低频高能超声血管成形术的基础与临床研究
|
摘要
超声血管成形术是近年来引起国内外学者关注的一种新的血运重建方
式，采用低频高能超声的机械振动、空化作用等效应裂解粥样硬化斑块、
消融血栓、恢复闭塞血管的再通，而对正常血管壁各层结构几乎无损伤。
本研究的目的在于：①.通过对低频高能超声作用后动物模型血管平滑肌
细胞（VSMC）C-sis表达水平、血小板衍生生长因子（PDGF）、细胞增
生状态的评价，明确低频高能超声对平滑肌细胞增殖效应的影响；②应
用低频高能超声消融体外全血细胞血栓及体内急性心肌梗塞死、陈旧性心
肌梗死患者，观察超声消融血栓的效果、安全性；③体内超声消融冠脉重
度狭窄，研究低频高能超声对粥样硬化斑块消融的效果。
本研究实验兔分为正常对照组、试验对照组、球囊损伤组、超声消融
组。后二组分别在颈动脉损伤后48h、72h、96h、120h、1w、2w，取目
标段动脉约4cm，分成4份，长度各约1cm。制备后采用RT-PCR法测定
C-sis mRNA表达、~3H-TdR掺入法测定SMC DNA合成含量、免疫组织化
学染色法计算PDGF β-阳性指数、PCNA阳性指数。观察球囊损伤、低
频高强度超声对平滑肌细胞增殖效应的影响。结果发现，超声消融组、正
常对照组与试验对照组VSMC的C-sis表达、PDGF-βmRNA含量、PCNA
染色及~3H-TdR掺透量均无显著增加；而球囊损伤的兔VSMC各时相点均
有C-sis表达，其高峰期出现在球囊损伤1周，表达量增高了6.5倍。48h
开始出现PDGF、PCNA阳性VSMC细胞，1周时相点达到峰值。72h开
始氚掺透值持续升高，至1周达高峰。
采集正常人静脉血2ml制备为全血细胞凝块20例并行重量测定。应
用40KHz，18W/cm~2脉冲式超声对全血细胞凝块消融。消融后取沉淀涂
片，显微镜下检查碎块大小，并与红细胞直径比较。结果发现，超声能量
释放15秒内血栓完全溶解，溶解速度为0二兆土0刀N七。显微镜下检查
90％的碎片直径小于红细胞直径。
应用低频高能超声通过导管技术对急性心肌梗死、陈旧性心肌梗死
及其PTCA失败的患者进行消融，观察消融前后闭塞相关血管（IRA）TIMI
血流改变并利用 SHIMADZU Dghtex a 2400计算机分析系统测量残余狭
窄程度，检测手术前后CK－MB、心电图ST段及临床症状的改变，评价
低频高能超声血管成形术治疗心肌梗死的可行性。测定消融前后静脉血中
PL＊P＊T、卜PA、PA 的含量及观察超声消融中有无冠状动脉痉挛。撕
裂等影像学改变。结果发现，10例 AMI患者中消融后 9例 IRA达到 TIMI
血流3级，开通率为90％（9／10）。10分钟后9例患者胸痛消失、ST段
下降）50％，CK－MB峰值明显前移（5石士1．二小时）。2例患者超声消融
后冠状动脉造影闭塞相关血管管腔大于非狭窄段，30分钟后造影残余狭
窄分别为 24o、180。8例 OMI患者中，7例消融后 IRA达 TIMI血流 3
级，开通率为87．5％（／8），30分钟后造影闭塞相关血管TIMI仍为3
级。术后30分钟缺血性盯段下移明显好转（上移350o）。5例常规PTCA
失败患者经超声消融，IRA均达 TIMI3级，残余狭窄为 64石土 12石4％。
低频高能超声通过导管技术对冠脉重度狭窄进行消融，比较消融前
后冠脉狭窄程度的改变，分析手术前后常规心电图ST段改变，手术前后
运动试验测定诱发心绞痛所需时间、运动诱发 ST段下降 0．lmV所需时间、
运动诱发ST段下降最大幅度的比较。结果发现，15支狭窄口75％的血管
消融后残余狭窄为 43．03 i 15．49o，较术前降低 42．030（43．03士
15．49％VS85．83土5．44％，p＜0．05），5例消融后残余狭窄＜30％ （3．33％，
5／15）。术后心电图缺血性ST段压低较术前明显好转。术后运动诱发心绞
痛所需时间及运动诱发 ST段下降 0．lmV所需时间、运动诱发 ST段下降
最大幅度与手术前比较均有显著差异（P＜0．01）。
本研究结论：1．低频高能超声作用后VSMC的增生、迁移无显著改
变。2．体外实验及临床病例研究证实低频高能超声能有效溶解新鲜及陈旧
性血栓，无血管损伤、微栓塞等严重并发症，对凝血、纤溶系统无不良影
Vll
￡
响。3．低频高能超声血管成形术治疗AMI、OMI，可使IRA早期再通，
恢复TIMI级血流，是一种新的冠脉血运重建方式。4．血管闭塞时间长，
常规PTCA失败的病例，超声血管成形术能成功再通闭塞血管，提高PTCA
的成功率。5．超声能量可以有效裂解粥样硬化斑块，但仍然存在血管残余
狭窄；与球囊扩张联合应用能够降低所需压力，改善术后再狭窄。6．低频
高能超声的血管舒张作用，提高了超声血管成形术的可操作性及安全性。
An experimental and clinical study on angioplasty with lowfrequency and high-energy ultrasounds
Ultrasonic angioplasty, as a new approach for reconstruction of blood supply, has attracted attention from researchers at home and abroad in recent years. For this technique, such effects as mechanical vibration and cavitation etc. exerted by low frequency and high-energy ultrasounds (LFHEU) are employed to restore potency of blood vessels by splitting atherosclerotic plaques and dissolving thrombi. Meanwhile, the technique does not damage normal vascular structure. This study was designed to investigate angioplasty with LFHEU. The purposes and brief procedures are as follows: 1) After vascular smooth muscle cells (VSMC) in an animal model were treated with LFHEU, expression of C-sis and platelet-derived growth factor (PDGF) and proliferation state of the cells were evaluated to determine effects of LFHEU on proliferation of smooth muscle cells. 