肌醇脂质和cAMP在血小板活化因子诱导血小板聚集中的作用

目的：探讨肌醇脂质和cAMP两个细胞内第二信使系统在血小板活化因子(PAF)诱导血小板聚集过程中所起到的作用和相互关系。方法：采用PKC激动剂PMA和Ca^2 通道A23187,以及PKA激动剂Sp-cAMPS和抑制剂Rp-cAMPS干预的方法,分析观察这两个信使系统在PAF诱导血小板聚集过程中的作用;采用^3H—Inositol和^14C-Adenine双标记液体闪烁技术测定PAF诱导血小板可逆聚集过程中肌醇-1,4,5-三磷酸酯(IP3)和cAMP的水平变化的方法,分析研究这两个信使系统在PAF诱导血小板聚集过程中的相互关系。结果：(1)PMA和A23187能分别增强PAF的血小板聚集效应,而且两者具有协同作用;(2)Rp-cAMP和Sp-cAMPS两者本身都不能引起血小板聚集,但能分别增强和抑制PAF的聚集效应;(3)IP3和cAMP的水平变化分别与血小板的聚集和解聚过程一致。结论：(1)肌醇脂质信使系统是细胞内转导PAF诱导血小板聚集的主要胞内信使系统。(2)降低血小板内cAMP浓度不能诱导聚集,但能增强肌醇脂质信使系统的聚集效应;升高cAMP水平能拮抗肌醇脂质信使系统的作用,这可能是使可逆相聚集的血小板解聚的一个重要机制。     

Inhibition of platelet aggregation by monoclonal antibody reactive with beta 2-microglobulin chain of HLA complex

A mouse monoclonal antibody that reacts with beta 2-microglobulin, the light chain of class I major histocompatibility antigens, inhibited the second wave of human platelet aggregation induced by adenosine diphosphate and epinephrine and blocked aggregation and platelet protein phosphorylation induced by sodium arachidonate. Thrombin-induced platelet aggregation was inhibited at threshold concentrations but not at higher concentrations. The antibody also inhibited aggregation and secretion in response to thromboxane A2 or the stable endoperoxide analog, U46619. These results suggest that beta 2-microglobulin in the histocompatibility complex is intimately associated with transmission of the endoperoxide-thromboxane signal at the platelet membrane.     

双花提取物抗血小板聚集及抗凝血活性研究

[目的]研究玫瑰（Rosa rugosa）、月季（Rose chinensis Jacq.）双花提取物对血小板聚集及血液系统的作用。[方法]考察双花提取物对家兔全血凝血时间、体外血小板聚集率、凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）及大鼠纤溶系统的影响;采用高糖诱导人脐静脉内皮细胞损伤模型,考察其对细胞SOD活性和MDA含量的影响。[结果]双花提取物能抑制全血血小板聚集,延长全血凝血时间和APPT,缩短优球蛋白溶解时间（ECLA）,降低纤维蛋白原（FIB）含量。[结论]双花提取物具有抗血小板聚集及抗凝血活性。     

FGF-21对大鼠血小板聚集和活化的抑制作用

临床上大部分抗血小板药物存在继发性出血等副作用,亟需寻找一种安全有效的抗血小板药物。二磷酸腺苷(ADP)和花生四烯酸(AA)是介导血小板聚集的主要物质,文章探讨成纤维细胞生长因子-21(FGF-21)是否抑制ADP或AA诱导大鼠血小板聚集和活化。将大鼠分为正常对照组、正常鼠血小板活化组、阿司匹林干预后血小板活化组、FGF-21高、中、低剂量干预后血小板活化组。给药干预后提取各组血小板,分别用ADP或AA处理,观察处理后血小板聚集情况以及P选择素和血栓素(TXB2)表达水平。与正常对照组相比,正常鼠血小板经ADP或AA处理活化后,血小板聚集率显著升高,血浆中P选择素和TXB2含量明显上升;与正常鼠血小板经ADP或AA处理活化后相比,经阿司匹林和FGF-21干预后分别经ADP或AA处理活化后的血小板聚集率显著下降,血浆中P选择素和TXB2含量显著下降;FGF-21干预组经ADP或AA活化后,血小板聚集率、P选择素和TXB2含量下降水平呈明显剂量依赖性。目前国内外尚未发现FGF-21对血小板聚集与活化作用的相关报道,研究首次证明FGF-21具有抑制ADP和AA诱导血小板聚集和活化作用及明显的抗血凝作用,填补FGF-21在抗血凝研究领域空白,为开发安全有效的抗血凝药物提供理论依据。     

Histamine is an intracellular messenger mediating platelet aggregation

Inhibition of human platelet aggregation by N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine-HCl (DPPE), a novel antagonist of histamine binding, suggested that histamine might serve a critical role in cell function. Phorbol-12-myristate-13-acetate (PMA) or collagen was found to increase platelet histamine content in parallel with promotion of aggregation. Inhibitors of histidine decarboxylase (HDC) suppressed both aggregation and the elevation of histamine content, whereas DPPE inhibited aggregation only. In saponin-permeabilized platelets, added histamine reversed the inhibition by DPPE or HDC inhibitors on aggregation induced by PMA or collagen. The results indicate a role for histamine as an intracellular messenger, which in platelets promotes aggregation.     

