全反式维甲酸对球囊剥脱大鼠胸主动脉内皮后内膜增生及平滑肌细胞Cyclins、C-myc蛋白表达的影响
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摘要
目的 观察球囊剥脱动脉内皮后血管内膜增生过程，血管平滑肌细胞Vascular smooth muscle cell,VSMC)增殖细胞核抗原(proliferating cell nuclearantigen,PCNA)，细胞周期蛋白CyclinD_1、CyclinE，原癌基因C-myc蛋白表达的变化及全反式维甲酸(all-trans Retinoic Acid,ATRA)对它们的影响。探讨ATRA对VSMC增生的作用及其可能的机制，为防治动脉粥样硬化、经皮冠状动脉腔内成形术、支架植入术后再狭窄提供依据。
方法 制作球囊剥脱大鼠胸主动脉内皮模型，并随机分为假手术组(n=6)，对照组(n=24)，和ATRA治疗组(n=24)。ATRA治疗组动物自术前4天起每日给予ATRA(30mg·kg~(-1)·d~(-1))灌胃，对照组和假手术组动物每日给予同等体积芝麻油(0.5ml)灌胃至处死，分别在术后2，7，14和28d分批处死动物取主动脉，常规病理切片、HE染色，采用计算机图象处理系统，测定并比较各组管腔及新生内膜面积，计算内膜／中膜面积比，采用免疫组化染色法及计算机图像分析法分析VSMC中PCNA和CyclinD_1、CyclinE、C-myc蛋白的表达水平及ATRA灌胃对它们的影响。
结果 ①对照组血管内皮损伤后2d已有中膜VSMC的增殖移行，7d血管内膜开始增生，VSMC增殖最活跃，14d内膜明显增厚，细胞数目增多，但VSMC的增殖减弱，28d管壁中细胞外基质增加，内膜继续增厚。②与假手术组相比对照组管壁细胞中PCNA和CyclinD_1、CyclinE、C-myc蛋白的表达水平在术后2d已明显增高，并持续至术后14d。③ATRA治疗组与对照组相比，14d时，新生内膜横截面积明显减少(0.057±0.017 vs 0.150±0.030，P＜0.01)，内膜／中膜横截面积比显著下降(0.107±0.035 vs 0.274±0.050，P＜0.01)；28d时新生内膜横截面积明显减少(0.075±0.017 vs 0.173±0.030，P＜0.01)，内膜／中膜横截面积比显著下降(0.140±0.036 vs 0.284±0.050，P＜0.01)，管腔面积明显扩大(1.901±0.085 vs 1.640±0.088，P＜0.01)；④ATRA治疗组较对照组
中文摘要
PeNA和eyelinol、eyclinE、C一mye蛋白的阳性指数显著下降。
结论①球囊损伤主动脉内皮后，血管内膜明显增生，管腔狭窄。②球
囊剥脱动脉血管内皮后内膜增生过程中，管壁平滑肌细胞中PCNA和
CyelinD!、CyclinE、C一mye蛋白的表达水平增加。③ATRA能抑制VSMC的增
殖，内膜增生及管腔狭窄。④盯RA能抑制pCNA、CyelinDI、CyelinE、C一myc
蛋白的表达。⑤推测全反式维甲酸可能是通过对细胞周期的调节，抑制或阻断
血管平滑细胞的增生，起到预防冠动脉粥样硬化、经皮冠状动脉腔内成形术、
支架植入术后再狭窄的作用。
Objective To investigate the process of neointimal formation and expression of proliferating cell nuclear antigen (PCNA), CyclinD|> CyclinE s C-myc protein in the rat thoracic aorta and the effects of all-trans Retinoic Acid(ATRA) on them after balloon withdrawal injury. To determine whether ATRA can prevent restenosis after percutaneous transluminal coronary angioplasty(PTCA) and the mechanisms.
Methods Make the endothelial denuded rat thoracic aorta model by balloon withdrawal injury (BWI). The rats were randomly allocated into three groups .Group1 (n=6): non-injuried group; Group2(n=24) were dosed orally with ATRA(30mg kg-1 d-1) 4 days before BWI and up to 28 days after injury. Group 3 (n=24) were given BWI and dosed orally with an equivalent volume (0.5ml) sesame oil 4 days before BWI and continued for additional 28 days. Observe the expression of the PCNA and the CyclinD1 CyclinE C-myc protein in the injured vascular wall by immunohistochemistry at day 2,7,14,28 after injury. Analysize the change of morphology by the computer-based image analysis system at different time points.
