不同剂量阿司匹林对冠心病患者血小板活性和数目的影响

为探讨阿司匹林对冠心病患者合适的治疗剂量，采用抗人血活性血小板α颗粒膜蛋白１４０（ＧＭＰ－１４０）特异单克隆抗体１２５Ｉ－ＳＺ－５１测定不稳定心绞痛患者，每日服用阿司匹林５０ｍｇ（２７例）、１５０ｍｇ（２６例）、３００ｍｇ（３０例）治疗前和治疗７天后三组血小板膜表面ＧＭＰ－１４０分子数，并常规计数血小板数目。结果显示阿司匹林治疗后血小板膜表面ＧＭＰ－１４０分子数明显降低，而血小板数目明显升高，并且随着阿司匹林剂量的增加，两者的变化程度也增大（Ｐ值均＜０．０１），当剂量达３００ｍｇ时，前者低于健康人组（Ｐ＜０．００５），后者已达健康人组水平（Ｐ＞０．０５）。三组阿司匹林剂量的近期副作用差别则无显著性。表明用该药治疗不稳定性心绞痛患者开始采用每日３００ｍｇ的剂量是合理的。     

阿司匹林对冠心病患者冠状循环血小板功能及前列腺素的影响

为研究阿司匹林对冠心病患者血小板及前列腺素作用，５３例受试对象分为服用小剂量阿司匹林（ＡＳＡ，５０ｍｇ／ｄ，２周以上）的冠心病组、未服ＡＳＡ的冠心病组及正常对照组。同时采集受试者升主动脉及冠状静脉窦血测定血浆及血清血栓素Ｂ＿２（ＴＸＢ＿２）及６－酮－前列腺素Ｆ＿（１α）（６－酮－ＰＧＦ＿（１α））的水平。结果提示，小剂量ＡＳＡ选择性地抑制冠心病患者体循环中ＴＸＡ＿２的生成及释放；ＡＳＡ对冠心病患者冠状循环中ＴＸＡ＿２及ＰＧＩ＿２的生成与释放表现出同等程度的抑制，而没有明显的选择性；ＡＳＡ不能完全抑制冠心病患者冠状循环中血小板的激活。     

血小板活化在运动所致心肌缺血中的临床意义

采用放射免疫法测定５５例冠心病患者和２０例健康人踏车试验（ＥＴ）前后血小板膜表面α－颗粒膜蛋白（ＧＭＰ－１４０）分子数和血浆血栓素Ｂ＿２（ＴＸＢ＿２）浓度变化。结果显示，冠心病组３６例ＥＴ阳性，１９例ＥＴ阴性，正常对照组２０例ＥＴ均阴性。冠心病ＥＴ阳性组运动后即刻血小板膜表面ＧＭＰ－１４０、血浆ＴＸＢ＿２较运动前明显升高（Ｐ＜０．０５）。冠心病ＥＴ阴性组和正常对照组运动前后血小板膜表面ＧＭＰ－１４０、血浆ＴＸＢ＿２差异无显著性（Ｐ＞０．０５）。提示血小板活化可能是运动所致心肌缺血的重要因素。     

AT1拮抗剂氯沙坦对原发性高血压患者前列环素及 …

目的：探讨氯沙坦对原发性高血压患者前列环素和内皮素的影响。方法 ６０例原发性高血压患者随机分成Ａ、Ｂ组（各３０例）,分别服氯沙坦５０～１００ｍｇ／ｄ和依那为利５～１０ｍｇ／ｄ,疗程６周。另选择２５例血压正常的志愿者或年度体检人员作为健康对照组,测服药前后动脉血压,用放射免疫法测血浆６酮－前列环素Ｆ１α（６－Ｋ－ＰＧＦ１α）、血栓素Ｂ２（ＴＸＢ２）、内皮素（ＥＴ）以及血管紧张系Ⅱ（ＡｎｇⅡ）水平。结     