2) LFHEU was used to dissolve panhematic thrombi formed in vitro and those in patients with acute myocardial infarction or old myocardial infarction to determine its safety and efficiency in dissolving thrombi. 3) LFHEU was used to treat serious stenosis of the coronary artery to investigate its dissolving effects on atherosclerotic plaques.
In this study, rabbits were randomized into normal control group (group A), experimental control group (group B), balloon-injured group (group C) and ultrasonic dissolved group (group D). After the injury in carotid artery, the target segment of the common carotid artery with a length of 4 cm in rabbits in the latter two groups was extracted at 48, 72, 96, 120 hours and 1 and 2 weeks, respectively. The segment was divided into 4 parts with a length of approximately 1 cm in each. Expression of C-sis mRNA was determined by RT-PCR, synthesis and content of DNA in smooth muscle cells measured by 3H-TdR incorporation and positive indexes of PDGF-~ and PCNA by PDGF-~
and PCNA immunohistochemical staining to determine effects of balloon
injury and LFHEU on proliferation of smooth mu5cle cel1s. It was fOund that
there were no expression of C-sis and significant increase in the conteflt of
PDGF-0, PCNA staining and incorporation of 3H-TdR in Group A, Group B
and Group D. In Group C, typical expression of C-sis of cytokines encoding
PDGF-0 appeared and its peak was found in l week after the injury. The
expression intensity was increased for 6.5 times. PDGF-positive smooth
muscle ce1ls began to aPpear at 48 hours and the number reached its peak at 1
week after the injury. Incorporation value of tritium began to be continuously
elevated in 72 hours and reached its peak at 1 week after the injury.
Venous blood of 2 ml was collected from volunteers to prepare 20
panhematic c1ots. Then the colt was weighed. Ultrasounds of 40 KHz and l8
Wcm2 was used to dissolve the clots till its disaPpearance. After the dissolved
substance was made stationary, the supernatant was discarded and sediment
col1ected for smear examination under the microscope. Microscopic
examination revealed that the diameter of 90% of pieces produced in dissolve
was smaller than that of red blood cells and prepared panhematic clots were
completely dissolved in l5 seconds (dissolving speed = 0. 13 8 i 0.018g/s).
