血小板激活因子和银杏内酯B对洗涤兔血小板中cAMP含量的影响

研究了血小板激活因子(PAF)和PAF拮抗剂银杏内酯B对洗涤兔血小板中cAMP含量的作用. 结果表明PAF(0.1-1.0 μmol·L^-1)对血小板的基础cAMP水平无影响, 但对前列腺素E₁(PGE₁) 2 μmol·L^-1及4,5-二氢-6-［4-(1H-咪唑-1)苯基］-5-甲基-3-(2H)-哒嗪酮(CI-930) 20 μmol·L^-1引起的cAMP升高有显著的抑制作用. 银杏内酯B能完全拮抗PAF抑制PGE₁和CI-930升高cAMP的作用, IC₅₀分别为4.7和12.5 μmol·L^-1. 合用磷酸肌酸/磷酸肌酸激酶和阿司匹林对PAF和银杏内酯B的作用均无影响. 提示PAF对磷酸二酯酶的激活作用及腺苷酸环化酶的抑制作用是PAF的直接作用，与其同PAF受体结合有关.     

PAF受体拮抗剂的研究进展

目的综述血小板活化因子(platelet activating factor,PAF)受体拮抗剂的研究进展。方法根据已报道的介绍PAF及PAF受体拮抗剂的相关文献,将诸多PAF受体拮抗剂分为天然及合成2类,合成类再按结构分相关类别具体介绍。结果 PAF参与人体很多生理活动,异常途径生成的PAF会引起很多疾病的发生,归纳总结迄今为止研发的多种PAF受体拮抗剂。结论为PAF受体拮抗剂进一步的研究提供参考。     

自体动静脉内瘘反复功能丧失患者血小板功能分析

目的:探讨维持性血液透析患者自体动静脉内瘘反复功能丧失与血小板活化及聚集功能的关系。方法:选取我院血液净化中心以自体动静脉内瘘为血管通路的血液透析患者为研究对象,分为自体动静脉内瘘反复功能丧失组(A组,18例)和自体动静脉内瘘长期存活组(B组,30例)。另设健康对照组(C组,12例)。采用流式细胞仪测定各组血小板活化指标(CD62P,CD63)的表达,同时分别以腺苷二磷酸(ADP)和花生四烯酸(AA)为诱导剂,光学法检测血小板聚集率(PAgT),并进行组间比较。结果:与内瘘长期存活组及对照组相比,内瘘反复功能丧失组的血小板活化指标(CD62P和CD63)以及血小板聚集率(PAgTADP和PAgTAA)明显增高(P<0.05或P<0.01)。Logistic回归分析显示血小板CD62P表达增加及PAgTADP增高为自体动静脉内瘘反复功能丧失的危险因素。结论:维持性血液透析患者自体动静脉内瘘反复功能丧失与其循环的活化血小板水平增高及血小板聚集功能增强相关。     

粉防己碱对兔血小板聚集和血小板活化因子生成的影响(英文)

目的:探讨粉防己碱(Tet)对兔血小板聚集和PAF生成的影响.方法:卡西霉素(Cal)和PAF诱导血小板聚集的聚集率和Tet对血小板聚集的抑制率被测定;给予或未给予Tet处理之血小板用Cal刺激释放PAF的量也被测定.结果:在4—64 μmol·L~(-1)浓度范围,Tet明显抑制Cal和PAF诱导的血小板聚集.IC_(50)值分别为8.6μmol·L~(-1)和14.0μmol·L~(-1).Tet也浓度依赖性的抑制Cal诱导血小板释放PAF,IC_(50)值为21.0μmol·L~(-1).结论:Tet抑制血小板聚集作用与抑制内源性PAF生成有关.     

