脑血管病患者血小板α颗粒膜蛋白140的变化及临床意义

采用免疫放射法测定了１１６例脑血管病患者血浆和血小板表面ＧＭＰ－１４０的变化。发现脑动脉硬化组、脑梗塞组和脑出血组血浆和血小板表面ＧＭＰ－１４０均高于正常对照组（Ｐ＜０．０１），且脑梗塞与脑出血急性期明显升高，恢复期降至脑动脉硬化组水平。血小板表面与血浆内ＧＭＰ－１４０呈显著正相关（Ｐ＜０．０１）。结果表明脑血管病患者急性期血小板活性增高，血浆和血小板表面ＧＭＰ－１４０浓度可作为判断血小板活化和破坏程度的指标。     

高尿酸症合并高脂血症患者血小板活化功能的研究

目的对高尿酸患者、高血脂患者及高尿酸合并高血脂患者体内血小板的活化情况进行研究分析,了解患者血小板活化功能。方法对单纯性高尿酸血症患者(30例)、单纯性高脂血症(30例)及高尿酸血症并高脂血症患者(30例)3组人群进行血小板聚集率和血栓烷B2(TXB2)、血小板α颗粒膜蛋白140(GMP-140)活化因子水平的检测,与对照组(30例)进行比较。结果高尿酸组(A)、高血脂组(B)及高尿酸并高血脂组(C)3组的血小板最大聚集率(PAgT)明显高于对照组(P<0.05);血清中的TXB2、GMP-140也明显高于对照组(P<0.05),C组水平高于其他两组,且差异具有统计学意义(P<0.05)。结论高尿酸、高血脂对血小板的功能改变关系密切,血小板存在活化现象。在高尿酸并高血脂的患者中,血小板活化更为明显。     

缺血性脑血管病患者血浆D－二聚体和GMP－140含量的变化及临床意义

用ＥＬＩＳＡ双抗体夹心法和放射免疫法对７３例缺血性脑血管病患者血浆Ｄ－二聚体、血小板表面及血浆ＧＭＰ－１４０含量进行了测定。结果显示脑血栓形成（ＣＩ）急性期、恢复期和短暂性脑缺血发作（ＴＩＡ）患者血浆Ｄ－二聚体、血小板表面和血浆ＧＭＰ－１４０的含量均明显高于正常对照组（Ｐ＜０．００１）。ＴＩＡ伴有梗塞灶者无论血浆Ｄ－二聚体的含量还是血小板表面和血浆ＧＭＰ－１４０含量均显著高于无梗塞灶者（Ｐ＜０．０５，Ｐ＜０．００１，Ｐ＜０．０５）。结果提示缺血性脑血管病患者体内血液凝固性增强和血小板活化亢进。不仅对进一步了解缺血性脑血管病的发病机理和治疗提供了理论根据，而且对于观察病情演变、判断预后均有重要的临床意义     

血小板激活在氧化应激诱发小鼠短暂性脑缺血发作中的作用和替罗非班的干预作用

目的:探讨氧化应激在小鼠短暂性脑缺血发作中的作用及其病理生理学机制。方法:采用尾静脉注射过氧化物加缺氧诱发的小鼠TIA模型,通过测定血清可溶性P-选择素水平的变化和小鼠症状的出现时间、模型评分,观察血小板激活和替罗非班的干预作用。结果:模型组血清可溶性P-选择素显著高于对照组,分别为(4.19±0.17)ng/ml和(0.82±0.07)ng/ml,替罗非班组与模型组比较无显著差异(P>0.05);替罗非班组小鼠症状的出现时间明显晚于模型组,分别为(4.95±1.19)d和(3.75±1.12)d;症状评分也低于模型组(P<0.05)。结论:氧化应激通过激活血小板,进而诱发微血栓的形成导致小鼠TIA发作;血小板活化后伴随的炎症反应可能也起了一定的作用。     

偏头痛与血小板功能关系的研究

偏头痛与血小板功能关系的研究宋玉强韩仲岩马淑芹作者单位：２６６００３青岛医学院附属医院神经科（宋玉强韩仲岩），核医学科（马淑芹）偏头痛的发病机理尚不清楚，许多研究证实偏头痛与血小板功能异常有密切关系。血小板α颗粒膜蛋白１４０（ｇｒａｎｕｌｅｍｅｍｂｒ...     