Effects of housing conditions on homeostasis and blood rheological properties of lactating cows

The effects of the tie-stall and free-stall housing systems on homeostasis and blood rheological properties in the Black-and-White cows in the first half of lactation have been evaluated. One hundred and ninety five healthy third- and fourth-calved cows were analyzed. The erythrocyte parameters of hemostasis, blood viscosity, aggregation, and deformability were assessed. The free-stall housing system for cows has resulted in a significant decrease in the platelet aggregation (by 10.4 and 9.9% for spontaneous and induced platelet aggregation, respectively) along with weakening of the plasma cell adhesion in hemostasis (INR and APTT increased by 6.9 and 23.9%, respectively). A reduction in the blood viscosity value and the erythrocyteaggregation index by 4.9% with a 2.7% increase in their deformability index was revealed. The tie-stall housing system for cows has contributed to the extent of the platelet aggregation (by 15.5 and 34.2% for spontaneous and induced platelet aggregation, respectively) and the activation of hemocoagulation (decreases in INR and APTT by 4.6 and 16.3%, respectively). The obtained results have proven the negative effects of the tie-stall housing system on the recorded rheological properties of blood.     

Ultraviolet light: a new stimulus for the induction of platelet aggregation

Exposure to ultraviolet light (253.7 nanometers) causes mammalian blood platelets to aggregate. Aggregation is markedly enhanced in the presence of extracellular fibrinogen and is followed by the grodual of relatively small amounts of nucleotide and serotonin. Aggregation is inhibited by ethylenediamine tetraacetic acid or a combination of 2-deoxy-D-glucose and antimycin A. Adenosine, apyrase, and prostaglandin E(1) produced slight inhibition. The effect of exposure to ultraviolet light is cumulative and lasting. This agent may be used to study the process of platelet aggregation after the removal of the stimulus, by delaying the addition of fibrinogen until after cessation of irradiation. Thus ultraviolet light is the first agent known which may be used to study platelet aggregation in a period following its removal.     

Acetylenic analog of arachidonate that acts like aspirin on platelets

Development of irreversible platelet aggregation and the accompanying release of platelet-bound serotonin and production of prostaglandins is suppressed by 5,8,11,14-eicosatetraynoic acid (TYA). These findings may be explained by an ability of TYA to inhibit the enzymatic conversion of arachidonate to a newly recognized factor, labile aggregation-stimulating substance, which induces platelet aggregation, and to prostaglandins E(2) and F(2alpha).     

兔胚胎释放物对去脾小鼠血小板数量的影响

兔2细胞期或8～16细胞期胚胎培养液立即或经冷冻、鲜冻后注入去脾小鼠体内,能异源性引起去脾小鼠血小板数量显著减少(P<0.050)。血小板激活因子受体竞争性拮抗剂海风藤酮能抑制这种作用。试验说明兔胚胎释放血小板激活因子,并引起去脾小鼠血小板的聚集。     

Collagen-induced platelet aggregation: involement of an active glycopeptide fragment (alpha1-CB5)

It is widely held that the tertiary structure of collagen is essential for induction of platelet aggregation. However, we have found that the purified alpha1 chain prepared from denatured chick skin collagen aggregates platelets. This activity appears to be confined to a distinct region of the molecule representing less than 4 percent of the length of the alpha1 chain. Of all of the cyanogen bromide peptides of the alpha1 chain tested, only one (alpha1-CB5) was active. This glycopeptide, devoid of any ordered tertiary structure, contains only 36 amino acids and one residue of O-alpha-D-glucopyranosyl-(1 --> 2)-O-beta-D-galactopyranosyloxy-(1 --> 5)-lysine (Glc-Gal-Hyl). Blocking experiments strongly suggest that the Glc-Gal-Hyl is one of the structural determinants involved in collagen-induced platelet aggregation.     

大蒜有机硫化物抗肿瘤机制及应用前景探讨

大蒜为百合科葱属植物蒜的鳞茎,性温,味辣,其主要生物活性成分为多种有机硫化物（OSCs）,具备抗菌消炎、降低胆固醇、抗血小板聚集、抗肿瘤等功效。近年来国内外流行病学调查及试验研究表明,OSCs对多种恶性肿瘤均有明显的抑制作用,其主要作用机制包括预防致癌物质活化、调控细胞内酶系统进行解毒、阻断肿瘤细胞周期、诱导凋亡、抑制转移及抗肿瘤血管生成等。笔者就大蒜有机硫化物（OSCs）抗肿瘤作用机制进行概述,为临床开发低毒高效的抗肿瘤中药提供了依据。     

用分光光度计测血小板的聚集性

利用分光光度计测定了赖氨酸、P-转移因子、孕酮、Bio-plus等几种生物及非生物制剂在不同浓度下几种动物的PRP聚集率变化规律及影响。     

Crystal structure of the GpIbalpha-thrombin complex essential for platelet aggregation

Direct interaction between platelet receptor glycoprotein Ibalpha (GpIbalpha) and thrombin is required for platelet aggregation and activation at sites of vascular injury. Abnormal GpIbalpha-thrombin binding is associated with many pathological conditions,including occlusive arterial thrombosis and bleeding disorders. The crystal structure of the GpIbalpha-thrombin complex at 2.6 angstrom resolution reveals simultaneous interactions of GpIbalpha with exosite I of one thrombin molecule,and with exosite II of a second thrombin molecule. In the crystal lattice,the periodic arrangement of GpIbalpha-thrombin complexes mirrors a scaffold that could serve as a driving force for tight platelet adhesion. The details of these interactions reconcile GpIbalpha-thrombin binding modes that are presently controversial,highlighting two distinct interfaces that are potential targets for development of novel antithrombotic drugs.     