LFHEU was introduced via catheterization to treat patients with acute
myocardial infarction, old myocardial infarction and those with old myocardial
infarction in whom PTCA failed. Degree of residual stenosis was measured and
analyzed with SHIMADZU Digitex a 2400 computerized analyzing system and
changes in blood flow in infarction-related arteries (IRA), CK-MB after the
treatment, ST segmeni in ECG and clinical manifestations were observed to
evaluate feasibility of using angioplasty with LFHEU to treat myocardial
infarction. Safety of ultrasonic angioplasty was exp1ored by measuring contents
of PT, APTT t-PA and PAI in venous blood before and after the treatment to
determine whether there were imaging changes such as coron
式，采用低频高能超声的机械振动、空化作用等效应裂解粥样硬化斑块、
消融血栓、恢复闭塞血管的再通，而对正常血管壁各层结构几乎无损伤。
本研究的目的在于：①.通过对低频高能超声作用后动物模型血管平滑肌
细胞（VSMC）C-sis表达水平、血小板衍生生长因子（PDGF）、细胞增
生状态的评价，明确低频高能超声对平滑肌细胞增殖效应的影响；②应
用低频高能超声消融体外全血细胞血栓及体内急性心肌梗塞死、陈旧性心
肌梗死患者，观察超声消融血栓的效果、安全性；③体内超声消融冠脉重
度狭窄，研究低频高能超声对粥样硬化斑块消融的效果。
本研究实验兔分为正常对照组、试验对照组、球囊损伤组、超声消融
组。后二组分别在颈动脉损伤后48h、72h、96h、120h、1w、2w，取目
标段动脉约4cm，分成4份，长度各约1cm。制备后采用RT-PCR法测定
C-sis mRNA表达、~3H-TdR掺入法测定SMC DNA合成含量、免疫组织化
学染色法计算PDGF β-阳性指数、PCNA阳性指数。观察球囊损伤、低
频高强度超声对平滑肌细胞增殖效应的影响。结果发现，超声消融组、正
常对照组与试验对照组VSMC的C-sis表达、PDGF-βmRNA含量、PCNA
染色及~3H-TdR掺透量均无显著增加；而球囊损伤的兔VSMC各时相点均
有C-sis表达，其高峰期出现在球囊损伤1周，表达量增高了6.5倍。48h
开始出现PDGF、PCNA阳性VSMC细胞，1周时相点达到峰值。72h开
始氚掺透值持续升高，至1周达高峰。
采集正常人静脉血2ml制备为全血细胞凝块20例并行重量测定。应
用40KHz，18W/cm~2脉冲式超声对全血细胞凝块消融。消融后取沉淀涂
片，显微镜下检查碎块大小，并与红细胞直径比较。结果发现，超声能量
释放15秒内血栓完全溶解，溶解速度为0二兆土0刀N七。显微镜下检查
90％的碎片直径小于红细胞直径。
应用低频高能超声通过导管技术对急性心肌梗死、陈旧性心肌梗死
及其PTCA失败的患者进行消融，观察消融前后闭塞相关血管（IRA）TIMI
血流改变并利用 SHIMADZU Dghtex a 2400计算机分析系统测量残余狭
窄程度，检测手术前后CK－MB、心电图ST段及临床症状的改变，评价
低频高能超声血管成形术治疗心肌梗死的可行性。测定消融前后静脉血中
PL＊P＊T、卜PA、PA 的含量及观察超声消融中有无冠状动脉痉挛。撕
裂等影像学改变。结果发现，10例 AMI患者中消融后 9例 IRA达到 TIMI
血流3级，开通率为90％（9／10）。10分钟后9例患者胸痛消失、ST段
下降）50％，CK－MB峰值明显前移（5石士1．二小时）。2例患者超声消融
后冠状动脉造影闭塞相关血管管腔大于非狭窄段，30分钟后造影残余狭
窄分别为 24o、180。8例 OMI患者中，7例消融后 IRA达 TIMI血流 3
级，开通率为87．5％（／8），30分钟后造影闭塞相关血管TIMI仍为3
级。术后30分钟缺血性盯段下移明显好转（上移350o）。5例常规PTCA
失败患者经超声消融，IRA均达 TIMI3级，残余狭窄为 64石土 12石4％。
低频高能超声通过导管技术对冠脉重度狭窄进行消融，比较消融前
后冠脉狭窄程度的改变，分析手术前后常规心电图ST段改变，手术前后
运动试验测定诱发心绞痛所需时间、运动诱发 ST段下降 0．lmV所需时间、
运动诱发ST段下降最大幅度的比较。结果发现，15支狭窄口75％的血管
消融后残余狭窄为 43．03 i 15．49o，较术前降低 42．030（43．03士
15．49％VS85．83土5．44％，p＜0．05），5例消融后残余狭窄＜30％ （3．33％，
5／15）。术后心电图缺血性ST段压低较术前明显好转。术后运动诱发心绞
痛所需时间及运动诱发 ST段下降 0．lmV所需时间、运动诱发 ST段下降
最大幅度与手术前比较均有显著差异（P＜0．01）。
本研究结论：1．低频高能超声作用后VSMC的增生、迁移无显著改
变。2．体外实验及临床病例研究证实低频高能超声能有效溶解新鲜及陈旧
性血栓，无血管损伤、微栓塞等严重并发症，对凝血、纤溶系统无不良影
Vll
￡
响。3．低频高能超声血管成形术治疗AMI、OMI，可使IRA早期再通，
恢复TIMI级血流，是一种新的冠脉血运重建方式。4．血管闭塞时间长，
常规PTCA失败的病例，超声血管成形术能成功再通闭塞血管，提高PTCA
的成功率。5．超声能量可以有效裂解粥样硬化斑块，但仍然存在血管残余
狭窄；与球囊扩张联合应用能够降低所需压力，改善术后再狭窄。6．低频
高能超声的血管舒张作用，提高了超声血管成形术的可操作性及安全性。
An experimental and clinical study on angioplasty with lowfrequency and high-energy ultrasounds