己酮可可碱减轻血小板激活因子致离体豚鼠肺通透性水肿(英文)

血小板激活因子(PAF,1 nmol·L~(-1))可使离体灌注豚鼠肺重量和微血管液体滤过系数明显增加,已酮可可碱(Pen,0.5和1.0mmol·L~(-1))对此有明显抑制作用,但对PAF引起的肺毛细血管压和静脉阻力的增高无明显影响。各组动物肺水肿的程度与灌注液中白细胞数无相关关系,提示Pen有直接抗肺血管通透性的作用。     

Effects of the PAF antagonists bepafant and L-659, 989 in endotoxic and septic shock

Many of the pathophysiological effects of endotoxin (ETX) can be mimicked by the administration of platelet activating factor (PAF), and the latter has been implicated as a possible mediator of the derangements seen in endotoxic shock. In this investigation, two new potent PAF antagonists, bepafant (WEB-2170) and L-659,989, were studied for their effects in experimental endotoxic and septic shock in rats. Pretreatment with the PAF antagonists, 15 min prior to the iv administration of Escherichia coli endotoxin (ETX), was found to be highly effective in decreasing the mortality caused by the lipopolysaccharide. The antagonists were less effective in reducing mortality when given as post-treatment 15 min after ETX, and were ineffective when post-treatment was delayed until 30 min after ETX. Administration of ETX caused manifestations of disseminated intravascular coagulation (DIC), including thrombocytopenia, prolongation of prothrombin time (PT) and partial thromboplastin time (PTT), hypofibrinogenemia, elevation of serum fibrin(ogen) degradation products (FDP), and gastrointestinal hemorrhage. With the exception of the thrombocytopenia, the PAF antagonists reduced or abolished all of the hematological manifestations of DIC caused by ETX. Septic shock was produced by ligation and puncture of the cecum in rats. The PAF antagonists, given as two iv doses (an initial 2.0 mg/kg dose administered 1.5 or 2.5 h after cecal puncture and a second dose given 5 h later), significantly reduced the cumulative 24-h mortality. These results provide added evidence of the importance of PAF and DIC in the pathophysiology of ETX and suggest that PAF antagonists may be useful in the clinical management of septicemia/endotoxemia. © 1993 Wiley-Liss, Inc.     

血小板活化因子诱发豚鼠气道高反应性及阿魏酸钠对其的影响

正常豚鼠吸入血小板活化因子（ＰＡＦ）２４ｈ后气道对组胺引起的收缩反应性明显增高，支气管肺泡灌洗液中的嗜酸性白细胞计数明显增多。用兔抗豚鼠血小板血清选择性耗竭血小板，向气道内注入肝素，或用阿魏酸钠２５，５０和１００ｍｇ·ｋｇ－１，ｉｖ均可不同程度抑制ＰＡＦ诱发的气道高反应性和嗜酸性白细胞向肺内募集。     

Platelet-released ADP stabilizes PAF-induced rabbit platelet aggregation by stabilizing intracellular calcium

ＰｌａｔｅｌｅｔｒｅｌｅａｓｅｄＡＤＰｓｔａｂｉｌｉｚｅｓＰＡＦｉｎｄｕｃｅｄｒａｂｂｉｔｐｌａｔｅｌｅｔａｇｇｒｅｇａｔｉｏｎｂｙｓｔａｂｉｌｉｚｉｎｇｉｎｔｒａｃｅｌｕｌａｒｃａｌｃｉｕｍ１ＹＩＦｕＸｉａｎ，ＧＵＯＺｈａｏＧｕｉ２（Ｌａｂ...     

花椒油素对兔血小板聚集的影响

花椒油素（ｘａｎｔｈｏｘｙｌｉｎ，ＸＴ）是从大戟科植物乌桕［Ｓａｐｉｕｍｓｅｂｉｆｅｒｕｍ（Ｌ）Ｒｏｘｂ］根皮中提取的化合物，分子式Ｃ１０Ｈ１２Ｏ４，相对分子质量：１９６２１。乌桕是传统的中药材，乌桕根皮有利水消积，杀虫、解毒之功效，主治水肿，臌胀...     