Results (1) In control group : the migration and proliferation of VSMC had existed at day 2 after BWI. The thickening of intima had begun at day 7 after injury, and they were more significant at day 14. The proliferation of VSMC decreased at day 28,but extracellular matrix increased and the intimal thickning continued. (2)The express of PCNA and CyclinD1, CyclinE C-myc protein increased significantly at day 2 after injury and began to decrease at day 14. (3) The neointima area and the ratio of neointima to media area were significantly less in ATRA group than in control group. ATRA-mediated reductions in neointima area (0.057 + 0.017 vs 0.150 + 0.030, P<0.01) , intimal/medial area ratio (0.107 + 0.035 vs 0.274 + 0.050, P<0.01) by 14 days. ATRA-mediated reductions in neointima area (0.075 + 0.017 vs 0.173 + 0.030, P<0.01) , intimal/medial area ratio (0.140+0.036 vs 0.284+0.050, P<0.01) as well as significant increases in luminal area (1.901 +0.085 vs 1.640+0.088, P<0.01) by 28 days.(4)ATRA also
can reduce the positive index of PCNA and CyclinD1 CyclinE . C-myc protein.
Conclusion (1)Neointima proliferation and luminal area decreases occurred in balloon-injured aorta.(2)The expression of PCNA and CyclinD1, CyclinE , C-myc protein increased in the process of intimal thickening after BWI. (3) ATRA could inhibit the proliferation of the VSMC and attenuated neointima formation and luminal stenosis in the artery after balloon injury.(4)ATRA could inhibit the expression of PCNA, CyclinD1, CyclinE, C-myc protein in the artery after BWI. (5)To interfere the progress of cell cycle may be one of the mechanisms that ATRA can inhibit the restenosis after the operation of PCI.
方法 制作球囊剥脱大鼠胸主动脉内皮模型，并随机分为假手术组(n=6)，对照组(n=24)，和ATRA治疗组(n=24)。ATRA治疗组动物自术前4天起每日给予ATRA(30mg·kg~(-1)·d~(-1))灌胃，对照组和假手术组动物每日给予同等体积芝麻油(0.5ml)灌胃至处死，分别在术后2，7，14和28d分批处死动物取主动脉，常规病理切片、HE染色，采用计算机图象处理系统，测定并比较各组管腔及新生内膜面积，计算内膜／中膜面积比，采用免疫组化染色法及计算机图像分析法分析VSMC中PCNA和CyclinD_1、CyclinE、C-myc蛋白的表达水平及ATRA灌胃对它们的影响。
结果 ①对照组血管内皮损伤后2d已有中膜VSMC的增殖移行，7d血管内膜开始增生，VSMC增殖最活跃，14d内膜明显增厚，细胞数目增多，但VSMC的增殖减弱，28d管壁中细胞外基质增加，内膜继续增厚。②与假手术组相比对照组管壁细胞中PCNA和CyclinD_1、CyclinE、C-myc蛋白的表达水平在术后2d已明显增高，并持续至术后14d。③ATRA治疗组与对照组相比，14d时，新生内膜横截面积明显减少(0.057±0.017 vs 0.150±0.030，P＜0.01)，内膜／中膜横截面积比显著下降(0.107±0.035 vs 0.274±0.050，P＜0.01)；28d时新生内膜横截面积明显减少(0.075±0.017 vs 0.173±0.030，P＜0.01)，内膜／中膜横截面积比显著下降(0.140±0.036 vs 0.284±0.050，P＜0.01)，管腔面积明显扩大(1.901±0.085 vs 1.640±0.088，P＜0.01)；④ATRA治疗组较对照组
中文摘要
PeNA和eyelinol、eyclinE、C一mye蛋白的阳性指数显著下降。
结论①球囊损伤主动脉内皮后，血管内膜明显增生，管腔狭窄。②球
囊剥脱动脉血管内皮后内膜增生过程中，管壁平滑肌细胞中PCNA和
CyelinD!、CyclinE、C一mye蛋白的表达水平增加。③ATRA能抑制VSMC的增
殖，内膜增生及管腔狭窄。④盯RA能抑制pCNA、CyelinDI、CyelinE、C一myc
蛋白的表达。⑤推测全反式维甲酸可能是通过对细胞周期的调节，抑制或阻断
血管平滑细胞的增生，起到预防冠动脉粥样硬化、经皮冠状动脉腔内成形术、
支架植入术后再狭窄的作用。
Objective To investigate the process of neointimal formation and expression of proliferating cell nuclear antigen (PCNA), CyclinD|> CyclinE s C-myc protein in the rat thoracic aorta and the effects of all-trans Retinoic Acid(ATRA) on them after balloon withdrawal injury. To determine whether ATRA can prevent restenosis after percutaneous transluminal coronary angioplasty(PTCA) and the mechanisms.
