氯沙坦对血管内皮损伤后血小板活化及AngⅡAT_1受体表达的影响

Effects of losartan on the platelet activation and expression of angiotensin Ⅱ AT_1 receptor mRNA after vascular balloon injury in rats

目的:研究球囊损伤血管后内膜增生的过程、血小板活化水平、血管紧张素ⅡAT1受体mR-NA的变化及氯沙坦对其的影响。方法:随机将72只雄性Wistar大鼠分为对照组、手术组和氯沙坦治疗组,每组24只。分别在术后3、7、14和28d,采用组织学检查、放射免疫法和RT-PCR技术检测内膜增生的情况、血小板表面GMP-140的数量、AT1受体mRNA的水平及氯沙坦(30 mg.kg-1.d-1)灌胃对其的影响。结果:①AT1受体mRNA于术后3 d明显增高(P<0.05),并持续至术后14 d(P<0.01);②GMP-140于术后3 d明显升高,术后7 d开始下降(P<0.01);③内皮损伤术后3 d已有增殖的血管平滑肌细胞(VSMC)移行至内膜层,7 d内膜开始增生,14 d VSMC的增殖及内膜增生更为明显,28 d VSMC的增殖明显减弱,细胞外基质增加,内膜继续增生;④应用氯沙坦后AT1受体mRNA表达增加(P<0.05,P<0.01),但血小板表面GMP-140的数量和VSMC的移行、增殖减弱,内膜增生程度减轻(P<0.05,P<0.01)。结论:血管内皮损伤后内膜增生的过程中血小板活化、AT1受体mRNA表达增加,氯沙坦能抑制血小板的活化及VSMC的移行、增殖,减轻内膜增生的程度,上调AT1受体mRNA的表达。

Objective： To investigate the process of neointimal formation, level of platelet activation, expression of angiotensin Ⅱ AT1 receptor mRNA and effects of losartan on them after vascular balloon injury in rats. Methods： Forty-eight male Wister rats were randomly given aortic balloon injury by 2F balloon catheters （ n = 24）, aortic balloon injury plus losartan （30 mg·kg^-1·d^-1 ） from 1 day before injury to 28 days after injury, and compared with the controls （ n = 24）. The process of intimal thickening, number of platelet GMP-140 and level of AT1 receptor mRNA were investigated at day 3,7,14 and 28 after injury by histological method, radioimmunological method and RT-PCR technique, respectively. Results： ① The expression of AT1 receptor mRNA increased significantly at day 3 after balloon injury and remained high at day 14 （P 〈 0.01）. ②The number of platelet GMP-140 was high at day 3 and began to decrease at day 7 after injury（ P 〈 0.01 ）. ③The migration and proliferation of vascular smooth muscle cells（VSMC） had existed at day 3 after balloon injury.The thickening of intima happened at day 7 after injury （ P 〈 0.01） and acted more significant at day 14 （ P 〈 0.01）. The proliferation of VSMC decreased at day 28, but extracellular matrix increased and intimal thickening continued （ P 〈 0.01 ）. ④In losartan treated group, the number of platelet GMP-140, proliferation of VSMC and intimal thickening reduced （P 〈 0.01）, but the level of AT1R mRNA increased （ P 〈 0.01）. Conclusion： The expression of AT1R mRNA and the number of platelet GMP-140 increase in the process of intimal thickening after balloon injury. Losartan inhibits the activation of platelet and intimal thickening, but upregulates the expression of AT1 R mRNA.