L-精氨酸抑制球囊损伤后大鼠血管内膜增生的机制研究L-arginine attenuates proten expression of related cell cycle regulatory factors in rats after balloon injury
聂晓敏,刘瑞云,黄振文
摘要(Abstract):
目的 探讨L-精氨酸抗血管内膜增生的作用机制是否与影响球囊损伤后血管中细胞周期调控基因、细胞周期依赖性激酶2(CDK2)、细胞周期蛋白 E(CyclinE)和增殖细胞核抗原(PCNA)的表达有关。方法 21只大鼠随机分为S组(假手术组),C组(球囊损伤对照组)及L组(球囊损伤+L-精氨酸组)各组 n= 7。术后 14d采血测血浆一氧化氮(NO)水平,并处死大鼠取其胸主动脉,测新生内膜面积,采用免疫组化和计算机图像分析法测CDK2、CyclinE和PCNA的表达水平。结果 C组的血浆NO水平明显低于S组,与C组相比,L组的血浆N0水平增高(P<0.01),新生内膜面积减少59.1%(P<0.01),CDK2、CyclinE及PCNA的阳性表达指数分别降低36.1%,46.3%和76.2%((P均<0.01)。结论 L-精氨酸抑制球囊损伤后血管中CDK2、CyclinE及PCNA的高表达可能是其抑制血管损伤后内膜增生的分子机制之一。
关键词(KeyWords): L-精氨酸;球囊损伤;细胞周期调控
基金项目(Foundation): 河南省科技攻关项目(971200100)
作者(Author): 聂晓敏,刘瑞云,黄振文
参考文献(References):
- 1 Madellan WR, Majesky NW. Cell cycle regulators in vascular disease.Circulation, 1997,96: 1717-1719.
- 2 Vadiveloo PK, Filonzi EL, Stanton HR, et al. G_1 phase arrest ofhuman smooth muscle cells by heparin, IL-4 and cAMP is linked torepression of cyclin DI and cdk2. Atherosclerosis, 1997, 133:6l-69.
- 3 Tarry WC, Makhoul RG. L-arginine improves endothelium-dependent vasorelaxation and reduces intimal hyperplasia after balloon angioplasty.Arterioscler Thromb,1994, 14:938-943.
- 4 Braun-Dullaeus RC, Mann MJ, Dzau VJ. Cell cycle progression: newtherapeutic target for vascular proliferative disease. Circulation, 1998,98:82-89.
- 5 Wei GL, Krasiki K, Kearney M, et al. Temperally and spatiallycoordinated expression of cell cycle regulatory factors after angioplasty.Cir Res, 1997,80:418-426.
- 6 Sarkr R, Gordon D, Stanley JC, et al. Cell cycle effects of nitric oxideon vascular smooth muscle cells. Am J Physiol, 1997, 272: H18lO-H1818.
- 7 Guo K, Andres V, Walsh K. Nitric oxide-induced downregulation ofcdk2 activity and cyclinA gene transcription in vascular smooth musclecells. Circulation, 1998,97:2066-2072.
- 8 Ishida A, Sasaguri T, Kosaka C, et al. Inducion of the cyclin-dependent kinase inhibitor P21 (Sdil/Cipl/Cafl) by nitric oxide-generating vasodilator in vascular smooth muscle cells. J Biol Chem,1997, 272: l0050-10057.
- 9刘兴鹏,曹林生.一氧化氮与经皮腔内冠状动脉成形术后血管 再狭窄的预防.心血管病学进展,2000,21:105-107.