Methods Make the endothelial denuded rat thoracic aorta model by balloon withdrawal injury (BWI). The rats were randomly allocated into three groups .Group1 (n=6): non-injuried group; Group2(n=24) were dosed orally with ATRA(30mg kg-1 d-1) 4 days before BWI and up to 28 days after injury. Group 3 (n=24) were given BWI and dosed orally with an equivalent volume (0.5ml) sesame oil 4 days before BWI and continued for additional 28 days. Observe the expression of the PCNA and the CyclinD1 CyclinE C-myc protein in the injured vascular wall by immunohistochemistry at day 2,7,14,28 after injury. Analysize the change of morphology by the computer-based image analysis system at different time points.
Results (1) In control group : the migration and proliferation of VSMC had existed at day 2 after BWI. The thickening of intima had begun at day 7 after injury, and they were more significant at day 14. The proliferation of VSMC decreased at day 28,but extracellular matrix increased and the intimal thickning continued. (2)The express of PCNA and CyclinD1, CyclinE C-myc protein increased significantly at day 2 after injury and began to decrease at day 14. (3) The neointima area and the ratio of neointima to media area were significantly less in ATRA group than in control group. ATRA-mediated reductions in neointima area (0.057 + 0.017 vs 0.150 + 0.030, P<0.01) , intimal/medial area ratio (0.107 + 0.035 vs 0.274 + 0.050, P<0.01) by 14 days. ATRA-mediated reductions in neointima area (0.075 + 0.017 vs 0.173 + 0.030, P<0.01) , intimal/medial area ratio (0.140+0.036 vs 0.284+0.050, P<0.01) as well as significant increases in luminal area (1.901 +0.085 vs 1.640+0.088, P<0.01) by 28 days.(4)ATRA also
can reduce the positive index of PCNA and CyclinD1 CyclinE . C-myc protein.
Conclusion (1)Neointima proliferation and luminal area decreases occurred in balloon-injured aorta.(2)The expression of PCNA and CyclinD1, CyclinE , C-myc protein increased in the process of intimal thickening after BWI. (3) ATRA could inhibit the proliferation of the VSMC and attenuated neointima formation and luminal stenosis in the artery after balloon injury.(4)ATRA could inhibit the expression of PCNA, CyclinD1, CyclinE, C-myc protein in the artery after BWI. (5)To interfere the progress of cell cycle may be one of the mechanisms that ATRA can inhibit the restenosis after the operation of PCI.
引文
1．彭章平，白菁．冠状动脉成形术后再狭窄防治研究的现状[J]．心血管病学进展，1997；18(3)：136-40．
2．高润霖，吴锡桂，陈纪林等．我国冠心病研究主要成就[J]．中华心血管病杂志，1999；27(5)：325-32。
3．高润霖．冠心病重建治疗的回顾和展望[J]．中华心血管病杂志，2000；28(1)：5-6．
4. Edelman ER, Roger C. pathobiologic response to stenting[J]. Am J Cardio 1998, 81 (7A): 4E-6E.
5. Rudiger C, Dullaeus B, Nichael J, et al. Cell cycle progression: New therapeutic target for vascular proliferative disease [J] Circulation, 1998, 98: 82-9
6．隗月，林晨，昊日，与细胞周期G1——S调控点相关的几个重要元件及其与肿瘤的关系[J]．国外医学分子生物学分册．1998．20(1)．10-13．
7. Sgambato A, Han Ek, Zhou F, et al. Overexpression of cyclin E in the HCII mouse mammary epithelial cell line is associated with growth inhibition and increased expression of P27 kipl[J]. Cancer Res, 1996, 56: 1389-90
8. Gadeau AP. Campna M, Desgranges C. Induction of cell cycle-dependent genes during cell cycle progression of arterial smooth muscle cells in culture [J]. J Cell Physiol, 1991, 146(3): 356-61.