Ultrasonic angioplasty, as a new approach for reconstruction of blood supply, has attracted attention from researchers at home and abroad in recent years. For this technique, such effects as mechanical vibration and cavitation etc. exerted by low frequency and high-energy ultrasounds (LFHEU) are employed to restore potency of blood vessels by splitting atherosclerotic plaques and dissolving thrombi. Meanwhile, the technique does not damage normal vascular structure. This study was designed to investigate angioplasty with LFHEU. The purposes and brief procedures are as follows: 1) After vascular smooth muscle cells (VSMC) in an animal model were treated with LFHEU, expression of C-sis and platelet-derived growth factor (PDGF) and proliferation state of the cells were evaluated to determine effects of LFHEU on proliferation of smooth muscle cells. 2) LFHEU was used to dissolve panhematic thrombi formed in vitro and those in patients with acute myocardial infarction or old myocardial infarction to determine its safety and efficiency in dissolving thrombi. 3) LFHEU was used to treat serious stenosis of the coronary artery to investigate its dissolving effects on atherosclerotic plaques.
In this study, rabbits were randomized into normal control group (group A), experimental control group (group B), balloon-injured group (group C) and ultrasonic dissolved group (group D). After the injury in carotid artery, the target segment of the common carotid artery with a length of 4 cm in rabbits in the latter two groups was extracted at 48, 72, 96, 120 hours and 1 and 2 weeks, respectively. The segment was divided into 4 parts with a length of approximately 1 cm in each. Expression of C-sis mRNA was determined by RT-PCR, synthesis and content of DNA in smooth muscle cells measured by 3H-TdR incorporation and positive indexes of PDGF-~ and PCNA by PDGF-~
and PCNA immunohistochemical staining to determine effects of balloon
injury and LFHEU on proliferation of smooth mu5cle cel1s. It was fOund that
there were no expression of C-sis and significant increase in the conteflt of
PDGF-0, PCNA staining and incorporation of 3H-TdR in Group A, Group B
and Group D. In Group C, typical expression of C-sis of cytokines encoding
PDGF-0 appeared and its peak was found in l week after the injury. The
expression intensity was increased for 6.5 times. PDGF-positive smooth
muscle ce1ls began to aPpear at 48 hours and the number reached its peak at 1
week after the injury. Incorporation value of tritium began to be continuously
elevated in 72 hours and reached its peak at 1 week after the injury.
Venous blood of 2 ml was collected from volunteers to prepare 20
panhematic c1ots. Then the colt was weighed. Ultrasounds of 40 KHz and l8
Wcm2 was used to dissolve the clots till its disaPpearance. After the dissolved
substance was made stationary, the supernatant was discarded and sediment
col1ected for smear examination under the microscope. Microscopic
examination revealed that the diameter of 90% of pieces produced in dissolve
was smaller than that of red blood cells and prepared panhematic clots were
completely dissolved in l5 seconds (dissolving speed = 0. 13 8 i 0.018g/s).