大鼠急性脊髓损伤后血小板活化因子的变化及甲基强的松龙对其的影响

目的利用大鼠急性脊髓损伤（ASCI）模型探讨大剂量甲基强的松龙（MP）对脊髓神经组织中血小板活化因子（PAF）的影响。方法54只Wister大鼠分为3组：未损伤组（A组）6只,损伤后注射0．9％氯化钠溶液组（B组）24只,损伤后注射MP组（C组）24只。用Allen氏重物坠击法（WD）,以25g×10cm致伤力造成B脊髓损伤模型,C组分别于术后即刻经尾静脉按首次剂量30mg／kg注射MP,以后按5．4mg·kg^-1·h^-1,共23h,分4次静脉推注;B组在同时间点注入等量0．9％氯化钠溶液。分别于术后2、5、12、28d取血及3组损伤部位脊髓组织做PAF测定。结果脊髓受损后,血及损伤组织中PAF均明显增高（P〈0．05）,注射MP后,血清及受损脊髓组织中PAF含量均明显下降（P〈0．05）。结论大剂量MP可能通过抑制损伤脊髓组织中PAF的表达,来发挥其对受损脊髓神经细胞的保护作用。     

红花黄色素对培养人脐静脉血管内皮细胞作用的研究

目的　观察红花黄色素 (SY)对血管内皮细胞的毒性 ,探讨其对血小板活化因子 (PAF)损伤血管内皮细胞作用的影响。方法　将培养的人脐静脉血管内皮细胞 (HVEC)和EVC 30 4细胞系分别分为PAF、SY、SY +PAF、银杏内酯(ginkolide)和 ginkolide +PAF 5组 ,以光镜和结晶紫比色法观察细胞形态和生物活性变化。结果　HVEC与PAF(10 -11～ 10 -6mol·L-1)孵育 30min后 ,其形态由长梭状或多边形变为椭圆或圆形 ,细胞间隙加大 ,由紧密排列变为疏松的单个细胞 ;HVEC与SY +PAF孵育后 ,形态变化与PAF所致相似 ,生物活性亦见下降趋势 ;HVEC与SY (0 5 71g·L-1)孵育仅 30min即出现形态改变 ,生物活性也有下降趋势 ;EVC 30 4与SY(1 143g·L-1)培养 4h后可致形态改变和生物活性下降。结论　在培养条件下未见SY拮抗PAF损伤内皮细胞的作用 ,高浓度SY对内皮细胞有一定的毒性     

血小板激活因子刺激血小板在脑微血管内皮细胞上粘附及药物的阻断作用(英文)

目的:研究血小板激活因子(PAF)刺激脑微血管内皮细胞导致血小板在内皮细胞上粘附及WEB,DMPP和粉防己碱的抑制作用. 方法:用[~3H]腺嘌呤标记血小板探讨PAF导致血小板在脑微血管内皮细胞上粘附和药物的抑制作用. 结果:PAF 10—100 nmol L~(-1)显著增加血小板与脑微血管内皮细胞的粘附率,WEB,DMPP和粉防己碱抑制由PAF刺激而导致的血小板在脑微血管内皮细胞上的粘附. 结论:DMPP和粉防己碱能够抑制PAF对脑血管的损害作用.     

Correlation of platelet activating factor and age-related macular degeneration

Objective: To investigate the role of Platelet Activating Factor (PAF) in the pathogenesis and development of Age-Related Macular Degeneration (ARMD).

Research design and methods: Fifty six patients with ARMD (24 patients with dry ARMD and 32 patients with wet ARMD) and 25 age-matched control participants underwent ophthalmological examination, including visual acuity measurement and evaluation of the retina. The participants were classified into three groups according to their retinal status, based on indirect fundoscopy, Optical Coherence Tomography and fluorescein angiography findings. In order to evaluate the concentrations of PAF in serum, blood samples were collected from all participants and were analyzed with ELISA technique.

Results: The concentrations of PAF differed significantly according to macular lesions and were found to be lower in patients with ARMD than control participants.

Conclusions: PAF levels are decreased along with the severity of ARMD. Understanding the role of PAF in pathogenesis of ARMD could be the impetus for the development of new therapies field of treatment of ARMD or even other retinal diseases.     