9. Bauters C, de Groote P. Adamatidis M et al. Proto-oncogene expression in rabbit aorta after wall injury: first marker of the cellar progree leading to restenosis after angioplasty? [J]. Eur Heart J. 1992, 13(3): 556-9.
10. Spanjaard RA, Lee PJ, Sarlar S, et al. Clone 10d/BM 28(CDCL), an early S-Phage protein, is an important growth regulator of metanoma [J] Cancer Res, 1997, 57 (22); 5 122-8
11．韩锐，编．肿瘤的化学预防与治疗，北京：北京医科大学．中国协和医科大学联合出版社出版．1992；258-64．
12. Miano JM, Kelly LA, Artaeho CA, et al. All-trans retinoic acid reduces neointimal formation and promotes favorable geometric remodeling of the rat carotid artery after balloon withdrawal injury[J]. Circulation, 1998; (12): 1219-27.
13．张卫国，董果雄，候磊等．全反式维甲酸对培养大鼠主动脉血管平滑肌细胞增生及p21表达的影响[J]．新乡医学院学报，2003；20(3)：163-5．
14. Schwartz RS. Pathophysiology of restenosis: interaction of thrombosis,
15. hyperplasia, and/of remodeling [J]. Am Cardiol, 1998. 81(74) 14E-17E.
16. Anderson HR, Maeng M, Thorwest m, et al Remodeling rather than reointimal formation explains luminal narrowing after deep vessel wall injury [J]. Circulation, 1996; 93: 1716-24
17. Kimura T, Kaburagi S, Yokoi H, et al. Time course of vessel response after coronary angioplasty final results of serial ultrasound restenosis stuty[J]. Circulation, 1996; 94: Ⅰ-135.
18. Stephen GE, Mark BE, Herman KG, et al. Acute platelet inhibition with Abciximab does not reduce in-stent restenosis[J]. Circulation, 1999; 100(8): 799-806.
19. Leid M, Kastner P, Chambon EMultiplicity generates diversity in the retinoic acid signaling pathways[J]. Trends Biochem Sci, 1992; 17: 427-33.
20．杨志祥，糜漫天，张乾勇等．CyclinD1在视黄醇类化合物诱导骨髓细胞分化中的作用研究[J]．白血病2000．4；9(2)：79-81
21. Mehta K, Mcqueen T, Tucker S, et al. Inhibition by all-trans-retinotic acid of tumor necrosis factor and nitric oxid production by peritoneal macrophages[J]. J Leukoc Biol, 1994; 55: 336-42.
22. Yasui H, Nakazawa M, Morishma M, et al. Morphlogic observations on the pathogenetie process of transposition of the great arteries induced by retinoic acid in mice[J]. Circulation, 1995; 91: 2478-86.
23. Takayama K, Toshi J, Uchida M, et al. Retinoic acid differentially up-regulates the gene expression of retinoic acid receptor and isoforms in embryo and adult rats[J]. Biochem Biophys Res commun, 1996, 222(2): 395-400
24. Miano JM, Topouzis S, Majesky MW, et al. Retinoid receptor expression and cell-trans retinoic acid-mediated growth ihibition in vascular smooth muscle cells [J]. Circulation, 1996; 93: 1886-95.
25．李大主．曹林生．冯义相等．动脉内皮损伤后平滑肌细胞维甲酸受体表达及维甲酸的作用[J]．中国病理生理杂志．1999，15(6)515-516．
26. Pakala R, Benedict CR. RAR gamma agonists inhibit proliferation of vascular smooth muscle cells[J]. Cadiovasc. Pharmacol 2000 Feb; 35(2)302-8.
27. Axel DI, Frigge A, Dittmam J, et al. All-trans retinotic acid regulates proliferation, migration, differentation, and extracellular matrix turnover of human arterial smooth muscle cells[J]. Cardiovas Res. 2001 Mar 49(4) 851-62.