急性脑梗死血小板超微结构及其功能变化关系的研究

目的 探讨脑梗死急性期血小板超微结构改变与血小板功能变化的关系。方法 脑梗死急性期22例患者（13例做电镜）,对照组20例（8例做电镜）,采用透射电镜观察血小板超微结构,酶联免疫吸附竞争法测定血小板GMP－140、酶联免疫吸附双抗体夹心法测定血浆GMP－140的浓度。结果 发病后3d的血小板超微结构改变明显,表现为促足增多,血小板膜多处破裂,聚集融合成片;α颗粒明显减少;线粒体也显著减少、残留着肿胀、空泡化。脑梗死组血小板GMP－140、血浆GMP－140浓度较对照组非常显著升高（P＜0．001）,血小板粘附率、血小板聚集率较对照组显著升高（P＜0．05）。结论 脑梗死急性期血小板功能增强,伴有血小板膜破裂,α颗粒明显减少,线粒体肿胀、空泡化。在脑梗死发病机制中,血小板聚集可能是导致脑血管机械堵塞的主要原因。     

藻酸双酯钠对急性脑梗死患者血小板α颗粒膜蛋白的影响

目的 研究藻酸双酯钠对急性脑梗死患者血小板α颗粒膜蛋白的影响及临床疗效。方法 将急性脑梗死患者随机分藻酸双酯钠（PSS）、阿司匹林（ASA）与噻氯匹定（TP）3个治疗组，测量治疗前及治疗后3d、7d、14d的血小板α颗粒膜蛋白-140含量，并观察治疗前后临床神经功能状况。结果 3组治疗后3d、7d、14d血浆GMP-140水平较治疗前明显降低，PSS组患者的神经功能恢复优于ASA与TP组。结论 PSS具有抗血小板聚集作用，能有效改善急性脑梗死患者神经功能缺损症状，提高其日常生活能力。     

脑血管病患者血小板α颗粒膜蛋白—140的临床研究

采用放射免疫方法对４５例脑血管病患者血浆及血小板膜表面的ＧＭＰ－１４０进行测定。发现病人组血浆中ＧＭＰ－１４０均高于正常对照组。脑梗塞及脑出血急性期组血浆及血小板膜表面的ＧＭＰ－１４０均高于脑动脉硬化症组。恢复期上述数据逐渐下降，接近脑动脉硬化症组水平。     

藻酸双酯钠对急性脑梗死患者血小板α颗粒膜蛋白的影响

目的研究藻酸双酯钠对急性脑梗死患者血小板a颗粒膜蛋白的影响及临床疗效。方法将急性脑梗死患者随机分藻酸双酯钠(PSS)、阿司匹林(ASA)与噻氯匹定(TP)3个治疗组,测量治疗前及治疗后3d、7d、14d的血小板α颗粒膜蛋白-140含量,并观察治疗前后临床神经功能状况。结果3组治疗后3d、7d、14d血浆GMP-140水平较治疗前明显降低,PSS组患者的神经功能恢复优于ASA与TP组。结论PSS具有抗血小板聚集作用,能有效改善急性脑梗死患者神经功能缺损症状,提高其日常生活能力。     

脑梗死患者血小板活化程度与血清、血小板镁浓度的关系

目的 :探讨脑梗死患者血小板活化程度与血清、血小板镁浓度的关系及其临床意义。方法 :对 30例急性期脑梗死患者和 2 5例正常对照者 ,采用抗人活化型血小板表面 α-颗粒膜蛋白 -1 4 0 ( GMP-1 4 0 )特异性单克隆抗体 ,以放射免疫法测定血小板活化状态。采用火焰原子吸收法测定血清镁、血小板镁浓度。结果 :急性期脑梗死患者血小板表面 GMP-1 4 0含量高于对照组 ( P<0 .0 5)。而血清镁、血小板镁水平均低于对照组 ( P<0 .0 1 )。相关分析发现 ,血清镁、血小板镁浓度分别与血小板表面 GMP-1 4 0含量呈直线负相关 ( r=-0 .70 4和 r=-0 .84 3,P<0 .0 1 )。结论 :急性期脑梗死患者血小板活化程度增高可能与血清镁、血小板镁降低有关。提示急性期脑梗死补镁治疗有重要意义。     

血浆GMP－140在实验性急性兔脑缺血时的变迁

实验性脑缺血时血小板醣化蛋白（ＧＭＰ－１４０）比对照组有显著升高，随缺血时间延长，ＧＭＰ－１４０呈渐进性升高，至缺血２４ｈ有显著下降，但ＴＸＢ２仍然呈升高趋势；缺血急性期的神经元及微血管循环障碍的病理变化与ＧＭＰ－１４０的演变过程有相关性，随水肿及循环障碍改善，ＧＭＰ－１４０显著下降，而ＴＸＢ２２４ｈ后仍然呈增高改变。结果表明急性脑缺血时ＧＭＰ－１４０的升高原因仅可能与血小板激活后的分解有关。它的动态变化趋势与急性循环损害的相关性表明ＧＭＰ－１４０在内皮依赖性血管舒缩障碍中有一定的意义，而ＴＸＢ２则受血小板在内的多种因素影响。     

