毛冬青甲素对血小板和血管内皮细胞功能的影响

毛冬青甲素对ADP及AA活化血小板功能的二条途径有抑制作用。本文证明毛冬青甲素对活化血小板的第三条途径TMVA也有抑制作用。提示毛冬青甲素为一广谱抗血小板药,并可抑制丙二醛的生成,但不具有刺激人工培养人脐静脉内皮细胞生成前列环素的能力。     

API0134对大鼠血浆和血小板血栓素B2生成与血小板聚集的影响

用放射免疫分析法和比浊法测定ＰＡＩ０１３４对大鼠血浆血栓素Ｂ２浓度，血小板ＴＸＢ２生成血小板聚集的影响。静脉注射ＡＰＩ０１３４７０ｍｇ或１００ｍｇ．ｋｇ显著降低血浆ＴＸＢ２浓度，其降低２率分别为３８．８％和５１．６％，ＡＰＩ０１３４明显抑制ＡＤＰ诱导的大鼠血小板聚集和ＴＸＢ２生成，抑制率分别为２７．８％，３９．５％，和４１．４％，５３．６％，两抑制率间呈显著正相关。     

实验性低氧性肺动脉高压(猪)模型的血浆中血栓素A_2,前列环素和5-羟色胺的变化

本文报告九只猪在实验性低氧性肺动脉高压时,动静脉中的血栓素A_2的稳定代谢产物血栓素B_2(TXB_2),前列环素的稳定代谢产物6-酮-前列腺素F_(1α)(6-Keto-PGF_(1α))和5-羟色胺(5HT)的变化。结果发现在低氧前后及低氧加克甫定(硫甲丙脯酸,captopril)注射时,动脉血中TXB_2/PGF_(1α)比例显著升高(P<0.01),动脉中的5HT亦升高(P<0.05)。提示TXA_2/PGI_2的比例升高可能对低氧肺动脉高压有一定的作用。     

脑益嗪抗运动病时大鼠血浆PG和小脑Na~ K~ ATPase图像分析定量研究

为探讨脑益嗪抗运动病作用机理，采用放射免疫方法和计算机图像分析系统，对运动病组（ＭＳＧ）和脑益嗪药物预防组（ＣＰＧ）大鼠血浆ＴＸＢ２、６ＫｅｔｏＰＧＦ１α和小脑毛细血管内皮细胞Ｎａ＋Ｋ＋ＡＴＰａｓｅ进行定量测量和分析研究。结果表明ＣＰＧ大鼠血浆ＴＸＢ２和６ＫｅｔｏＰＧＦ１α显著低于ＭＳＧ（ｐ＜００５），而小脑毛细血管内皮细胞Ｎａ＋Ｋ＋ＡＴＰａｓｅ活性则明显高于ＭＳＧ（ｐ＜００１）。作者认为，血浆ＴＸＢ２和６ＫｅｔｏＰＧＦ１α降低，与脑益嗪阻断血小板和血管内皮细胞Ｃａ２＋内流有关。脑内Ｎａ＋Ｋ＋ＡＴＰａｓｅ活性升高，可能是因为脑益嗪扩张脑血管、增加脑血流，阻滞Ｃａ２＋内流的结果。这些变化可视为脑益嗪抗运动病作用的重要机理。     

血栓素A_2和前列腺环素与自发性高血压大鼠高血压发展的关系

本文观察了SHR和WKY及不同年龄SHR动脉血浆中TXA_2和PGI_2的稳定代谢产物TXB_2和6-Keto-PGF_(1α)的浓度及其比值变化。结果表明,SHR血浆中的TXB_2浓度显著高于WKY,对照组与实验组相比(207.1±59.8比1217.9±298.5P8/ml,P<0.001),而血浆中6-Keto-PGF_(1α)浓度,除高年龄组SHR外,其他各组均无明显改变;SHR各组血浆中6-Keto/TXB_2比值均显著低于WKY组,不同年龄组SHR血浆中TXB_2浓度相比,高年龄组明显高于低年龄组(2184.5±273.1比1290.6±284.4pg/ml,P<0.001),高年龄组血浆中6-Keto-PGF_(1α)浓度虽有升高,但6-Keto/TXB_2比值仍明显低于对照组(0.21±0.12比1.48±0.78,P<0.001)。这些变化可能与SHR高血压的持续发展有关。     