28. Guo W, Baluda MA, Park NH, et al. Ethand upregulates the express ion of P21 WAF 1/CIPI and prolongs G1 transtion via a p53-indepent pathway in human epithelial cells[J]. Oncogene, 1997, 15(10) 1143-9.
29. Hengstschlager M, Braun K, Soucck T, et al. Cyclin-dependent kinases at the G1→S transtion of the mammalin cell cycle[J]. Murat Res 1999, 436(1): 1-9.
30. Inaba T, Matsushime H, Valentine M, et al. Genomic organization, Chromosomal localization, and, independent expression of human cyclinD genes[J]. Genomics, 1992, 13(3): 565-74.
31. Muller H, Moromi MC,VigoE, et al. Induction of s-phase entry by E2F transcription factors regulation of cell proliferation by the E2F transcription factors[J]. Curr Opin Genet Dev, 1998, 8(1) 28-35.
32. Nevins JR, Leone G, DeGregori J, et al. Role of the Rb/E2F pathway in cell growth control[J]. J cell Physol, 1997, 173 (2): 233-36.
33. Wei GL, Krasinski K, Keamey M, et al. Temporlly and spatially coordinated expression of cell cycle regulatory factors after angioplasty[J] Circ Res. 1997, 80: 418-26
34. Zhu NL, We LT, Liu PX, et al. Downregulation of cyclinG1 expression by retrovirus-mediated antisense gene transfer inhibits vascular smooth muscle cell proliferation and neointima formation[J]Circulation. 1997, 96: 628-35
35. Wakino S Kintscher U, Kim S, et al Retinoids inhibit proliferation of human coronary smooth muscle cells by modulating cell cycle regulatiors[J]. Arterioscler Thromb Vasc Boil, 2000, 21: 746-51
36. Campan M, Desgranges C, Gadeall AP, et al. Cell cycle dependent gene expression in quiescent stimulated and asynchronously cycling arterial smooth muscle cells in culture [J]. J Cell Physiol. 1992, 150(3): 493-500.
37. Miano J, Vlasic N, Robert R, et al. Smooth muscle cell immediate-early gene and growth factor activation follows vascular injury[J]. Arterioscler Thromb, 1993, 13(2): 211-9.
38. Shichiri M, Hanson KD, Sedivy JN, et al. Effect of c-myc expression on proliferation, quiescence and the G_0 to G_1 transition in nontransformed cells[J]. Cell Growth Differ. 1993; 4, 93-104
39. Daksis JI, Lu RY, Facchini LM, et al. Myc induces cyclin D_1 expression in the absence of de novo protein synthesis and links mitogen-stimulated signal transduction to the cell cycle[J]. Oncogene. 1994; 9: 3635-45
40. Bennett MR, Littlewood TD, Hancock DC, et al. Down-regulation of the c-myc proto-oncogene in inhibition of vascular smooth-muscle cell proliferation: a signal for growth arrest? [J] Bio Chem J 1994 Sep 15; 302 (Pt 3): 701-8
41. Bennet MR, Anglin S, McEwan JR. Inhibition of vascular smooth muscle cell proliferation in vitro and in vivo by c-myc antisense digodeoxynucleotides [J]. J.Clin.Invest 1994. 93: 820-8.
42. Kipshidze N, Keane E, Stein D, et al. Local delivery of c-myc ceutrally charged antisense oligonucleotides with transport catheter inhibits myointimal hyperplasia and positively affedts vascular remodeling in the rabbit balloon injury model[J]. Catheter Cardiovasc Interv. 2001, 54(2): 247-256