老年肺心病伴MOF者血浆TXB_2、6－k－PGF_（1α）含量变化

选３５例健康老人为对照组（Ａ组），另选２５例老年肺心病急性发作期（Ｂ组）、２２例老年肺性脑病患者（Ｃ组）、２１例老年肺心病伴肾衰患者（Ｄ组），测定后３组血气显示，Ⅰ型呼衰２４例（Ｅ组），Ⅱ型呼衰３０例（Ｆ组）。测定这６组的血浆血栓素（ＴＸＢ２），６－酮前列环素（６－ｋ－ＰＧＦ１α）含量，结果显示Ｂ、Ｃ、Ｄ、Ｅ、Ｆ组的血浆ＴＸＢ２、６－ｋ－ＰＧＦ１α含量及ＴＸＢ２／６－ｋ－ＰＧＦ１α比值均高于Ａ组，以Ｄ组的值为最高，其升高值与病情加重程度相一致。提示血浆ＴＸＢ２含量升高，其ＴＸＢ２／６－ｋ－ＰＧＦ１α比值增大，可引起肺心病发作或肺心病伴多器官衰竭（ＭＯＦ）的发生。反之，肺心病可缓解。说明血浆ＴＸＢ２是肺心病发病中起着重要的病理介导作用。     

开博通在溶栓治疗中对血管内皮细胞功能的影响

为探讨开博通在急性心肌梗塞患者溶栓治疗过程中对血管内皮细胞功能的影响,观察了６８例发病后１２ｈ内入院的急性心肌梗塞（ＡＭＩ）患者,在溶栓治疗后随机分为开博通组和安慰剂组,开博通组在溶栓后立刻给予开博通,首剂６．２５ｍｇ／次,此后１２．５ｍｇ／次,２次／天;于口服开博通前即刻及之后第２４ｈ和４８ｈ测定内皮素（ＥＴ）、前列环素（ＰＧＩ２）的代谢产物６－酮－前列腺素－Ｆｌａ（６－Ｋｅｔｏ－ＰＧＦＩａ）和血栓素Ａ２（ＴＸＡ２）的代谢产物血栓素Ｂ２（ＴＸＢ２）的浓度,并计算６－Ｋｅｔｏ－ＰＧＦ１ａ／ＴＸＢ２的比值,设安慰剂组作为对照。结果发现开博通可明显降低未通患者ＥＴ浓度,而再通患者的ＥＴ水平不受影响,明显地降低ＴＸＢ２（Ｐ＜０．０５）的水平,轻度降低６－Ｋｅｔｏ－ＰＧＦ１ａ水平（Ｐ＞０．０５）,使６－Ｋｅｔｏ－ＰＧＦ１ａ／ＴＸＢ２（Ｋ／Ｔ）比值明显增高（Ｐ＜０．０５）。提示在ＡＭＩ患者溶栓治疗同时应用开博通,可纠正Ｋ／Ｔ比例失调,对ＡＭＩ产生治疗作用。     

盐酸黄连素与小剂量阿司匹林抗血小板聚集功能的对比研究

１２０例动脉硬化性脑梗塞患者分别服用盐酸黄连素（１２００ｍｇ／ｄ）的和阿司匹林（５０ｍｇ／ｄ），其抗血小板聚集作用有效率分别为９５．０％和９０．０％，使血小板最大聚集率下降幅度分别为３５．０３±１２．２６和３８．５２±１２．３７，二者比较无明显差异（Ｐ＞０．０５）。盐酸黄连素能使血小板内ＴＸＡ２含量显著降低（ＴＸＡ２途径）、ｃＡＭＰ含量显著增高，从而明显地抑制血小板激活因子ＰＡＦ（ＰＡＦ途径），而这是阿司匹林所缺乏的。显示了盐酸黄连素比阿司匹林更加优越的应用前景。     

