L-精氨酸抑制球囊损伤后大鼠血管内膜增生的机制研究

摘要

Objective　To determine whether the anti-proliferation effect of L-arginine is due to inhibiting the expression of cyclin dependent kinase-2 (CDK2)、 CyclinE and proliferation cell nuclear antigen (PCNA) in blood vessel after balloon injury. Methods　Rats were randomized into three groups: Group S (sham operation group), Group C (balloon injury control group) and Group L (balloon injury+L-arginine group). After 14 days, blood samples were collected for biochemical studies, and the thoracic aortas were harvested for immunohistochemistry. The expression of CDK2、 CyclinE and PCNA were measured by means of computer image analayzer. Results　The levels of plasma nitric oxide (NO) in group C were significantly lower than those in group S. Compared with group C, the levels of plasma NO increased (P<0.01), the neointima area reduced by 59.1% (P<0.01) and the positive expression indexes of CDK2、 CyclinE and PCNA decreased by 36.1%, 46.3% and 76.2% respectively in group L (P all <0.01). Conclusion　Inhibitory effect of L-arginine on CDK2、 CyclinE and PCNA high expression may be one of the mechanisms of the anti-proliferation effect of L-arginine after balloon injury.%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14 d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NO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。