43．张新霞，崔长琮，崔翰斌等．涂层支架局部导入c-myc基因反义寡核苷酸防治再狭窄的实验研究[J]．中国循环杂志2001．09．24；16：40-41．
2．高润霖，吴锡桂，陈纪林等．我国冠心病研究主要成就[J]．中华心血管病杂志，1999；27(5)：325-32。
3．高润霖．冠心病重建治疗的回顾和展望[J]．中华心血管病杂志，2000；28(1)：5-6．
4. Edelman ER, Roger C. pathobiologic response to stenting[J]. Am J Cardio 1998, 81 (7A): 4E-6E.
5. Rudiger C, Dullaeus B, Nichael J, et al. Cell cycle progression: New therapeutic target for vascular proliferative disease [J] Circulation, 1998, 98: 82-9
6．隗月，林晨，昊日，与细胞周期G1——S调控点相关的几个重要元件及其与肿瘤的关系[J]．国外医学分子生物学分册．1998．20(1)．10-13．
7. Sgambato A, Han Ek, Zhou F, et al. Overexpression of cyclin E in the HCII mouse mammary epithelial cell line is associated with growth inhibition and increased expression of P27 kipl[J]. Cancer Res, 1996, 56: 1389-90
8. Gadeau AP. Campna M, Desgranges C. Induction of cell cycle-dependent genes during cell cycle progression of arterial smooth muscle cells in culture [J]. J Cell Physiol, 1991, 146(3): 356-61.
9. Bauters C, de Groote P. Adamatidis M et al. Proto-oncogene expression in rabbit aorta after wall injury: first marker of the cellar progree leading to restenosis after angioplasty? [J]. Eur Heart J. 1992, 13(3): 556-9.
10. Spanjaard RA, Lee PJ, Sarlar S, et al. Clone 10d/BM 28(CDCL), an early S-Phage protein, is an important growth regulator of metanoma [J] Cancer Res, 1997, 57 (22); 5 122-8
11．韩锐，编．肿瘤的化学预防与治疗，北京：北京医科大学．中国协和医科大学联合出版社出版．1992；258-64．
12. Miano JM, Kelly LA, Artaeho CA, et al. All-trans retinoic acid reduces neointimal formation and promotes favorable geometric remodeling of the rat carotid artery after balloon withdrawal injury[J]. Circulation, 1998; (12): 1219-27.
13．张卫国，董果雄，候磊等．全反式维甲酸对培养大鼠主动脉血管平滑肌细胞增生及p21表达的影响[J]．新乡医学院学报，2003；20(3)：163-5．
14. Schwartz RS. Pathophysiology of restenosis: interaction of thrombosis,
15. hyperplasia, and/of remodeling [J]. Am Cardiol, 1998. 81(74) 14E-17E.
16. Anderson HR, Maeng M, Thorwest m, et al Remodeling rather than reointimal formation explains luminal narrowing after deep vessel wall injury [J]. Circulation, 1996; 93: 1716-24
17. Kimura T, Kaburagi S, Yokoi H, et al. Time course of vessel response after coronary angioplasty final results of serial ultrasound restenosis stuty[J]. Circulation, 1996; 94: Ⅰ-135.
18. Stephen GE, Mark BE, Herman KG, et al. Acute platelet inhibition with Abciximab does not reduce in-stent restenosis[J]. Circulation, 1999; 100(8): 799-806.
19. Leid M, Kastner P, Chambon EMultiplicity generates diversity in the retinoic acid signaling pathways[J]. Trends Biochem Sci, 1992; 17: 427-33.
20．杨志祥，糜漫天，张乾勇等．CyclinD1在视黄醇类化合物诱导骨髓细胞分化中的作用研究[J]．白血病2000．4；9(2)：79-81
21. Mehta K, Mcqueen T, Tucker S, et al. Inhibition by all-trans-retinotic acid of tumor necrosis factor and nitric oxid production by peritoneal macrophages[J]. J Leukoc Biol, 1994; 55: 336-42.
22. Yasui H, Nakazawa M, Morishma M, et al. Morphlogic observations on the pathogenetie process of transposition of the great arteries induced by retinoic acid in mice[J]. Circulation, 1995; 91: 2478-86.
23. Takayama K, Toshi J, Uchida M, et al. Retinoic acid differentially up-regulates the gene expression of retinoic acid receptor and isoforms in embryo and adult rats[J]. Biochem Biophys Res commun, 1996, 222(2): 395-400
24. Miano JM, Topouzis S, Majesky MW, et al. Retinoid receptor expression and cell-trans retinoic acid-mediated growth ihibition in vascular smooth muscle cells [J]. Circulation, 1996; 93: 1886-95.