LFHEU was introduced via catheterization to treat patients with acute
myocardial infarction, old myocardial infarction and those with old myocardial
infarction in whom PTCA failed. Degree of residual stenosis was measured and
analyzed with SHIMADZU Digitex a 2400 computerized analyzing system and
changes in blood flow in infarction-related arteries (IRA), CK-MB after the
treatment, ST segmeni in ECG and clinical manifestations were observed to
evaluate feasibility of using angioplasty with LFHEU to treat myocardial
infarction. Safety of ultrasonic angioplasty was exp1ored by measuring contents
of PT, APTT t-PA and PAI in venous blood before and after the treatment to
determine whether there were imaging changes such as coron
引文
1．唐其东，林曙光，王若洁．C-sis反义寡核苷酸局部干预抑制主动脉损伤后内膜增生，中华心血管病杂志．2000；28(1)：69-71
2. Lindner V, Giachelli CM, Schwartz SM, et al. A subpopulation of smooth muscle cell in injured rat artery expresses platelet-derived growth factor-B chain mRNA. Circ Res. 1995; 76:951-957
3. Kosteer R, Windstetter U, Uberfuhr P, et al. Ehance migratory activity of vascular smooth muscle cells with high expression of platelet-derived growth factor A and B. Angioloty. 1995; 46:173-183
4. Shi ZR, Itzkowitz SH, Kim YS. A comparsion of three immunoperoxidas techniquse for antigen detection in colorectal carcinoma tissues. J Histochem Cytochem. 1988.36:317-322
5. Bauters C, Isner JM. The bioloty of restenosis. Progress Cardiovasc Dis. 1997; 40:107-116
6．魏英杰，丁金凤，许有无等．血管戌形术后血管平滑肌细胞增殖相关ESTs的筛选和克隆．基础医学研究．1999；7(4)：352-356
7．潘晓明．与增殖相关的再狭窄分子病理研究进展．国外医学·心血管疾病分册．2000；27(2)：67-70
8．谢子安，黄无伟．球囊扩张后再狭窄形成机制研究的最新进展．中国介入心脏病学杂志．1999；7(2)：93-95
9．唐其东，林曙光，林秋雄．C-sis反义寡脱氧核苷酸抑制兔主动脉平滑肌细胞增殖的时效关系．中国动脉硬化杂志．1998；6(3)：206-210
10. Hanke H, Strohscheider T, Oberhoff M, et al. Time course of smooth muscle cell proliferation in the intima and media of arteries following experimental angioplasty. Circ Res. 1990; 67:651-659
11．蒋利，陈万春，金立仁．细胞增生与实验性血管成形术后再狭窄关系的研究．上海医学．1998；21(3)：137-138
12. Bravo R. Macdomald-Bravo H. Existence of two population of cyclin/proliferating cell nuclear antigen during the cell cycle: association with DNA replication sites. J Cell Biol. 1987, 105:1549
13. Zeymer U, Fishbein Mc. Forrester JS, et al. Proliferating cell nuclear antigen immunohistochemistry in rat aorta after balloon denudation. Am J pathol. 1992; 141:685
14. Pichering JG, Weir L, Jekanowski J, et al. Proliferative activity in peripheral and coranary atherosclerotic plaque among patients undergoing percutaneous revasculariztion. J Clin Invest. 1993; 91: 1469
15. Stadius ML, Gown AM, Kernoff R. et al. Cell proliferation after balloon injury of iliac arteries in the cholesterol-fed New Zealand white rabbit. Atheroscler Thromb. 1994; 14:727
16．祝辉，周作民，林敏等．类固醇生成因子-1 与青春期小鼠睾丸P450scc mRNA水平的相关性研究．中国男科学杂志．1999；13(2)：69-71
17．杨银辉，付小兵，王亚平等．定量PCR技术检测增生性瘢痕组织纤维连接蛋白的基因表达．中华整形烧伤外科杂志．1998；14(6)：404-406
18. Giese NA., Marijianowski MHM., McCook O., et al. The role of alpha and beta platelet-derived growth factor receptor in vascular response to injury in nonhuman primates. Arterioscler Thromb Vasc Biol. 1999; 19:900-909
