curative effect of carotid endarterectomy on carotid stenosis in rabbits.
Methods and grouping:
1. The carotid endotbelial cells were injured by several ways: The
carotid endothelial cells were injured only by mechanical method in group A
Only by hemodynamical method in group B; By combination of mechanical
and hemodynamical method in group C; Do not injury endothelial cell in
control group D. CDS and slective DSA of the carotid artery were
performed; Cholesterol were examined two weeks after the injury in all
survival animals. The carotid arteries that become stenosal in two animals
were taken for histological examination.
2. That the degree of carotid stenosis was greater than 50 percent
(confirmed by CDS and DSA) in 14 rabbits, Who underwent carotid
endarterectomy to eliminate the stenosis, CDS was performed immediately
and one month, two months and three months following the operation.
Results:
-3-
1. There is no significant difference between the content of cholesterol
in all experimental groups and the control group
2. Colourful Duplex Sonography: (1) The carotid stenosis induced by
endoarterium hyperplasia and endovascular vegetation was revealed by two
dimensonal imaging; (2) Color doppler imaging reveal the endovascular
color blood stream was not smooth; (3) Frequency spectrum doppler imaging
reveal the peak velocity increase and resistance index augment. (4) In 14
rabbits the degrees of carotid stenosis were greater than 50 percent; In 6
animals the injured carotid arteries were occluded because of thrombosis or
calcifiation.
3. Carotid digital subtraction angiography: It was showed that vascular
walls were not smooth and vascular lemma became centripetally or
excentriclly stenotic; There was bad developing in the distal arteries.
4. The degree of carotid stenosis was apparently reduced after CEA, but
restenosis take placed in two cases 3 months later.
Conclusions:
1. Only injuring the carotid endothelial cells can replicate carotid
stenotic rabbits;
2. The carotid stenosis can be assessed by colourful duplex sonography
and selective carotid digital subtraction angiography;
3 .CEA can reduce carotid stenosis efficiently, but restenosis may take
place later.
窄，建立颈动脉狭窄的动物模型；对其进行彩色多普勒（CDS）及动脉数字
减影血管造影（DSA）等影像学检查，了解其影像学改变特征；并采用内膜
切除法消除其狭窄，观察其对颈动脉狭窄的治疗效果。
方法与分组：
一、通过几种的不同方式损伤颈动脉内皮细胞：实验组A：10只动
物，单纯机械性损伤颈动脉内皮细胞（球囊剥脱）；实验组B：10只动物，
血流剪切应力对内皮的损伤（制造动脉外周狭窄增加血流切应力）；实验组
C：10只动物，机械性损伤与血流剪切力两者相结合的方式复制颈动脉
狭窄的动物模型；对照组D：10只动物，不损伤颈动脉内皮细胞。术后
2周后对所有存活动物抽血检查血脂浓度、并进行彩色多普勒和DSA检
查，然后从发生颈动脉狭窄者中选取2例，小心剥离出颈动脉，用10％
福尔马林溶液固定后行病理检查。
二、将其中经彩色多普勒检查证实狭窄程度在50％以上，并经DSA
检查证实有颈动脉狭窄者者共14例，在全麻下行颈动脉内膜切除术（CEA）
去除其狭窄，并于术后即刻、1月、2月、3月均行彩色多普勒检查。
结果：
一、各实验组与对照组的血脂浓度无明显差异。
二、彩色多普勒检查：（1）二维图像见内膜增厚、局部斑块和血管内
赘生物致血管腔狭窄；（2）彩色多普勒显示管腔内彩色血流束边缘不整齐
或局限性充盈缺损，伴有局部多彩镶嵌血流；（3）频谱多普勒显示狭窄处
及狭窄后管腔内峰值血流增快、频谱展宽且双峰间有明显切迹，舒张期
只有小量血流甚至无血流通过，阻力指数明显增大；（4）狭窄程度在50％
以上者共有14例（其中＾组7例、B组2例、C组5例）；因血栓形成或
血管钙化而完全闭塞者有6例（其中A组1例、B组1例、C组4例卜
三、动脉数字减影血管造影：血管造影可显示狭窄段颈动脉管壁高
低不平，呈向心性或偏心性狭窄，向心性狭窄表现为管径对称性缩窄，
而偏心性狭窄表现为充盈缺损：远端血管显影不良。
四、内膜切除术后各血管的狭窄程度较术前明显改善，但术后3月
再次复查时其中2例出现再狭窄。
结论：
一、单纯应用内皮损伤的方法即可复制兔颈动脉狭窄；
二、可应用B超及DSA对颈动脉的狭窄程度进行评估；
三、CEA可有效地消除颈动脉的狭窄，但术后可发生再狭窄。
Establishment of an Animal Model of Carotid Stenosis and
Experimental Studing of Cartoid Endarterectomy for Treating
the Stenosis
Department of Neurological Surgery. Wuhan General Hospital of PLA
Postgraduate: Zhang Xiaolun
Supervisor: Ma Lianting, Wu Zuoquan
Abstract
Objective: Establishment of an Animal Model of Carotid Stenosis by
endarterium hyperplasia caused by carotid endothelial cells injury; Assessing
the degree of carotid stenosis by colourful duplex sonography (CDS) and
selective carotid digital subtraction angiography(DSA) ;To determine the
curative effect of carotid endarterectomy on carotid stenosis in rabbits.