WEB-2086 AND INDOMETHACIN DO NOT MODIFY BLOOD PRESSURE FALL ON UNCLIPPING HYPERTENSIVE RATS

1. Pretreatment with intravenous WEB-2086 (0.5 mg/ kg; an antagonist of the actions of platelet activating factor; PAF) with or without indomethacin (2 mg/ kg) failed to prevent or modify the fall in blood pressure following unclipping of the renal artery of anaesthetized two-kidney, one-clip hypertensive rats. 2. The same medications given to two other groups of rats 60 min after unclipping when the blood pressure had fallen to stable levels failed to reverse the fall. 3. Despite evidence that both prostanoids and PAF can be detected in increased amounts in renal venous blood after unclipping, they do not appear to mediate the reduction in blood pressure in this model of reversible hypertension.     

四氢吡喃类药物对血小板激活因子诱导的脑微血管平滑肌细胞DNA合成及增殖的拮抗作用

研究了血小板激活因子（ＰＡＦ）对兔血小板聚集，牛脑微血管平滑肌细胞ＤＮＡ合成及增殖的影响及四氢吡喃类药物ｔｒａｎｓ－２，６－ｂｉｓ－（３，４－ｄｉｍｅｔｈｏｘｙ－ｐｈｅｎｙｌ）－ｔｅｔｒａｈｙｄｒｏ－（４Ｈ）ｐｙｒａｎ（ＳＺ－１）和ｔｒａｎｓ－２－（３，４，５－ｔｒｉｍｅｔｈｏｘｙｐｈｅｎｙｌ）－６－（２，４－ｄｉｆｌｕｏ－ｒｏｐｈｅｎｙｌ）－ｔｅｔｒａｈｙｄｒｏ－（４Ｈ）ｐｙｒａｎ（ＤＦＴＭ）的拮抗作用．结果表明：ＰＡＦ强烈刺激兔血小板聚集，在１．９１μｍｏｌ·Ｌ－１时，刺激的百分率为７１．７％．ＳＺ－１和ＤＦＴＭ剂量依赖性地抑制ＰＡＦ刺激的兔血小板聚集，ＩＣ５０分别为０．３９和０．８４ｎｍｏｌ·Ｌ－１．ＰＡＦ还刺激牛脑微血管平滑肌细胞增殖，在０．１ｎｍｏｌ·Ｌ－１时作用４８ｈ达最大效应．ＳＺ－１和ＤＦＴＭ显著抑制血小板激活因子的上述作用，在１ｎｍｏｌ·Ｌ－１时抑制率分别为２５．９％和３０．７％．ＳＺ－１和ＤＦＴＭ还抑制ＰＡＦ刺激的牛脑微血管平滑肌细胞ＤＮＡ合成，在１ｎｍｏｌ·Ｌ－１时抑制率分别为２９．１％和２４．４％．实验结果表明：ＰＡＦ可能通过促进血小板聚集，刺激脑血管平滑肌细胞增殖及ＤＮＡ合成而参与?     

红花黄酮成分抑制血小板激活因子介导的血小板活化作用

目的　观察红花黄酮成分杨梅素(Myr)和山奈酚(Kae)对血小板激活因子(PAF)诱导的兔洗涤血小板聚集、5 HT释放及血小板内游离钙离子浓度升高的影响。方法　以比浊法测定家兔洗涤血小板(WRP)聚集,邻苯二甲醛(OPT)荧光法测定5-HT浓度,Fura-2荧光探针测定血小板内游离钙离子浓度。结果　Myr和Kae体外呈浓度依赖性地抑制PAF诱发的WRP聚集及5-HT释放。Myr抑制WRP聚集的IC₅₀ 为17.5 μmol·L^-1 ;抑制5-HT释放的IC₅₀ 为64.1μmol·L^-1 。Kae抑制聚集、释放作用的IC₅₀ 分别为73.7μmol·L^-1 和128μmol·L^-1 ;同时Myr和Kae均能明显抑制PAF引起的血小板内游离钙增高。结论　Myr和Kae可抑制PAF诱导的血小板活化作用     