Platelet thromboxane synthetase inhibitors with low doses of aspirin: possible resolution of the "aspirin dilemma"

Selective pharmacological inhibition of thromboxane A2 synthesis did not prevent arachidonate-induced aggregation of human platelets in vitro. Prevention was instead achieved by a combination of thromboxane A2 inhibitors with low concentrations of aspirin. The latter partially reduced the proaggregatory cyclooxygenase products that accumulated when thromboxane A2 synthesis was blocked. The aspirin concentrations did not affect per se either platelet aggregation or prostacyclin synthesis in cultured human endothelial cells. The combination of thromboxane synthetase inhibitors with low doses of aspirin may offer greater antithrombotic potential than either drug alone.     

马苋菜对家兔血脂和血流变学的影响

本文报告了野生马苋菜对家兔血清总胆固醇 (TC)、甘油三酯 (TG)、低密度脂蛋白 (LDL -C)、高密度脂蛋白 (HDL -C)、血小板聚集率和红细胞变形指数的影响。每只家兔每日饲喂野生马苋菜 9g ,实验 8周。结果表明 :野生马苋菜明显降低血清TC、TG及LDL -C ,升高血清HDL -C ,而血小板聚集率和红细胞变形力作用也显著(p 0 0 5 )。说明野生马苋菜具有良好的预防和降低血脂及改善血液流变的功能 ,值得进一步研究和开发     

A heme export protein is required for red blood cell differentiation and iron homeostasis

Hemoproteins are critical for the function and integrity of aerobic cells. However, free heme is toxic. Therefore, cells must balance heme synthesis with its use. We previously demonstrated that the feline leukemia virus, subgroup C, receptor (FLVCR) exports cytoplasmic heme. Here, we show that FLVCR-null mice lack definitive erythropoiesis, have craniofacial and limb deformities resembling those of patients with Diamond-Blackfan anemia, and die in midgestation. Mice with FLVCR that is deleted neonatally develop a severe macrocytic anemia with proerythroblast maturation arrest, which suggests that erythroid precursors export excess heme to ensure survival. We further demonstrate that FLVCR mediates heme export from macrophages that ingest senescent red cells and regulates hepatic iron. Thus, the trafficking of heme, and not just elemental iron, facilitates erythropoiesis and systemic iron balance.     

Shunt bilirubin: evidence for two components

Studies with C(14)-labeled glycine and delta-aminolevulinic acid as heme-bilirubin precursors in man indicate that the early labeled or shunt bilirubin consists of two fractions. Fraction 1 requires 1 to 24 hours for maximum synthesis, is not dependent on marrow erythropoietic heme synthesis, and is possibly of anabolic origin (formed by a direct pathway from heme precursors). Fraction 2 requires 3 to 4 days for maximum production, is dependent on heme synthesis, and probably has its origin in the bone marrow, as a degradation product of red-cell heme.     

Thrombospondin promotes cell-substratum adhesion

The physiological role of the platelet-secreted protein thrombospondin (TSP) is poorly understood, although it has been postulated to be involved in platelet aggregation and cellular adhesion. In this report, TSP isolated from human platelets was found to promote, in vitro, the cell-substratum adhesion of a variety of cells, including platelets, melanoma cells, muscle cells, endothelial cells, fibroblasts, and epithelial cells. The adhesion-promoting activity of TSP was species independent, specific, and not due to contamination by fibronectin, vitronectin, laminin, or platelet factor 4. The cell surface receptor for TSP is protein in nature and appears distinct from that for fibronectin.     

Platelet-activating factor-induced aggregation of human platelets specifically inhibited by triazolobenzodiazepines

Platelet-activating factor (PAF), a naturally occurring phospholipid, is a potent activator of various biological processes, including platelet aggregation. The mechanisms by which PAF acts are largely unknown, partly because of the lack of specific inhibitors for PAF-elicited responses. It was found that in washed human platelets the psychotropic triazolobenzodiazepine drugs alprazolam and triazolam potently inhibited PAF-induced changes in shape, aggregation, and secretion. The effects were specific for PAF activation, since the responses of human platelets to adenosine diphosphate, thrombin, epinephrine, collagen, arachidonate, and the calcium ionophore A23187 were not inhibited by the triazolobenzodiazepines. These psychotropic drugs should be useful in investigating the possibility that PAF or PAF-like phospholipids play a role in neuronal function and in elucidating biochemical mechanisms activated specifically by PAF in a variety of cells.