25．李大主．曹林生．冯义相等．动脉内皮损伤后平滑肌细胞维甲酸受体表达及维甲酸的作用[J]．中国病理生理杂志．1999，15(6)515-516．
26. Pakala R, Benedict CR. RAR gamma agonists inhibit proliferation of vascular smooth muscle cells[J]. Cadiovasc. Pharmacol 2000 Feb; 35(2)302-8.
27. Axel DI, Frigge A, Dittmam J, et al. All-trans retinotic acid regulates proliferation, migration, differentation, and extracellular matrix turnover of human arterial smooth muscle cells[J]. Cardiovas Res. 2001 Mar 49(4) 851-62.
28. Guo W, Baluda MA, Park NH, et al. Ethand upregulates the express ion of P21 WAF 1/CIPI and prolongs G1 transtion via a p53-indepent pathway in human epithelial cells[J]. Oncogene, 1997, 15(10) 1143-9.
29. Hengstschlager M, Braun K, Soucck T, et al. Cyclin-dependent kinases at the G1→S transtion of the mammalin cell cycle[J]. Murat Res 1999, 436(1): 1-9.
30. Inaba T, Matsushime H, Valentine M, et al. Genomic organization, Chromosomal localization, and, independent expression of human cyclinD genes[J]. Genomics, 1992, 13(3): 565-74.
31. Muller H, Moromi MC,VigoE, et al. Induction of s-phase entry by E2F transcription factors regulation of cell proliferation by the E2F transcription factors[J]. Curr Opin Genet Dev, 1998, 8(1) 28-35.
32. Nevins JR, Leone G, DeGregori J, et al. Role of the Rb/E2F pathway in cell growth control[J]. J cell Physol, 1997, 173 (2): 233-36.
33. Wei GL, Krasinski K, Keamey M, et al. Temporlly and spatially coordinated expression of cell cycle regulatory factors after angioplasty[J] Circ Res. 1997, 80: 418-26
34. Zhu NL, We LT, Liu PX, et al. Downregulation of cyclinG1 expression by retrovirus-mediated antisense gene transfer inhibits vascular smooth muscle cell proliferation and neointima formation[J]Circulation. 1997, 96: 628-35
35. Wakino S Kintscher U, Kim S, et al Retinoids inhibit proliferation of human coronary smooth muscle cells by modulating cell cycle regulatiors[J]. Arterioscler Thromb Vasc Boil, 2000, 21: 746-51
36. Campan M, Desgranges C, Gadeall AP, et al. Cell cycle dependent gene expression in quiescent stimulated and asynchronously cycling arterial smooth muscle cells in culture [J]. J Cell Physiol. 1992, 150(3): 493-500.
37. Miano J, Vlasic N, Robert R, et al. Smooth muscle cell immediate-early gene and growth factor activation follows vascular injury[J]. Arterioscler Thromb, 1993, 13(2): 211-9.
38. Shichiri M, Hanson KD, Sedivy JN, et al. Effect of c-myc expression on proliferation, quiescence and the G_0 to G_1 transition in nontransformed cells[J]. Cell Growth Differ. 1993; 4, 93-104
39. Daksis JI, Lu RY, Facchini LM, et al. Myc induces cyclin D_1 expression in the absence of de novo protein synthesis and links mitogen-stimulated signal transduction to the cell cycle[J]. Oncogene. 1994; 9: 3635-45
40. Bennett MR, Littlewood TD, Hancock DC, et al. Down-regulation of the c-myc proto-oncogene in inhibition of vascular smooth-muscle cell proliferation: a signal for growth arrest? [J] Bio Chem J 1994 Sep 15; 302 (Pt 3): 701-8
41. Bennet MR, Anglin S, McEwan JR. Inhibition of vascular smooth muscle cell proliferation in vitro and in vivo by c-myc antisense digodeoxynucleotides [J]. J.Clin.Invest 1994. 93: 820-8.
42. Kipshidze N, Keane E, Stein D, et al. Local delivery of c-myc ceutrally charged antisense oligonucleotides with transport catheter inhibits myointimal hyperplasia and positively affedts vascular remodeling in the rabbit balloon injury model[J]. Catheter Cardiovasc Interv. 2001, 54(2): 247-256
43．张新霞，崔长琮，崔翰斌等．涂层支架局部导入c-myc基因反义寡核苷酸防治再狭窄的实验研究[J]．中国循环杂志2001．09．24；16：40-41．
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