瓜蒌和心得安对家兔急性心肌梗塞后血小板聚集性及PGI_2-TXA_2平衡的影响

本文观察家兔AMI后冠状窦与动脉血中血小板聚集性和PGI_2与TXA_2的稳定代谢产物6-keto-PGF_(1α)与TXB_2血浆浓度的变化,以及瓜蒌注射液和心得安单独或联合治疗对其变化及梗塞范围的影响。结果表明结扎冠状动脉左室支6h,血小板最大聚集率,最大聚集速度及TXB_2均明显升高,且冠状窦与动脉血变化一致;6-keto-PGF_(1α)及6-keto-PGF_(1α)/TXB_2比值变化不明显。瓜蒌和心得安单独或联合用药,明显抑制血小板聚集和TXB_2的变化,并能显著缩小梗塞范围,但两药无协同作用。     

槲皮素磷酸钾对大鼠脑血栓形成模型血小板聚集及血浆TXB_2和6-keto-PGF_(12)水平的影响

以大鼠脑血栓形成为模型,观察槲皮素磷酯钾对大鼠脑血栓形成术24h后血小板聚集、血浆TxB2和6-keto-PGF12水平的影响,以及脑电图、脑重量和病理组织学改变。结果表明:复合血栓诱导剂1ml kg-1经颈内动脉注射能诱发大鼠同侧大脑半球内血栓形成,槲皮素磷酯酶钾10-20 mg kg-1能对抗大鼠脑血栓形成,降低体内血小板自发性聚集,抑制血浆TxB2的升高。提示槲皮素磷酸酯钾可能通过其抗血小板聚集及影响花生回烯酸代谢而发挥抗脑血栓形成作用。     

新生儿缺氧缺血性脑病患者血浆ET、TXA2和PGI2测定的临床意义

目的：探讨血浆内皮素（ET）、血栓素A2（TXA2）、前列环素（PG I2）在新生儿缺氧缺血性脑病发病中的作用。方法：应用放射免疫分析测定了33例缺氧缺血性脑病新生儿和30例正常新生儿血浆ET、TXB2、6-keto-PGF1α的含量。结果：缺氧缺血性脑病新生儿血浆ET、TXB2水平非常显著地高于正常新生儿组（P〈0.01）,而6-keto-PGF1α水平则显著地低于正常新生儿组（P〈0.01）;血浆ET水平与TXB2成正相关（r=0.6128,P〈0.01）,与6-keto-PGF1α水平负相关（r=-0.5011,P〈0.01）。结论：缺氧缺血性脑病新生儿血管内皮细胞存在内分泌功能紊乱、内皮素（ET）合成释放增加、前列环素（PG I2）水平降低、两者反馈调控失衡及ET与血栓素A2（TXA2）的协同作用在新生儿缺氧缺血性脑病的发病中具有重要的临床价值。     

Altered Endothelin-1 Signaling in Production of Thromboxane A2 in Kupffer Cells from Bile Duct Ligated Rats

Kupffer cells (KCs), the liver resident macrophages accounting for 80–90% of the total population of fixed tissue macrophages in the body, not only play a key role in host defense via removing particulate materials from the portal circulation, but may also contribute to the pathogenesis of various liver diseases. We have previously demonstrated that KCs play an important role in controlling portal hypertension and hepatocellular injury via releasing thromboxane A₂ (TXA₂) in early fibrosis induced by one-week bile duct ligation (BDL). Production of TXA₂ is controlled by cytosolic phospholipase A₂ (cPLA₂) that is activated by the interaction of entothelin-1 (ET-1) with its G-protein coupled ET receptor B (ETBR). However, the signaling pathways that contribute to the ET-1-induced activation of cPLA₂ and production of TXA₂ in KCs in the normal healthy or injured livers are not yet clear, which are investigated in the present study using isolated KCs from one-week BDL or sham rats. The pharmacological inhibition of cPLA₂ or chelation of intracellular calcium abrogated the ET-1 induction of TXA₂ from KCs. Compared to those from sham rats, KCs from BDL animals displayed a significantly enhanced responsiveness of p38 MAPK to ET-1, increased ETBR and Gαi subunit but decreased Gαq and Gα11 expression. Inhibition of ERK1/2 or Gq signaling abrogated significantly the ET-1 induction of TXA₂ in sham KCs but only slightly in BDL KCs. In contrast, inhibition of p38 MAPK and Gi signaling markedly attenuated the ET-1 induction of TXA₂ in BDL KCs but had no effect in sham KCs. Lastly, inhibition of PLC or PKC abrogated ET-1 induction of TXA₂ in KCs from both sham and BDL groups. The hepatic stress (such as BDL) induces significant modifications in the receptor and intermediates of ET-1 signaling in KC and subsequently alters ET-1 signaling mechanisms, particularly a shift from Gq induced signaling to Gi induced signaling, in the activation of cPLA₂ and production of TXA₂ in response to ET-1.     

