同型半胱氨酸血症血小板及内皮细胞活性的体内研究  

Acute hyperhomocysteinaemia promotes activation of both platelets and endothelium in normal subjects

作　　者：范伯丽[1] 董会奕[1] 蒋宝琦[1] Brian Tomlinson 

机构地区：[1]北京大学深圳医院心血管内科,深圳518036 [2]香港中文大学内科及药物治疗学系

出　　处：《中华心血管病杂志》2004年第2期126-130,共5页Chinese Journal of Cardiology

摘　　要：目的　探讨轻中度同型半胱氨酸血症作为心血管疾病新的重要危险因子对血小板活性 ,内皮细胞功能及体内氧化状态的影响。方法　应用安慰剂自身对照交叉设计方法 ,蛋氨酸负荷实验诱导 15个正常个体轻中度同型半胱氨酸血症 ,检测轻中度同型半胱氨酸血症对血小板纤维蛋白原结合及血小板膜P选择素表达 ,内皮细胞依赖的血管舒张 ,内皮细胞因子及体内氧化指标硫巴比妥酸反应物和结合二烯的影响。结果　蛋氨酸负荷后 ,血浆同型半胱氨酸水平显著升高 [(6 5 6±1 83) μmol L比 (15 2 0± 3 0 1) μmol L ,P <0 0 0 1],并伴随范登伯因子 ,血浆凝血酶活化因子抑制剂 1和血浆 β 血栓球蛋白水平的显著升高 [分别为 (6 8± 33) %比 (86± 13) % ,P <0 0 5 ,(35± 11)ng ml比(6 9± 38)ng ml,P <0 0 5 ,(78± 5 0 )U ml比 (12 5± 5 0 )U ml,P =0 0 5 8],而安慰剂负荷后则无变化。然而内皮细胞依赖的血管舒张和氧化状态无论在蛋氨酸负荷还是在安慰剂负荷前后均无变化。结论　轻中度同型半胱氨酸血症可导致人体血小板活性及内皮细胞功能的改变 ,提示同型半胱氨酸血症对动脉粥样硬化的发生、发展起重要作用。Objective To explore the effects of an acute elevation of plasma homocysteine levels on the endothelium, platelet activity and oxidative stress in normal Chinese subjects. Methods Acute hyperhomocysteinaemia was induced by methionine loading (100 mg/kg). Fifteen volunteers received either methionine or placebo in randomised order 7 days apart. Flow-mediated endothelium-dependent and endothelium-independent vasodilatation, markers of endothelial function, fibrinogen binding to platelets and platelet P-selectin expression, as well as plasma parameters of oxidative stress were examined at baseline and 4 hours after treatment. Results Plasma total homocysteine (tHcy) levels increased after methionine [(6.56±1.83) vs (15.2±3.01) μmol/l, P<0.001], but there was no change after placebo [(7.14±2.71) vs (6.75±2.30) μmol/L]. Compared with baseline, plasma von Willebrand factor, plasminogen activator inhibitor-1 levels and β-thromboglobulin increased after methionine [(68±33)% vs (86±13)%, P<0.05, (35±11) vs (69±38) ng/ml, P<0.05, (125±50) vs (78±50) U/ml, P=0.058,respectively], but did not after placebo. No changes were observed in endothelium-dependent vasodilatation and parameters of oxidative stress after placebo or methionine loading compared with baseline levels. Platelet fibrinogen binding and P-selectin expression were reduced 41% and 17%, respectively after placebo, but these reductions were attenuated after methionine loading. Conclusion Acute elevation of tHcy levels induced by methionine loading may promote platelet activity and impaire some aspects of endothelial function in healthy Chinese subjects.

关 键 词：同型半胱氨酸血症 血小板 内皮细胞 活性 体内研究 危险因子 心血管疾病 冠心病 

分 类 号：R541.4[医药卫生—心血管疾病]