19. Takada M., Tanaka H., Yamada T., et al. Antibody to thrombin receptor inhibits neointimal smooth muscle cell accumulation without causing inhibition of platelet aggregation or altering hemostatic parameters after angioplasty in rat. Circ Res. 1998; 82(9): 980-987
20. Gordon D., Reidy MA., Benditt EP.,et al.Cell Proliferation in Human Coronary Arteries.Proc of Natl Acad Sci USA. 1990; 87:4600-4604
21. Karas SP, Gravanis MB, Santoian EC, et al. Coronary intimal proliferation after balloon injury and stenting in swine: An anmial model of restenosis. J Am Coll Cardiol. 1992, 20:476-474
22．欧阳平，刘伊丽，许顶立等．应用PTCA导管制作大鼠颈总动脉新生新生内膜增殖模型．第一军医大学学报．1999；19(4)：306-307
23．杨和平，欧各生，刘革修等．内毒素对猪主动脉内皮细胞瑞斯托霉素辅助因子(vwf)分泌和C-sis mRNA表达的影响．基因医学与临床．1994；62-63
24．黄红林，陈临溪，朱炳阳等．绞股蓝总皂对内毒素、氧自由基介导血管内此细胞表达C-sis基因和调节平滑肌细胞增殖的影响．中国药理学通报．1999；15(4)：325-328
25. Beatt KJ, Serruys PW, Hugenhotts PG. Restenosis after coronary angioplasty: new standards for clinical studies. J Am Coll Cardiol. 1990; 15:491-498
26．陈纪言，李光，周颖玲等．低能量红激光局部照射预防血管成形术后再狭窄的实验研究．中华心血管病杂志．1999；27(3)：224-227
27. De Meyer GRY,Bult H,Ustunes L,et al.Vasoconstrictor responses after neointima fomation.Br J Pharmacol,1994,112:471.
28. Wilensky RL, March KL, Gradus-Pizlo I. et al. Vascular injury,repair, and restenosis after percutaneous transluminal angioplasty in the atherosclerotic.Circulation. 1995; 92:2995-3005
29. Amal JF,Yamin J,Dockery S,et al. Regulation of nitricoxide synthase Mrna,protein and activity during cell growing. Cell Physiol, 1994,36:c1381.
30. Shi Y,Pieniek M,Fard A,et al. Adventitial remodeling after coronary arterial injury. Circulation, 1996,93:340-348.
31. Rosenshein U, Rozenszajn LA, Bernheim, et al. Safety of coronary ultrasound angioplasty: Effectes of sonication on intact canine coronary artieres. Cathet Cardiovasc Diagn, 1995,35:64-71.
2. Lindner V, Giachelli CM, Schwartz SM, et al. A subpopulation of smooth muscle cell in injured rat artery expresses platelet-derived growth factor-B chain mRNA. Circ Res. 1995; 76:951-957
3. Kosteer R, Windstetter U, Uberfuhr P, et al. Ehance migratory activity of vascular smooth muscle cells with high expression of platelet-derived growth factor A and B. Angioloty. 1995; 46:173-183
4. Shi ZR, Itzkowitz SH, Kim YS. A comparsion of three immunoperoxidas techniquse for antigen detection in colorectal carcinoma tissues. J Histochem Cytochem. 1988.36:317-322
5. Bauters C, Isner JM. The bioloty of restenosis. Progress Cardiovasc Dis. 1997; 40:107-116
6．魏英杰，丁金凤，许有无等．血管戌形术后血管平滑肌细胞增殖相关ESTs的筛选和克隆．基础医学研究．1999；7(4)：352-356
7．潘晓明．与增殖相关的再狭窄分子病理研究进展．国外医学·心血管疾病分册．2000；27(2)：67-70
8．谢子安，黄无伟．球囊扩张后再狭窄形成机制研究的最新进展．中国介入心脏病学杂志．1999；7(2)：93-95
9．唐其东，林曙光，林秋雄．C-sis反义寡脱氧核苷酸抑制兔主动脉平滑肌细胞增殖的时效关系．中国动脉硬化杂志．1998；6(3)：206-210
10. Hanke H, Strohscheider T, Oberhoff M, et al. Time course of smooth muscle cell proliferation in the intima and media of arteries following experimental angioplasty. Circ Res. 1990; 67:651-659