人参总皂甙对血栓素A_2和前列环素样物质平衡的调节

人参是传统的名贵中药,用于多种疾患的治疗;对实验性血栓确有预防作用。人参总皂甙(ginseng saponins,简称GS)是人参的主要有效成份,具有人参的多种生理功能。药理实验证明,GS能预防动脉粥样硬化,缩小家兔实验性心肌梗塞范围,抗实     

Thromboxane production and platelet aggregation in type 2 diabetes mellitus without vascular complications

Summary Diabetic individuals frequently have platelet hyperaggregability and increased thromboxane (TXB₂) production. To evaluate whether improvement of metabolic control or changes in fatty acid composition of serum lipids might alter thromboxane (TXB₂) formation and platelet function, we followed up 25 newly diagnosed type 2 diabetics without angiopathy for about 6 months. Improvement of metabolic control (HbA₁, fell from 12.0±0.3 to 9.0±0.3%;p<0.01) was associated with significant decrease in total cholesterol, triglycerides, and ratios of total cholesterol/HDL-cholesterol and LDL-cholesterol/HDL-cholesterol. Palmitic acid of phospholipids decreased significantly, whereas eicosapentaenoic acid increased. Regardless of this, the ADP-induced platelet aggregability and sensitivity were not altered. There was no effect whatever on the TXB₂ synthesis capacity of clotting whole blood (204.9±25.0 vs 222.8±32.0 ng/ml) over 6 months of treatment. Platelet aggregability and TXB₂ formation were not correlated to the degree of metabolic control, nor were there any correlations to serum lipids and their fatty acid composition. Thus, we are tempted to speculate that glucose metabolism in diabetes itself does not affect platelet aggregation or TXB₂ formation in type 2 diabetes mellitus.Abbreviations TXB₂ Thromboxane B₂ - HbA₁ Glycosylated hemoglobin A₁ - HDL High density lipoproteins - LDL Low density lipoproteins - ADP Adenosine diphosphate - P/S Ratio Polyunsaturated fatty acids/saturated fatty acids ratio - ECG Electrocorticogram - TAC 50 Threshold aggregating concentration eliciting 50% of maximal response Presented in part at the 23rd Annual Meeting of the European Society for Clinical Investigation, April 19–22 1989, Athens, Greece.     

三种莨菪药对急性肾衰大鼠血栓素及前列环素代谢的影响

本文研究了急性肾衰时血栓素及前列环素代谢的改变，观察了樟柳碱，东莨菪碱及山莨菪碱对这些改变的影响。结果表明，肾衰后24小时，左肾皮质及髓质血栓素B2（TXB2）及6－酮－前列腺素F1α（6KF）均明显增高，6KF与TXB2比值无明显改变；肾衰后48小时，左肾皮质及髓质TXB2明显增高，6KF增高不明显，6KF与TXB2比值明显降低。三种药物对肾组织TXB2及6KF无明显影响．但均可提高血液中6KF含量，使6KF与TXB2比例增加。其作用以东莨菪碱最明显，其次是樟柳碱及山莨菪碱。结果说明，肾组织TXB2和6KF比例的变化可能是急性肾衰维持期肾组织血流量持续降低，肾功能恶化的重要因素。东莨菪碱及樟柳碱可提高血液中前列环素含量，这可能有助于肾组织血流量的恢复。     

流体剪应力作用下VWF-A1A2A3介导的血小板P-选择素的原位表达

目的探讨流体剪应力(fluid shear stress,FSS)对VWF-A1A2A3介导的血小板表面P-选择素表达的影响。方法利用平行平板流动腔实验系统,以CD62P:FITC作为血小板表面P-选择素表达的指示剂,采用荧光显微镜观察分析在不同FSS条件(0、1、2 Pa)下,血小板经由VWF-A1A2A3特异介导黏附后P-选择素表达随时间的变化过程,提取特征参数。结果 FSS扣动了血小板激活并产生P-选择素表达的扳机,激活比率受FSS大小和持续时间的正向调节,在1 Pa和2 Pa时的最高激活比率分别为9.42%和14.59%;P-选择素表达水平随FSS作用时间的延长先提高后降低,呈现一个"双相"的变化过程,最佳作用时间为7.5 min;P-选择素表达的荧光峰值随剪应力的增加而上升。结论血小板P-选择素表达受FSS和VWF-A1A2A3的协同调控,表达水平与力信号的持续时间相关。     