Methods and grouping:
1. The carotid endotbelial cells were injured by several ways: The
carotid endothelial cells were injured only by mechanical method in group A
Only by hemodynamical method in group B; By combination of mechanical
and hemodynamical method in group C; Do not injury endothelial cell in
control group D. CDS and slective DSA of the carotid artery were
performed; Cholesterol were examined two weeks after the injury in all
survival animals. The carotid arteries that become stenosal in two animals
were taken for histological examination.
2. That the degree of carotid stenosis was greater than 50 percent
(confirmed by CDS and DSA) in 14 rabbits, Who underwent carotid
endarterectomy to eliminate the stenosis, CDS was performed immediately
and one month, two months and three months following the operation.
Results:
-3-
1. There is no significant difference between the content of cholesterol
in all experimental groups and the control group
2. Colourful Duplex Sonography: (1) The carotid stenosis induced by
endoarterium hyperplasia and endovascular vegetation was revealed by two
dimensonal imaging; (2) Color doppler imaging reveal the endovascular
color blood stream was not smooth; (3) Frequency spectrum doppler imaging
reveal the peak velocity increase and resistance index augment. (4) In 14
rabbits the degrees of carotid stenosis were greater than 50 percent; In 6
animals the injured carotid arteries were occluded because of thrombosis or
calcifiation.
3. Carotid digital subtraction angiography: It was showed that vascular
walls were not smooth and vascular lemma became centripetally or
excentriclly stenotic; There was bad developing in the distal arteries.
4. The degree of carotid stenosis was apparently reduced after CEA, but
restenosis take placed in two cases 3 months later.
Conclusions:
1. Only injuring the carotid endothelial cells can replicate carotid
stenotic rabbits;
2. The carotid stenosis can be assessed by colourful duplex sonography
and selective carotid digital subtraction angiography;
3 .CEA can reduce carotid stenosis efficiently, but restenosis may take
place later.
引文
1. Gorelich PB, et al. Stroke Prevention. Arch Neurol 1995; 52:347
2．黄友岐．神经病学第二版：人民教育出版社，1984．143
3. Easscott HHG, Pickering GW, et al. Reconstruction of internal carotid artery in a patient with intermittent attacks of hemiplegia. Lancet 1954; 2:994-6
4. Moore-WS; Barnett-HJ; Guidelines for carotid endarterectomy. A multidisciplinary consensus statement from the ad hoc Committee, American Heart Association. Stroke 1995 Jan; 26(1): 188-201
5．蔡海江．动脉粥样硬化基础与临床：江苏科学技术出版社，1996．38～87
6．孙宝贵．实验性家兔动脉粥样硬化狭窄模型．中国介入心脏病学杂志，1995，3：67～68
7. Srinivasan. Duplex Accuracy Compare With Angiography in the Veterans Affairs Cooperative Studies Trial for Symptomatic Carotid Stenosis. J Neuro Surgery 1995; 36:648-655
8. Mittl RL. Blinded Reader Comparison of Magnetic Resonance Angiography and Duplex Ultrasonography For Carotid Artery Bifurcation Stenosis. Stroke 1994;25:4-10
9. North American Symptomatic Carotid Endarterectomy Trial collaborators. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med 1991; 325:445-453
10．余建明．数字减影血管造影技术．第一版．北京：人民军医出版社，1995，371
11. Rothwell PM. Cerebrovascual Disease 1996; 6:54
12．来颖．实验性股动脉狭窄和成形术．白求恩医科大学学报，1995；21：41
13．姚谦．脑缺氧症的基础与临床．第一版．合肥：安徽科学出版社，1990．6～16
14. Constantinides P. The morphological basis for altered endothelial permeability in atherosclerosis. Advances in experimental medicine and biology, Vo182, Atherosclerosis.eds, Manning Gw and Haust MD, New York, Plenum Press,1977,969～1120
15. Flavahan NA. Atherosclerosis or lipoprotein-induced endothelial dysfunction, Circulation, 1992; 70:11
