ADMA对自发性高血压大鼠血小板聚集的影响及氯沙坦的干预作用  

Effect of asymmetric dimethylarginine on platelet-aggregation and losartan intervention in spontaneous hypertensive rat models

作　　者：夏珂[1] 李岱[2] 赵震宇[3] 杨天崙[1] 

机构地区：[1]中南大学湘雅医院心内科,长沙410078 [2]中南大学药学院,长沙410078 [3]中南大学临床药理研究所,长沙410078

出　　处：《中南大学学报（医学版）》2006年第5期645-649,654,共6页Journal of Central South University ：Medical Science

摘　　要：目的:以自发性高血压大鼠为动物模型,氯沙坦为干预药物,探讨非对称性二甲基精氨酸(asymmetricdimethylarginine,ADMA)对血小板聚集的影响以及氯沙坦的干预作用。方法:自发性高血压大鼠(SHR)随机分为SHR组、L-精氨酸组(SHR+L-精氨酸)、氯沙坦组(SHR+氯沙坦);另设一组京都Wistar大鼠作为对照组(WKY),每组大鼠均16只。所有大鼠自由饮水、饮食,WKY组与SHR组每天10mL/(kg·d)蒸馏水灌胃1次,L-精氨酸组与氯沙坦组分别用1.0g/(kg·d)的L-精氨酸、30mg/(kg·d)的氯沙坦钾溶解于10mL蒸馏水灌胃1次,连续2周。分别检测血小板聚集率(Pt-Ag),血浆与血小板NO,NOS,血浆与血小板ADMA浓度;另取SD大鼠血小板,分别用上述4组大鼠血管内皮孵育血小板,检测Pt-Ag。结果:(1)SHR组Pt-Ag显著高于WKY组(P<0.01);L-精氨酸与氯沙坦干预后的Pt-Ag与SHR比较均显著降低(P<0.01);(2)SHR组血浆NO浓度与血小板NO含量均显著低于WKY组(P<0.05);L-精氨酸与氯沙坦干预后NO均显著升高(P<0.05);(3)SHR组血浆与血小板NOS活性显著低于WKY组(P<0.05);L-精氨酸与氯沙坦干预后均显著升高NOS活性(P<0.01);(4)SHR组血浆ADMA浓度与血小板ADMA含量显著高于WKY组(P<0.05);L-精氨酸与氯沙坦干预后均显著降低ADMA(P<0.05);(6)血管内皮体外孵育血小板后,与对照组相比,WKY内皮组Pt-Ag显著降低(P<0.05);SHR内皮组Pt-Ag显著增加(P<0.05);与SHR内皮组相比,L-精氨酸与氯沙坦内皮组Pt-Ag均显著降低(P<0.01,P<0.05)。结论:(1)高血压大鼠ADMA浓度升高导致NOS活性降低和NO合成减少,这可能是引起血小板聚集率增高的重要原因;(2)氯沙坦在降压的同时显著降低血小板聚集率,该作用可能是通过降低体内ADMA浓度、增加NOS活性和NO合成而实现的。Objective To evaluate the effect of asymmetric dimethylarginine （ADMA） and the results of losartan intervention on platelet-aggregation in spontaneous hypertensive rats. Methods Spontaneous hypertensive rats （SHR） were randomly assigned into 3 groups： SHR control group, L-arginine treatment group （L-arg） and losartan （los） treatment group, each group consisting of 16 rats. Another 16 Wistar Kyoto rats （WKY） served as normal control group. The L-arginine and losartan treatment groups received 1.0 g/kg L-arginine or 30 mg/kg losartan in 10 mL/kg distilled water daily through gastric tube for 2 weeks respectively, while the SHR and WKY groups received distilled water alone. All the rats took tap water and standard feed freely during the experimental period. Systolic blood pressure （SBP） was monitored by the tail-cuff method. At the end of the 2- week intervention, all the rats were sacrificed and the blood samples were collected from the carotid artery. The platelet-aggregation-rate, NO levels, eNOS activity, and ADMA levels both in the plasma and the platelets were measured. We got other platelet samples from the SD rats and incubated the platelets with blood vascular endothelium from the above 4 groups of experimental rats and the platelet-aggregation-rate was monitored as well. Results （ 1 ） Systolic blood pressure of the SHR was significantly higher, compared with that of the WKY （ P 〈 0.01 ） , which were significantly reduced both in the L-arginine and losartan groups （P 〈 0.01 ）. （2） Platelet-aggregation-rate of the SHR was significantly higher, compared with that of WKY （ P 〈 0.01 ） , which was significantly reduced both in the L-arginine and losartan groups （P 〈 0.01 ）. （3） NO levels both in the plasma and the platelets of the SHR were lower, compared with those of the WKY （ P 〈 0.05 ） ; and were elevated significantly both in the L-arginine and losartan groups, compared with those of the SHR （ P 〈 0.05） ; （4） Both the plasma and

关 键 词：高血压 血小板聚集率 一氧化氮 一氧化氮合酶 非对称性二甲基精氨酸 氯沙坦 血管内皮 

分 类 号：R544.1[医药卫生—心血管疾病]