活血通脉汤对脑缺血再灌注损伤大鼠血浆TXB2、6-keto-PGF1α的影响

目的探讨活血通脉汤对脑缺血再灌注损伤大鼠血浆血栓素B2(TXB2)、6-酮前列环素F1α(6-keto-PGF1α)的影响。方法制作脑缺血再灌注模型,70只大鼠随机平均分为活血通脉汤组、阿司匹林阳性对照组、手术组和假手术组,应用放免法分别测定缺血再灌注24、48 h血浆TXB2、6-keto-PGF1α及其比值。结果手术组大鼠脑缺血再灌注24、48h血浆TXB2水平明显高于假手术对照组(P<0.01),6-keto-PGF1α显著低于假手术对照组(P<0.01),血浆TXB2/6-keto-PGF1α比值增加(P<0.01),缺血再灌注24、48 h脑组织缺血范围显著大于假手术对照组(P<0.01)。使用活血通脉汤治疗能降低TXB2水平,升高6-keto-PGF1α水平,使血浆TXB2/6-keto-PGF1α比值保持在正常水平,减少缺血脑组织范围。结论活血通脉汤可纠正脑缺血再灌注后循环血中TXB2/6-keto-PGF1α的平衡失调及降低脑组织缺血程度,减轻脑缺血再灌注损伤。     

Ang-(1-7)对实验性高血压大鼠血压的影响及其机制的初步研究

目的观察Ang-(1-7)对二肾一夹(2K1C)高血压大鼠血压的影响,并探讨其机制.方法采用微渗泵植入技术,建立Ang-(1-7)对高血压大鼠干预模型,用大鼠电脑血压心率仪记录大鼠无创血压,八导生理记录仪有创血压,酶法检测血浆一氧化氮(NO),放免法检测血浆6-酮-前列腺素F1α、心钠素(ANP).结果Ang-(1-7)能有效降低2K1C大鼠形成中的和已形成的高血压,升高血浆一氧化氮(NO),PGI2、心钠素(ANP).结论Ang-(1-7)对2K1C大鼠高血压具有一定的预防及治疗作用,升高血浆NO,PGI2、ANP是其机制之一.     

西红花提取物对大鼠血小板聚集、软脑膜血流量和离体兔主动脉条的作用

经实验证明西红花提取物ＸＨＨ－１的小鼠灌胃ＬＤ５０大于１０ｇ／ｋｇ，毒性很小。ＸＨＨ－１的五个浓度（０．５、１、２、３、４ｍｇ／ｍｌＰＲＰ）均能显著地对抗由ＡＤＰ引起的大鼠体外血小板聚集，并缩短血小板最大聚集时间。ＸＨＨ－１浓度为４、８、１２ｍｇ／ｍｌ时，对ＫＣｌ引起的离体兔主动脉血管平滑肌的抑制作用与对照组相比都有非常显著的统计学意义。大鼠静注１０ｍｇ／ｋｇＸＨＨ－１后１０ｍｉｎ，软脑膜血流量增加５４％，２０ｍｉｎ时仍维持在相近水平，灌胃给药２５０ｍｇ／ｋｇ后３０ｍｉｎ。软脑膜血流量同给药前相比增加了３９％，至６０ｍｉｎ仍维持这一水平，均有显著统计学差异。     

肝硬化患者血浆PGI2和TXA2含量变化的临床意义

目的:观察肝硬化患者血浆中前列环素（PGI₂）和血栓素A₂（TXA₂）含量的变化,探讨其在肝病发生、发展中的临床意义。方法:选取2010年10月～2011年10月间云南省第三人民医院消化内科收治的肝硬化患者48例及健康体检正常者30例,采用放射免疫分析（RIA）分别测定其血浆中PGI₂和TXA₂的代谢产物6-酮-前列环素(6-Keto-PGF_1α)和血栓素B₂（TXB₂）的含量,进行统计学分析。结果:Child-Pugh分级A级患者血浆中6-Keto-PGF_1α和TXB₂含量分别为（108.8±34.2）ng/L和（87.5±19.3）ng/L,B级为（139.4±38.3）ng/L和（106.6±20.7）ng/L,C级为（181.9±53.2）ng/L和（128.5±26.3）ng/L,正常对照组为（90.6±23.6）ng/L和（73.6±18.3）ng/L,经方差分析,各组之间差异有统计学意义（F值分别为5.12,4.63,P均<0.01）;各组间经SNK-q检验比较,差异均有统计学意义（P均<0.01）;血浆中6-Keto-PGF_1α和TXB₂含量在Child-Pugh分级A、B、C级患者中逐级增高。结论:血浆PGI₂和TXA₂参与了肝硬化的发生、发展,动态监测PGI₂和TXA₂含量的变化有利于肝硬化患者病情的判断。