Dunbar J C, Reinholt L, Henry R L, Mammen E
Department of Physiology, Wayne State University, School of Medicine, Detroit, MI 48201.
Diabetes Res Clin Pract. 1990 Jul;9(3):265-72. doi: 10.1016/0168-8227(90)90055-x.
Alterations in platelet function have been observed in a number of diabetic states. Increased responsiveness to platelet-aggregating agents in diabetes associated with increased catecholamine production and/or turnover suggested that heightened sympathetic activity may contribute to this increased platelet aggregation response. To investigate this possibility, we made male Wistar-Furth rats diabetic with streptozotocin and treated them either with adrenergic inhibitors (clonidine, yohimbine, reserpine) or saline. After 2 weeks, arterial blood samples were collected in 3.8% sodium citrate or acid citrate dextrose (ACD). Platelet-rich plasma (PRP) was prepared, and platelet aggregation studies were conducted directly or conducted on washed platelets prepared from PRP collected with ACD. Platelet aggregation in response to ADP by PRP was reduced while the rate of disaggregation was increased in platelets from diabetic animals when compared to controls. However, platelet aggregation in response to ADP in washed platelets was increased in diabetic animals when compared to controls. Clonidine, reserpine and yohimbine significantly decreased the diabetes-induced increase in maximum aggregation. Thrombin-induced aggregation was not altered by diabetes or any of the treatments. The platelet size was increased in the diabetic animals and was decreased toward controls by clonidine, reserpine and yohimbine treatment. These studies suggest that diabetes increases platelet aggregation response in diabetic rats, and that blockage or suppression of adrenergic activity reverses or attenuates the diabetes-induced hypersensitivity to ADP.
在多种糖尿病状态下均观察到血小板功能的改变。糖尿病患者对血小板聚集剂的反应性增加，同时儿茶酚胺生成和/或周转率增加，这表明交感神经活动增强可能导致血小板聚集反应增加。为了研究这种可能性，我们用链脲佐菌素使雄性Wistar-Furth大鼠患糖尿病，并用肾上腺素能抑制剂（可乐定、育亨宾、利血平）或生理盐水对其进行治疗。2周后，采集动脉血样本于3.8%柠檬酸钠或枸橼酸葡萄糖（ACD）中。制备富含血小板血浆（PRP），并直接进行血小板聚集研究，或对用ACD采集的PRP制备的洗涤血小板进行研究。与对照组相比，糖尿病动物PRP对ADP的血小板聚集减少，而血小板解聚速率增加。然而，与对照组相比，糖尿病动物洗涤血小板对ADP的血小板聚集增加。可乐定、利血平和育亨宾显著降低糖尿病诱导的最大聚集增加。糖尿病或任何治疗均未改变凝血酶诱导的聚集。糖尿病动物的血小板大小增加，可乐定、利血平和育亨宾治疗后血小板大小向对照组降低。这些研究表明，糖尿病增加糖尿病大鼠的血小板聚集反应，肾上腺素能活性的阻断或抑制可逆转或减轻糖尿病诱导的对ADP的超敏反应。