高血压病合并高胰岛素血症患者血浆凝血■烷B_2及6－酮－前列腺素F_（1α）的变化

目的：研究血浆凝血烷Ｂ２（ＴＸＢ２，血栓素Ｂ２）及６－酮－前列腺素Ｆ１α（６－ｋｅｔｏ－ＰＧＦ１α）在原发性高血压（高血压病）伴高胰岛素血症患者中的变化。方法：对４０例高血压病伴高胰岛素血症患者及３０例正常人进行口服糖耐量、胰岛素释放水平测定，在糖耐量过程中进行血压、血浆ＴＸＢ２及６－ｋｅｔｏ－ＰＧＦ１α的观察。结果：与正常组比较，高血压病组基础及糖刺激后血浆胰岛素水平显著升高（Ｐ＜０．０５），ＴＸＢ２增高（Ｐ＜０．０１）及６－ｋｅｔｏ－ＰＧＦ１α水平显著下降（Ｐ＜０．０５）。结论：高血压合并高胰岛素血症时，血浆ＴＸＢ２增高、ＴＸＢ２／６－ｋｅｔｏ－ＰＧＦ１α比值升高在高血压的发生发展中起着重要作用。     

老龄大鼠脑缺血再灌注前列腺素和β-内啡肽的变化

目的 血栓素Ａ２（ＴＸＡ２）与前列环素（ＰＧＩ２）平衡失调和β－内啡肽（β－ＥＰ）的变化方面研究老龄大鼠脑缺血再灌注损伤的机制。方法 青年大鼠（５月龄）和老龄大鼠（２０月龄以上）均分为模型组和正常对照组，观察大鼠全脑缺血再灌注后ＴＸＡ２与ＰＧＩ２和β－ＥＰ含量。结果 青年对照组血浆血栓素Ｂ２（ＴＸＢ２）水平低于老年对照组和青年模型组。青年对照组血浆６－酮－前列腺素Ｆ１α（６－ｋｅｔｏ－ＰＧＦ１α）高于青年模型组，而低于老龄对照组；老龄模型组高于青年模型组。青年模型组血浆ＴＸＢ２／６－ｋｅｔｏ－ＰＧＦ１α高于青年对照组和老龄模型组。青年模型组脑组织ＴＸＢ２高于青年对照组，而低于老龄模型组。老龄对照组脑组织６－ｋｅｔｏ－ＰＧＦ１α高于青年对照组，老龄模型组高于青年模型组。老龄对照组脑组织ＴＸＢ２／６－ｋｅｔｏ－ＰＧ     

晚期血吸虫病患者血浆TXB2和6—keto—PGF1a测定及其意义

用放射免疫法测定３７例晚期血吸虫病（晚血）患者和３０例正常人血浆ＴＸＢ２、６－ｋｅｔｏ－ＰＧＦ１ａ。结果晚血患者ＴＸＢ２显著降低（Ｐ〈０．００１），而６－ｋｅｔｏ－ＰＧＦ１ａ，则显著增高（Ｐ〈０．００１）。其中晚血出血患者ＴＸＢ２、６－ｋｅｔｏ－ＰＧＦ１ａ的变化更显著。晚血患者平均动脉压（ＭＡＰ）显著低于正常人，且ＭＡＰ与６－ｋｅｔｏ－ＰＧＦ１ａ呈负相关。提示晚血患者体内ＴＸＡ２－ＰＧＩ２平衡失调     

幽门螺杆菌感染者长期饮酒时PGE2与胃癌相关病变的关系

目的探讨长期饮酒合并幽门螺杆菌感染患者胃液及血液中PGE2与胃癌相关性病变的关系。方法 2007年1月-2010年12月符合条件的幽门螺杆菌感染同时长期饮酒56例和单纯长期饮酒64例患者,进行内镜下胃黏膜组织活检并进行病理学观察,同时抽静脉血及胃液用ELISA法检测PGE2浓度。结果幽门螺杆菌感染同时长期饮酒组中胃黏膜轻度萎缩亚组和轻度肠化亚组患者血清PGE2浓度明显高于长期饮酒胃黏膜轻度萎缩亚组和轻度肠化亚组患者血清PGE2浓度(P=0.02或P=0.01)。长期饮酒合并幽门螺杆菌阳性感染组中胃黏膜有不典型增生亚组患者血清PGE2浓度明显高于长期饮酒组中胃黏膜有不典型增生亚组患者(P=0.02)。两组患者各亚组之间胃液PGE2浓度对比,差异无统计学意义(P均>0.05)。结论幽门螺杆菌感染同时长期饮酒患者血液PGE2浓度升高与胃黏膜轻度萎缩和肠化及不典型增生之间存在明显关系,但胃液中PGE2与胃黏膜萎缩、肠化和不典型增生之间无明显关系。     