11．蒋利，陈万春，金立仁．细胞增生与实验性血管成形术后再狭窄关系的研究．上海医学．1998；21(3)：137-138
12. Bravo R. Macdomald-Bravo H. Existence of two population of cyclin/proliferating cell nuclear antigen during the cell cycle: association with DNA replication sites. J Cell Biol. 1987, 105:1549
13. Zeymer U, Fishbein Mc. Forrester JS, et al. Proliferating cell nuclear antigen immunohistochemistry in rat aorta after balloon denudation. Am J pathol. 1992; 141:685
14. Pichering JG, Weir L, Jekanowski J, et al. Proliferative activity in peripheral and coranary atherosclerotic plaque among patients undergoing percutaneous revasculariztion. J Clin Invest. 1993; 91: 1469
15. Stadius ML, Gown AM, Kernoff R. et al. Cell proliferation after balloon injury of iliac arteries in the cholesterol-fed New Zealand white rabbit. Atheroscler Thromb. 1994; 14:727
16．祝辉，周作民，林敏等．类固醇生成因子-1 与青春期小鼠睾丸P450scc mRNA水平的相关性研究．中国男科学杂志．1999；13(2)：69-71
17．杨银辉，付小兵，王亚平等．定量PCR技术检测增生性瘢痕组织纤维连接蛋白的基因表达．中华整形烧伤外科杂志．1998；14(6)：404-406
18. Giese NA., Marijianowski MHM., McCook O., et al. The role of alpha and beta platelet-derived growth factor receptor in vascular response to injury in nonhuman primates. Arterioscler Thromb Vasc Biol. 1999; 19:900-909
19. Takada M., Tanaka H., Yamada T., et al. Antibody to thrombin receptor inhibits neointimal smooth muscle cell accumulation without causing inhibition of platelet aggregation or altering hemostatic parameters after angioplasty in rat. Circ Res. 1998; 82(9): 980-987
20. Gordon D., Reidy MA., Benditt EP.,et al.Cell Proliferation in Human Coronary Arteries.Proc of Natl Acad Sci USA. 1990; 87:4600-4604
21. Karas SP, Gravanis MB, Santoian EC, et al. Coronary intimal proliferation after balloon injury and stenting in swine: An anmial model of restenosis. J Am Coll Cardiol. 1992, 20:476-474
22．欧阳平，刘伊丽，许顶立等．应用PTCA导管制作大鼠颈总动脉新生新生内膜增殖模型．第一军医大学学报．1999；19(4)：306-307
23．杨和平，欧各生，刘革修等．内毒素对猪主动脉内皮细胞瑞斯托霉素辅助因子(vwf)分泌和C-sis mRNA表达的影响．基因医学与临床．1994；62-63
24．黄红林，陈临溪，朱炳阳等．绞股蓝总皂对内毒素、氧自由基介导血管内此细胞表达C-sis基因和调节平滑肌细胞增殖的影响．中国药理学通报．1999；15(4)：325-328
25. Beatt KJ, Serruys PW, Hugenhotts PG. Restenosis after coronary angioplasty: new standards for clinical studies. J Am Coll Cardiol. 1990; 15:491-498
26．陈纪言，李光，周颖玲等．低能量红激光局部照射预防血管成形术后再狭窄的实验研究．中华心血管病杂志．1999；27(3)：224-227
27. De Meyer GRY,Bult H,Ustunes L,et al.Vasoconstrictor responses after neointima fomation.Br J Pharmacol,1994,112:471.
28. Wilensky RL, March KL, Gradus-Pizlo I. et al. Vascular injury,repair, and restenosis after percutaneous transluminal angioplasty in the atherosclerotic.Circulation. 1995; 92:2995-3005
29. Amal JF,Yamin J,Dockery S,et al. Regulation of nitricoxide synthase Mrna,protein and activity during cell growing. Cell Physiol, 1994,36:c1381.
30. Shi Y,Pieniek M,Fard A,et al. Adventitial remodeling after coronary arterial injury. Circulation, 1996,93:340-348.
31. Rosenshein U, Rozenszajn LA, Bernheim, et al. Safety of coronary ultrasound angioplasty: Effectes of sonication on intact canine coronary artieres. Cathet Cardiovasc Diagn, 1995,35:64-71.