WHOLE BLOOD AGGREGATION AND PLASMA LYSO-PAF RELATED TO SMOKING AND ATHEROSCLEROSIS

1. Aggregation of diluted whole blood (impedance method) and thromboxane B2 production during aggregation were measured in cigarette smokers and non-smokers, aged 41-68 years, with (n = 14) and without (n = 15) major symptomatic peripheral vascular disease. The plasma level of the lyso derivative of platelet activating factor (lyso-PAF) was also measured using a bioassay with 14C-serotonin labelled rabbit platelets, after extraction and acetylation to active PAF. 2. Aggregation to ADP and collagen was significantly less in non-smokers without vascular disease (n = 8) than in the other three groups (P less than 0.01; ANOVA). Thromboxane B2 production was not significantly different between the groups. There was no significant difference in plasma lyso-PAF between groups. No change was found in any variable after smokers smoked two cigarettes. 3. In these older age subjects, both vascular disease and the smoking habit were associated with greater whole blood aggregation. However, current smoking and the smoking of two cigarettes did not affect aggregation in subjects with vascular disease and plasma lyso-PAF levels were not consistently related to either smoking or vascular disease.     

杨梅素对血小板活化因子拮抗的作用

目的研究杨梅素对血小板活化因子（PAF）的拮抗作用。方法以放射配体结合试验观察［³H］PAF与家兔血小板受体特异性结合的作用；以分光光度法测定PAF诱发血小板粘附的强度；以Fura-2荧光分光光度法测定兔多形核白细胞（PMNs）内钙离子浓度。结果杨梅素可浓度依赖地抑制［³H］PAF与血小板受体的特异性结合，其IC₅₀分别为 34.8，85.7和118.6 μmol·L^-1；该药可明显抑制PAF诱发的血小板粘附及PMNs内游离钙浓度的升高，且呈明显的量效关系，其抑制血小板粘附的IC₅₀为 13.1 μmol·L^-1。结论杨梅素具有抗PAF作用，为一新的PAF受体拮抗剂。     

小剂量茶碱对支气管哮喘患者外周淋巴细胞PAF受体mRNA表达的影响

目的了解茶碱对支气管哮喘患者血小板活化因子（ＰＡＦ）受体ｍＲＮＡ表达的影响。方法采用逆转录多聚酶链反应（ＲＴ－ＰＣＲ）技术检测了支气管哮喘患者及健康成人外周淋巴细胞ＰＡＦ受体ｍＲＮＡ的表达水平，探讨了小剂量茶碱对哮喘患者外周淋巴细胞ＰＡＦ受体ｍＲＮＡ表达的影响。结果（１）被检测的２０例健康成人中只有８例其外周淋巴细胞ＰＡＦ受体的ｃＤＮＡ可被扩增出来，而被检测的２１例哮喘患者均可获得ｃＤＮＡ片断；（２）服用小剂量茶碱１ｗｋ后，哮喘患者ＰＡＦ受体ｍＲＮＡ表达量（以“闪烁计数ｍｉｎ－１”表示，下同）与给药前的表达量相比无明显变化（Ｐ＞０．０５），服用２ｗｋ后，哮喘患者ＰＡＦ受体ｍＲＮＡ表达量由给药前的８６４０８±７４６２减少至６８９２７±５８８６（Ｐ＜０．０５），服用３ｗｋ后减少至５６７２０±４８６６（与给药前比较，Ｐ＜０．０１），接近健康人的表达量４９６８８±５４３８。结论连续服用小剂量茶碱可抑制外周淋巴细胞ＰＡＦ受体ｍＲＮＡ的表达。     

Structure-activity relationship of lysophosphatidylcholines in HL-60 human leukemia cells

AIM: To explore the structure-activity relationship of lysophosphatidylcholine (LPC) and lysolipid molecules from a marine sponge and ladybirds. METHODS: We tested three synthetic LPCs and four natural lysolipids on Ca2 mobilization in HL-60 human leukemia cells. RESULTS: We observed lysolipid-mediated Ca2 mobilization. The activity was the same in both ester- and ether-linked lysolipids, and introduction of a double bond or methoxy group on the alkyl chain did not significantly modulate the activity. However, replacement of trimethylammonium moiety in the choline structure with ammonium moiety reduced the activity. Furthermore, change of the alkyl chain length influenced the Ca2 response. CONCLUSION: LPC-induced Ca2 mobilization might be dependent on the length of alkyl chain and the presence of choline moiety in HL-60 leukemia cells.