长期饮酒合并幽门螺杆菌感染时胃黏膜损伤程度与EGF和PGE2的关系

目的探讨长期饮酒合并幽门螺杆菌感染时胃黏膜损伤的程度与胃液及血液中EGF及PGE2之间的关系。方法对2007年1月～2010年12月符合条件的长期饮酒合并幽门螺杆菌感染的56例患者进行内镜下胃黏膜活检组织的病理学观察,同时抽静脉血及胃液用ELISA法检测EGF及PGE2浓度。结果长期饮酒合并幽门螺杆菌感染胃黏膜中重度慢性炎症组患者血清和胃液EGF浓度明显高于轻度慢性炎症组患者血清和胃液EGF浓度(P=0.000;P=0.018);胃黏膜中重度萎缩组患者血清EGF浓度明显高于胃黏膜轻度萎缩组患者血清EGF浓度(P=0.000);胃黏膜中重度肠化组患者血清EGF浓度明显高于胃黏膜胃黏膜轻度肠化组患者血清EGF浓度(P=0.000),而胃黏膜中重度肠化组患者血清PGE2浓度明显降低(P=0.034);胃黏膜有不典型增生组患者血清和胃液中EGF浓度明显高于胃黏膜无不典型增生组患者血清和胃液中EGF浓度(P=0.000;P=0.044)。结论长期饮酒合并幽门螺杆菌感染引起血液中EGF升高与患者胃黏膜慢性炎症、萎缩和肠化加重及不典型增生的发生有关。而胃液中EGF浓度的升高仅与胃黏膜慢性炎症和不典型增生发生相关。在胃黏膜肠化患者中血清中PGE2明显降低。     

环氧合酶-1和前列腺素E2在多潘立酮对大鼠胃黏膜保护中的作用

目的　研究多潘立酮对大鼠胃黏膜损伤是否具有保护作用 ,并探讨胃黏膜细胞中环氧合酶 1(COX 1)及前列腺素 (PG)E2是否参与其中。方法　研究分为对照组和实验组。后者分别用多潘立酮 0 .5mg/kg、1mg/kg和 2mg/kg灌胃 ,3次 /d ,连续 3d。各组大鼠灌入无水乙醇后 ,肉眼观察胃黏膜损伤指数 (LI) ,光镜下观察黏膜缺损深度 ,并计算黏膜缺损深度与胃壁全层厚度百分比。放射免疫法测定各组胃黏膜PGE2的水平。免疫组织化学方法检测COX 1和COX 2蛋白表达水平并以平均吸光度值表示其强度。RT PCR检测胃黏膜COX 1和COX 2mRNA表达变化。结果　多潘立酮 1mg/kg组的LI及黏膜缺损深度与胃壁全层厚度百分比显著低于对照组 (P <0 .0 5 ) ,0 .5mg/kg组和 2mg/kg的组LI亦显著低于对照组 (P <0 .0 5 )。多潘立酮 1mg/kg组大鼠胃黏膜COX 1蛋白表达水平及PGE2水平显著高于空白对照组 (P <0 .0 1)。各实验组和对照组在胃黏膜细胞内均无COX 2蛋白表达。三个实验组COX 1mRNA表达量与对照组比较差异均有显著性 (P <0 .0 1)。各组均未检测到COX 2mRNA表达。结论　多潘立酮对胃黏膜损伤具有保护作用 ,其机制之一可能与其增加胃黏膜COX 1mRNA和COX 1蛋白表达及促进胃黏膜PGE2分泌有关。     

Protective effect of colloidal bismuth subcitrate on gastric mucosal lesion induced by aspirin

