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氯沙坦对血管内皮损伤后血小板活化及AngⅡAT1受体表达的影响吴逸南

吴逸南,葛志明,李永红,李方,张成秋,张运   

  1. 山东大学齐鲁医院心内科,山东 济南250012
  • 收稿日期:2005-07-11 修回日期:1900-01-01 出版日期:2006-04-24 发布日期:2006-04-24

Effects of losartan on the platelet activation and expression of angiotensin Ⅱ AT1 receptor mRNA after vascular balloon injury in rats

WU Yi-nan, GE Zhi-ming, LI Yong-hong, LI Fang, ZHANG Cheng-qiu, ZHANG Yun   

  1. Department of Cardiology, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China
  • Received:2005-07-11 Revised:1900-01-01 Online:2006-04-24 Published:2006-04-24

摘要: 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mRNA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:① AT1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);② GMP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。

Abstract: Objective: To investigate the process of neointimal formation, level of platelet activation, expression of angiotensinⅡ 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). ② The number of platelet GMP140 was high at day 3 and began to decrease at day 7 after injury(P<0.01). ③ The 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).④ In 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 AT1R mRNA.

Key words: Balloon injury, Receptors, angiotensin, Platelet avtivation, Losartan, Rat, Wistar

中图分类号: 

  • Q786
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