Inhibition of ethanol-induced platelet activation by agents that elevate cAMP

Ethanol activates phosphoinositide-specific phospholipase C in human platelets resulting in the mobilization of intracellular calcium and shape change (Arch. Biochem. Biophys. 260, 480–492, 1988). Preincubation of platelets with agents that increase levels of cAMP (i.e., forskolin,prostaeyclin) inhibited these responses to ethanol in a concentration- and time-dependent manner. The inhibitory effect was potentiated by the phoshpodiesterase inhibitor, isomethybutylxanthine. When added after ethanol, these agents also reversed platelet shape change and lowered cytosolic free calcium to basal levels. The results demonstrate a direct inhibitory effect of cAMP on the ethanol-induced activation of phospholipase C.     

Influence of a calcium dependent protease inhibitor on platelet activation and secretion

Continuous proteolysis resulting in consumption of major cytoskeletal proteins may be essential for platelet activation and aggregation. In this study we evaluated the effect of a known protease inhibitor, Leupeptin, on agonist induced platelet aggregation and secretion. Platelets exposed to 10 ugs/ml of Leupeptin did not aggregate in response to the action of thrombin (0.2u/ml). However, a concentration of Leupeptin as high as 250 ugs/ml did not prevent arachidonate induced aggregation and secretion. Leupeptin (100 ugs/ml) effectively blocked thrombin (0.2 u/ml) induced elevation of cytosolic calcium, but did not affect arachidonate induced elevation of platelet intracellular calcium levels. At a concentration of 100 ug/ml, Leupeptin effectively blocked thrombin (0.5u/ml) induced clot formation of platelet poor plasma, suggesting that it can exert its effect on thrombin by preventing fibrinogen degradation. Effective K_i for the competitive inhibition of thrombin induced hydrolysis of a chromogenic substrate, S2238, by Leupeptin was 2.4 uM. Leupeptin inhibition of platelet function was reversible by washing platelets free of the polypeptide. Results of our study demonstrate that Leupeptin inhibits thrombin induced platelet activation, probably by interfering with its proteolytic activity on the platelet surface membrane. However, inhibition of platelet surface membrane associated proteases did not prevent activation of platelets by other agonists.     

Thiolprotease inhibitor, EST, can inhibit thrombin-induced platelet activation

Participation of thiolprotease in platelet activation was investigated. When platelets were treated with EST (L- -epoxysuccinyl-leucylamide (3-methyl)butane-ethyl ester, a membrane-permeable thiolprotease inhibitor) for 30 min, thrombin-induced aggregation and secretion were inhibited, and remained so even when the platelets were washed and resuspended in EST-free medium after the pretreatment. The inhibitory action of EST on thrombin-induced platelet aggregation and secretion was both dose-dependent and incubation-time-dependent. The inhibitory action of EST on platelet aggregation and secretion was shown not only in response to thrombin but also to platelet activating factor (PAF). Pretreatment of platelets with 1 mM EST for 30 min inhibited the 65 % of calpain (thiolprotease) activity in platelets. The phosphorylation of 40 kDa and 20 kDa proteins of platelets caused by stimulation with thrombin was blocked by the pretreatment with 1 mM EST. Phosphatidylinositol hydrolysis and inositol-1-phosphate production, which appear after stimulation of platelets with thrombin, were also inhibited by the pretreatment with 1 mM EST. The results suggest that EST was incorporated to inside of platelets, and inhibited activation of platelet through inhibition of thiolprotease.     

Lack of thrombopoietin potentiation of platelet collagen activation in the first trimester is associated with preeclampsia

To determine whether a difference exists in platelet reactivity to collagen and potentiation by thrombopoietin (TPO) between preeclamptic and non-preeclamptic patients, 187 first trimester pregnant patients were prospectively followed through pregnancy. Citrated blood, drawn at first (<14 weeks estimated gestational age) and third trimesters (>28 weeks), when patients were admitted for delivery, and 4-6 weeks postpartum, was assayed by a Whole Blood Impedance Aggregometer measuring platelet activation by 0.4 mug/ml collagen, +/-10 ng/ml TPO. There was no significant difference in 1st trimester platelet collagen activation by unpaired t-test between groups. Significant TPO potentiation of collagen activation (P<0.05, paired t-test) was observed in non-preeclamptic patients at the first and third trimesters. In contrast, preeclamptic patients' platelets show no significant (P>0.8, paired t-test) TPO potentiation at any time. While the mechanism for this difference in thrombopoietin potentiation of platelet activation by collagen as early as the first trimester is unknown, it may be one of the initiating events in this syndrome.