This study was designed to investigate the protective effect of colloidal bismuth subcitrate (CBS) on aspirin-induced gastric mucosal lesion 20 patients with arthralgia were allocated into this study. All of them were free of gastrointestinal symptom and their gastric mucosa were nearly normal under gastroendoscopic observation. The first group of 10 patients received orally aspirin 1.5 qid for 4 days. The second group also of 10 patients was treated with CBS 120 mg qid and after 2 days they received aspirin and CBS simultaneously in the dosage mentioned above for another 4 days. Before and after treatment, the patients of both groups were examined endoscopically. After treatment, the mucosal inflammation was much less in the second group than that in the first group. The prostaglandin E2 concentration of antral mucosa in the first group was reduced significantly after administration of aspirin alone, while that in the second group was slightly increased after a combined treatment of aspirin and CBS. The results demonstrate that CBS is an effective agent in prevention of gastric lesion induced by aspirin and prostaglandin E may be involved in this mucosal protective effect.     

Distribution of prostaglandins in gastric and duodenal mucosa of healthy subjects and duodenal ulcer patients: effects of aspirin and paracetamol.

The distribution of mucosal PGE2-like activity was determined by bioassay technique in the body and antrum of the stomach and in the duodenum of healthy subjects and duodenal ulcer patients before and after administration of aspirin, paracetamol, or histamine. In healthy subjects, the oxyntic, antral and duodenal mucosa was found to be capable of generating large amounts of PGE2, which were not significantly different from those found in duodenal ulcer patients. No correlation was found between the generation of PGE2 and gastric acid secretory status or serum gastrin level. Aspirin-and to a much lesser extent, paracetamol-caused a dramatic reduction in the ability of the gastric mucosa to biosynthesis PGE2 and this was accompanied by marked side-effects and injury to the gastric mucosa. Administration of histamine caused small but significant reduction in the biosynthesis of PGE2 but it was accompanied by marked mucosal damage. This study indicates that the gastric and duodenal mucosa is capable of generating PGE2-like activity which may be involved in the mechanism that protects the mucosa against the damage caused by aspirin.     

Gastrocytoprotection by colloidal bismuth subcitrate (De-Nol) and sucralfate. Role of endogenous prostaglandins.

This study compares the gastroprotective effects of colloidal bismuth subcitrate (De-Nol) with those of sucralfate and a methylated analogue of prostaglandin E2 (PGE2) against acute gastric lesions induced by acidified aspirin and absolute ethanol in rats. Both De-Nol and sucralfate given orally prevented dose dependently the formation of gastric lesions by these ulcerogens, De-Nol being, respectively, twice and seven times more potent, on a weight basis, than sucralfate. As the gastroprotective activities of both De-Nol and sucralfate on ethanol lesions can be reversed by pretreatment with indomethacin and as De-Nol and sucralfate increase the mucosal generation and luminal release of PGE2, we postulate that mucosal prostaglandins may be involved in the mechanism of action of these drugs on the gastric mucosa.     

Potentiation of aspirin-induced gastric lesions by exposure to cold in rats. Role of acid secretion, mucosal blood flow, and gastric mucosal prostanoid content

We investigated the mechanism by which exposure to cold sensitizes rats to the formation of gastric lesions after a low dose of aspirin (50 mg/kg). Six times more lesions were produced by aspirin plus cold than by aspirin alone. Three hypotheses were studied to explain the synergism of aspirin plus cold on lesion formation: gastric acid hypersecretion, reduced gastric mucosal blood flow, and decreased prostanoid synthesis by the stomach. Cold, and cold plus aspirin, stimulated gastric acid secretion (to a similar extent), whereas aspirin had no effect. Gastric mucosal blood flow, measured by the hydrogen gas clearance method, was decreased by cold, aspirin, and aspirin plus cold, and the extent of decrease was similar. Prostanoid generation [prostaglandin E2 (PGE2), PGF2 alpha, 6-keto PGF1 alpha, and thromboxane B2] by the gastric corpus mucosa was not affected by cold, but was reduced equally (by at least 90%) in animals receiving aspirin alone or aspirin plus cold. After oral administration of aspirin, the plasma contained mostly salicylic acid (98%), whereas the gastric mucosa contained mostly aspirin (80%-85%). We conclude that the synergism of aspirin plus cold on the formation of gastric lesions probably results from the combined effects of three factors: increased secretion of acid (because of exposure to cold) that is in contact with a gastric mucosa in which blood flow is reduced (because of exposure to cold or to aspirin), and in which the synthesis of cytoprotective prostaglandins is inhibited (by aspirin). Such mucosa may be particularly vulnerable to the damaging effect of hyperacidity.     