16. Moore S. Responses of the arterial wall to injury. Diabetes, 1981; 30:8
17. Masuda M, Motility patterns of cultured endothelial cells exposed to physiological level of fluid shear stress. Ann. N Y Acad Sci, 1990; 588:425
18. Levesque MJ.Correlation of endothelial cell shape and wall shear stress in a stenosed dog aorta. Arteriosclerosis, 1986; 6:220
19. Salonen JP. Ultrasonographically assessed carotid atherosis and the risk of acute myocardial infarction. Circulation. 1991; 83:23
20. Craven TE.Evaluation of the associations between carotid artery atherosclerosis and cororary artery stenosis. Circulation. 1990; 82:1320
21. Howard G A multicentervalidation study of Doppler ultrasound versus angiography.J Stroke Cerobrovasc Dis, 1991; 1:166
22. Executive Committee For Asymptomatic Carotid Atherosclerosis Study: Endarterectomy for Asymptomatic Carotid Artery Stenosis. JAMA 1995; 273:1421-1428
23. Fields WS, Maslenikov V. et al. Joint study of extracranial arterial occlusion. Progress report of prognosis following surgery or nonsurgical treatment for transient cerebral ischemic attacks and cervical carotid artery lesions. JAMA 1970; 211:1993-2003
24. Shaw DA, Venables GS, et al. Carotid endarterectomy in patients with transient cerebral ischaemia. J Neurol Sci 1984; 64:45-53.
25. European Carotid Surgery Trialists'Group: MRC European Carotid Surgery Trial: interim results for symptomatic patients with severe (70-99%) or (0-29%) carotid stenosis. Lancet 1991; 337:1235o-43
26．曹贵松．颈动脉狭窄的外科治疗．第二军医大学学报．1999；20：917
27．周定标．颈动脉内膜切除治疗颈动脉狭窄．中华医学杂志．1999；79：816～818
28．丁家增．76例颈动脉内膜剥脱术并发症分析．上海第二医科大学学报．1999；19：458
29. Mullan S, Duda E. Some examples of balloon technology in neurosurgery. J
Neurosurg 1980; 52:321-329
30． Kerber CW, Cromwell LD, Loehden OL.Catheter dilatation of proximal stenosis during distal bifurcation endarterectomy. AJNR 1980; 1:348-349
31． Higashida R, et al. Cerebral Percutaneous Angioplasty. Heart Disease and stoke 1993; 2:497-502
32． Brown M. Balloon angioplasty for cerebrovascular disease. Neurol Res 1992; 14(suppl to No.2) : 159-163
33． Munari L, Belloni G, et al. Carotid percutaneous angioplasty. Neurol Res 1992; 14(suppl to No.2) : 156-158
34． Fishman DL, Leon MB, et al. For the stent restenosis study investigators. A randomized comparison if coronary stent placement and balloon angioplasty in the treatment of coronary artery disease. N Engl J Med 1994; 331:496-501
35． Serruys PW, de Jaegere P, et al. For the stent restenosis study investigators. A randomized comparison if coronary stent placement and balloon angioplasty in the treatment of coronary artery disease. N Engl J Med 1994; 331:489-495
36． Dotter CT. Transluminally placed string coils and arterial tube grafts: long-term Patency in the canine popliteal. Invest Radiol 1969; 4:329-305
37． Yadav JS, Roubin GS, et al. Elective stenting of the extracranial carotid arteries. Circulation 1997; 95:376-381
2．黄友岐．神经病学第二版：人民教育出版社，1984．143
3. Easscott HHG, Pickering GW, et al. Reconstruction of internal carotid artery in a patient with intermittent attacks of hemiplegia. Lancet 1954; 2:994-6
4. Moore-WS; Barnett-HJ; Guidelines for carotid endarterectomy. A multidisciplinary consensus statement from the ad hoc Committee, American Heart Association. Stroke 1995 Jan; 26(1): 188-201
5．蔡海江．动脉粥样硬化基础与临床：江苏科学技术出版社，1996．38～87
6．孙宝贵．实验性家兔动脉粥样硬化狭窄模型．中国介入心脏病学杂志，1995，3：67～68
7. Srinivasan. Duplex Accuracy Compare With Angiography in the Veterans Affairs Cooperative Studies Trial for Symptomatic Carotid Stenosis. J Neuro Surgery 1995; 36:648-655
8. Mittl RL. Blinded Reader Comparison of Magnetic Resonance Angiography and Duplex Ultrasonography For Carotid Artery Bifurcation Stenosis. Stroke 1994;25:4-10
