糖尿病并发脑血管疾病时血小板活化标志的研究

Platelet Activation Markers in Diabetes Mellitus Patients Complicated with Cerebrovascular Disease

目的:血小板活化在糖尿病血管并发症的发病机制中起着重要的作用。本文研究哪些指标在实验诊断上更为敏感或更有价值。方法:对85例糖尿病患者(其中47例合并脑血管疾病,38例无血管并发症)与36名年龄匹配的健康人进行了研究。血浆血栓烷B_2(TXB_2)、11-去氢-血栓烷B_2(DH-TXB_2)与血浆P-选择素用免疫分析法测定。血小板膜糖蛋白(GP)与血小板纤维蛋白原结合能力用流式细胞仪和单克隆抗体测定。血小板膜表面P-选择素数量用免疫放射法(IRMA)测定。结果:并发脑血管疾病的糖尿病患者的血浆TXB_2和DH-TXB_2明显升高(P<0.01),后者增高的程度更大,与正常值很少重叠。血小板GPⅠb减少(P<0.05),GPⅡb和GPⅢa无改变,但GPⅡb-Ⅲa复合物增加(P<0.01)。血小板膜P-选择素与血小板纤维蛋白原结合量显著高于正常(P<0.001)。血小板表面P-选择索的数量以及血浆P-选择素水平也有增高(P<0.01)。另一方面,无血管并发症的糖尿病患者上述指标的改变与正常对照比较无统计学差异。结论:血浆DH-TXB_2、血小板纤维蛋白原结合量与血小板模P-选择素测定比其它指标更能反映出体内血小板的活化,具有更高的诊断敏感性。

Objective: Platelet activation plays an important role in the pathomechanism of vascular complications of diabetes mellitus (DM) . This study is to investigate which ones are more sensitive or more valuable for laboratory diagnosis of this situation. Methods: 85 DM patients (47 with cerebrovascular disease, 38 without vascular diseases) and 36 age-matched healthy individuals were enrolled into this study. Plasma thromboxane B2(TXB2), 11-dehydro-TXB2 (DH-TXB2 ) and P-selectin were measured using the method of immunoassay. Platelet membrane glycoproteins (GP) and fibrinogen-bincling to platelets were analyzed by using flow cytometry (FCM) and monoclonal antibodies (Mab). The number of P-selectin molecules on cell surface was calculated using radio-irnmunoassay (ERMA). Results: In DM patients who had cerebrovascular diseases, both plasma TXB2 and DH-TXB2 were markedly elevated (P<0.01), the latter was more increased and less overlapped with normal range. GP I b was decreased (P<0.05), GP Ⅱ band Ⅲ a were not altered, whike GP Ⅱ b-Ⅲa complex was increased (P<0.01). Platelet membrane P-selectin and fibrinogen-binding were much higher than those of normal subjects (P< 0.001). And platelet surface P-selectin number and plasma P-selectin were also increased (P<0.01). On the contrary, no statistically significant difference was found between DM patients who had no vascular events and normal controls in all these experimental indices. Conclusion: The measurement of plasma 11-dehydro-TXB2, and the determination of platelet fibrinogen binding and P-selectin expression would reveal a higher diagnostic sensitivity for detecting in vivo platelet activation than other markers.