大鼠胃黏膜SS、EGF、PGE_2含量在模拟+Gz值暴露下的变化及机制

目的观察模拟不同+Gz值暴露对大鼠应激性胃黏膜损伤程度;探讨胃黏膜保护因子胃黏膜中生长抑素(SS)、表皮生长因子(EGF)、前列腺素E2(PGE2)含量及其可能抗损伤机制。方法 40只雄性Wistar大鼠随机分成4组,+Gz暴露方式采用动物离心机模拟+Gz暴露,每组10只同时上机。采用梯形+Gz作用曲线,G值增长率1 G/s,由计算机进行加速度程序控制:A组(对照组):+1 Gz值暴露(n=10),连续暴露5 min;B组:+5 Gz值暴露(n=10),连续暴露5 min;C组:+10 Gz值暴露(n=10),连续暴露5 min;D组:重复暴露组(n=10),+5 Gz值1.5 min,+10 Gz值2 min,+5 Gz值1.5 min。每组下离心机后,光镜下分别观察各组胃黏膜大体损伤程度;制成切片,进行HE染色观察胃黏膜组织病理学改变。放免法检测胃黏膜EGF、SS、PGE2的含量。结果光镜和HE染色观察胃黏膜组织病理学改变显示:胃黏膜损伤程度由轻到重依次为A、B、C、D组,C、D组与A组比较病理损害明显加重。与A组比较,B、C、D组胃黏膜EGF、PGE2的含量显著减少(P0.05);大鼠胃黏膜中SS含量(ng/mg)明显升高(1.258±0.050、4.775±0.289、6.581±0.479、8.114±0.662)(P0.05);EGF含量(ng/mg)下降(0.677±0.066、0.472±0.055、0.383±0.031、0.256±0.019)(P0.05);PGE2水平(ng/mg)减少(6.106±0.640、5.116±0.660、4.510±0.699、3.473±0.337)(P0.05)。结论越高水平+Gz值暴露对大鼠胃黏膜损伤程度越大;作为保护因子的胃黏膜SS水平反应性增高,同时EGF、PGE2的含量减少。SS、EGF和PGE2在不同+Gz值暴露胃黏膜应激过程中起到重要抗损伤的保护作用。     

急性冠脉综合征患者介入治疗早期增加阿司匹林和氯吡格雷剂量对主要不良心血管事件的影响

目的:观察急性冠脉综合征（ACS）患者经皮冠状动脉介入治疗（PCI）早期不同剂量阿司匹林、氯吡格雷对主要不良心血管事件（MACE）的影响。方法: 选择2007年12月～2009年12月ACS行PCI术的患者102例,所有患者按入院先后随机分为两组,1组为加量组（n=54）,患者入院后阿司匹林300 mg顿服,然后300 mg,每日1次,口服1个月后改为100 mg,每日1次,长期口服;氯吡格雷150 mg ,每日1次,1周后改为75 mg,每日1次,口服1年。另1组为对照组（n=48）,患者入院后阿司匹林100 mg,每日1次,以后长期按此剂量口服。氯吡格雷75 mg,每日1次,口服1年。两组患者其他治疗低分子肝素等方法相同。分别于PCI术后1个月、6个月时比较MACE的发生情况。结果: 两组患者临床基线特征基本一致,病变血管分布情况差异无统计学意义。其MACE发生情况在第一个月时,加量组低于对照组,但差异未到达显著水平（7% vs.15%）;在第6个月时,加量组低于对照组,差异具有统计学意义（2% vs. 17%,P<0.05）。结论: ACS患者在一般治疗的基础上,介入治疗时早期增加阿司匹林、氯吡格雷的剂量可降低PCI术后MACE的发生率。