NO前体—左旋精氨酸相关肽对大鼠血小板聚集、血栓形成及血浆NO、cGMP、PGI_2的影响

Effect of nitric oxide precursor-L-arginine-related peptide on rat platelet aggregation, thrombsis and the plasma levels of nitric oxide, cyclic guanine monophosphate and prostacyclin

目的 观察左旋精氨酸相关肽 (L -ArgX)对大鼠血小板聚集、血栓形成及血浆一氧化氮 (NO)、环磷酸鸟苷 (cGMP)和前列环素 (PGI2 )的影响。方法 2 4只SD雄性大鼠随机分为 2组 ,分别灌服L -ArgX 6 1 4mg/kg·b w及对同体积空白对照液 ,每日 1次 ,共 8d。 8d后观察大鼠血小板聚集 (比浊法 )、血栓形成 (丝线法 )及血浆NO、cGMP、PGI2 浓度的变化 (分光光度法和放免法 )。结果L -ArgX可显著抑制大鼠血小板聚集率及血栓形成 ,使血浆NO、cGMP浓度升高 ,血浆PGI2 浓度有升高趋势 ,但与对照组相比无统计学差异。结论L -ArgX可抑制血小板聚集 ,其作用机制可能由一氧化氮 -环磷酸鸟苷代谢通路(NO -cGMPpathway)所介导 ,此外尚可能有其它作用机制参与。L -ArgX可视为一种NO前体 ,具有抗凝血作用。

Objective To observe L-Arginine related peptide (L-Arg X)'seffect on rat's platelet aggregation, thrombsis and the plasma level of nitric oxide(NO), cyclic GMP(cGMP) and prostacyclin(PGI 2) Methods Twenty-four Sprague Dewley rats were divided into 2 groups randomly One group was given L-Arg X (61 4 mg·kg -1 ·d -1 ) orally and the other was given placebo Blood was taken from abdominal aorta with a plastic catheter 8 days after treatment Platelet aggregation was measured by turbidimetric method Plasma level of cyclic GMP and prostacyclin was evaluated by radioimmunoassay and nitric oxide by spectrophotometric determination Common carotid artery-external jugular vein bypass was made after rats were anesthetized and weight of wet thrombus was measured with highly sensitive electrical scale Results Platelet aggregation activation decreased compared with placebo (10 75%±3 62)% vs 32 8%±6 62%, P<0 05) adenosine diphosphate(ADP)-inducedby; (11 83%±3 98% vs 34 64%±6 54%, P<0 05) arachidonic acid(AA) induced; weight of wet thrombus lessened (4 0±1 0 vs 7 0±1 7 mg, P<0 05); plasma concerntration of nitric oxide and cyclic GMP increased (22 4±6 1 vs 16 3±2 5 (mol/L, P<0 05; 10 3±2 3 vs 7 0±1 0 nm/L, P<0 05); prostacyclin saw increasing trend but showed no significance compared with placebo(4 76±1 4 vs 4 73±1 84 ng/L, P>0 05) Conclusion The L-Arg X peptide shows strong antiplatelet function compared with placebo It can reduce thrombus weight in vivo, inhibit platelet aggregation in vitro and increase plasma concerntration of nitric oxide and cyclic GMP significantly Its antihemostatic and antithrombotic function might be mediated by L-arginine-nitric oxide-cyclic GMP metablism passway Although plasma level of prostacyclin shows no significant changes, its mechanism remains unknown and needs to be further studied L-Arg X peptide might be regarded as a nitric oxide precursor Because of its beneficial cardiovascular protection with simple chemical structure and evident antithrombotic activation, its phamaceutical value to cardiovascular disease is expected to be further explored