9. North American Symptomatic Carotid Endarterectomy Trial collaborators. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med 1991; 325:445-453
10．余建明．数字减影血管造影技术．第一版．北京：人民军医出版社，1995，371
11. Rothwell PM. Cerebrovascual Disease 1996; 6:54
12．来颖．实验性股动脉狭窄和成形术．白求恩医科大学学报，1995；21：41
13．姚谦．脑缺氧症的基础与临床．第一版．合肥：安徽科学出版社，1990．6～16
14. Constantinides P. The morphological basis for altered endothelial permeability in atherosclerosis. Advances in experimental medicine and biology, Vo182, Atherosclerosis.eds, Manning Gw and Haust MD, New York, Plenum Press,1977,969～1120
15. Flavahan NA. Atherosclerosis or lipoprotein-induced endothelial dysfunction, Circulation, 1992; 70:11
16. Moore S. Responses of the arterial wall to injury. Diabetes, 1981; 30:8
17. Masuda M, Motility patterns of cultured endothelial cells exposed to physiological level of fluid shear stress. Ann. N Y Acad Sci, 1990; 588:425
18. Levesque MJ.Correlation of endothelial cell shape and wall shear stress in a stenosed dog aorta. Arteriosclerosis, 1986; 6:220
19. Salonen JP. Ultrasonographically assessed carotid atherosis and the risk of acute myocardial infarction. Circulation. 1991; 83:23
20. Craven TE.Evaluation of the associations between carotid artery atherosclerosis and cororary artery stenosis. Circulation. 1990; 82:1320
21. Howard G A multicentervalidation study of Doppler ultrasound versus angiography.J Stroke Cerobrovasc Dis, 1991; 1:166
22. Executive Committee For Asymptomatic Carotid Atherosclerosis Study: Endarterectomy for Asymptomatic Carotid Artery Stenosis. JAMA 1995; 273:1421-1428
23. Fields WS, Maslenikov V. et al. Joint study of extracranial arterial occlusion. Progress report of prognosis following surgery or nonsurgical treatment for transient cerebral ischemic attacks and cervical carotid artery lesions. JAMA 1970; 211:1993-2003
24. Shaw DA, Venables GS, et al. Carotid endarterectomy in patients with transient cerebral ischaemia. J Neurol Sci 1984; 64:45-53.
25. European Carotid Surgery Trialists'Group: MRC European Carotid Surgery Trial: interim results for symptomatic patients with severe (70-99%) or (0-29%) carotid stenosis. Lancet 1991; 337:1235o-43
26．曹贵松．颈动脉狭窄的外科治疗．第二军医大学学报．1999；20：917
27．周定标．颈动脉内膜切除治疗颈动脉狭窄．中华医学杂志．1999；79：816～818
28．丁家增．76例颈动脉内膜剥脱术并发症分析．上海第二医科大学学报．1999；19：458
29. Mullan S, Duda E. Some examples of balloon technology in neurosurgery. J
Neurosurg 1980; 52:321-329
30． Kerber CW, Cromwell LD, Loehden OL.Catheter dilatation of proximal stenosis during distal bifurcation endarterectomy. AJNR 1980; 1:348-349
31． Higashida R, et al. Cerebral Percutaneous Angioplasty. Heart Disease and stoke 1993; 2:497-502
32． Brown M. Balloon angioplasty for cerebrovascular disease. Neurol Res 1992; 14(suppl to No.2) : 159-163
33． Munari L, Belloni G, et al. Carotid percutaneous angioplasty. Neurol Res 1992; 14(suppl to No.2) : 156-158
34． Fishman DL, Leon MB, et al. For the stent restenosis study investigators. A randomized comparison if coronary stent placement and balloon angioplasty in the treatment of coronary artery disease. N Engl J Med 1994; 331:496-501
35． Serruys PW, de Jaegere P, et al. For the stent restenosis study investigators. A randomized comparison if coronary stent placement and balloon angioplasty in the treatment of coronary artery disease. N Engl J Med 1994; 331:489-495
36． Dotter CT. Transluminally placed string coils and arterial tube grafts: long-term Patency in the canine popliteal. Invest Radiol 1969; 4:329-305
37． Yadav JS, Roubin GS, et al. Elective stenting of the extracranial carotid arteries. Circulation 1997; 95:376-381
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