糖尿病合并微血管病变患者血小板聚集、血栓烷B_2生成与cAMP含量关系的初步探讨

本文对40例糖尿病患者的血小板聚集、血栓烷B_2生成和cAMP含量进行测定并探讨其与微血管病变的关系。结果表明:糖尿病患者血小板聚集增强、血栓烷B_2生成增加,血小板cAMP含量降低。上述改变在无合并微血管病变组已存在,参与微血管病变的发生和发展。血小板血栓烷B_2生成增加可能与血小板膜磷脂酶活性有关。     

Low phospholipid arachidonic acid values in diabetic platelets

Platelet aggregation is enhanced in diabetes mellitus, and platelets may be implicated in the pathogenesis of diabetic angiopathy. Increased platelet aggregation is probably mediated by the production of the proaggregatory prostaglandin thromboxane, which is synthesised from arachidonic acid (C20:4) by the action of the platelet enzymes cyclo-oxygenase and thromboxane synthetase. The fatty acid composition of platelet phospholipid was measured in 20 normal controls, 10 insulin-treated diabetics with no or minimal retinopathy, and 10 insulin-treated diabetics with proliferative retinopathy. The percentage of arachidonic acid was significantly higher in controls (mean 22.6%) than in the diabetics with no or minimal retinopathy (mean 18.5%; p less than 0.025) and the diabetics with proliferative retinopathy (mean 14.6%; p less than 0.001). The percentage of linoleic acid was lower in controls (mean 8.9%) than in the diabetics with no or minimal retinopathy (mean 12.6%; p less than 0.01) and diabetics with proliferative retinopathy (mean 13.1%; p less than 0.001). The mean percentage of linolenic acid was significantly lower in the diabetics with proliferative retinopathy (2.7%) than in the normal control group (4.4%; p less than 0.01). A significant negative correlation was found between the percentages of arachidonic acid and glycosylated haemoglobin (Rs = -0.58; p less than 0.001). A significant positive correlation was found between linoleic acid and the percentage of glycosylated haemoglobin (Rs = 0.51; p less than 0.01). The reciprocal correlation between percentages of arachidonic acid and glycosylated haemoglobin suggests that diabetic control may influence thromboxane release and platelet activity directly and that low percentages of arachidonic acid reflect the increased degree of in-vivo activation.     

Antithrombotic effects of Andrographis paniculata nees in preventing myocardial infarction.

In 16 dogs the endothelium of the left anterior descending coronary artery was injured mechanically. Then a copper wire was inserted into the lumen as a choke of flow and the vessel was slightly compressed from outside by a constrictor. Eight dogs had been treated beforehand with a preparation of flavone extracted from the root of the Chinese medicinal herb Andrographis paniculata (TFAP). In the control group, saline solution was given, the epicardially recorded ST segment started to elevate within 15 minutes, the platelet aggregation rate and the plasma levels of TXB2 increased rapidly, whereas the level of 6-k-PGF1 alpha remained stable. Platelet cGMP rose continuously; however, platelet cAMP rose only at 60 minutes. Histological findings confirmed the occurrence of arterial thrombus and myocardial necrosis. Contrariwise, in the pretreated group there was no elevation of the ST segment, plasma 6-k-PGF1 alpha and platelet cAMP were increased, the production of TXB2 and aggregation of platelets were inhibited, and no thrombus or myocardial infarction was induced. All data suggest that TFAP might promote the synthesis of PGI2, inhibit the production of TXA2, stimulate the synthesis of cAMP in platelets, impede aggregation of platelets, and thereby prevent the formation of thrombi as well as the development of myocardial infarction.

     

Effects of Codonopsis pilosulae on the synthesis of thromboxane A2 and prostacyclin

24 angina pectoris patients were treated with Codonopsis pilosulae (CP) oral solution 20 ml (containing crude CP 20 g) thrice daily for 7 days, other 10 cases were treated by aspirin 0.5 g per day for a week as the control group. After treatment, in the CP group, the plasma level of TXB2 was obviously reduced from 156.76 +/- 11.87 pg/ml to 125.01 +/- 8.85 pg/ml (means +/- S means), the inhibitory rates was 15. 67% (P less than 0.05), and of 6-keto-PGF1 alpha (6-K) was not markedly changed (P greater than 0.05). In the aspirin group, TXB2 was also reduced significantly (P less than 0.05); 6-K was reduced more than that of CP group, the inhibitory rate was 24.33 +/- 9.40% (P less than 0.05). To reveal the mechanism of CP action on the synthesis of TXA2 and PGI2, the porcine lung microsome was used as the donor of cyclooxygenase, thromboxane synthase and prostacyclin synthase, the effects of CP on the formation of TXB2 and 6-K from arachidonic acid (AA) or endoperoxides were measured by RIA respectively. The results showed that both the levels of the formation of TXB2 from AA or endoperoxides were markedly reduced by CP in a dose-dependent (at doses of 3-300 mg/ml). The synthesis of TXB2 was distinctly inhibited alone with a dose of 100 mg/ml CP, which suggested that CP might be an inhibitor of TXB2 synthase at that dose; while at a dose of 300 mg/ml CP, the synthesis of TXB2 and 6-K were inhibited simultaneously (P less than 0.001). It showed that a larger dosage of CP, which could inhibited the synthesis of both TXA2 and PGI2, its mechanism of action needs further study.     

Inhibitory effect of panicoin on platelet activation and its mechanism

Inhibitory Effect of Panicoin on Platelet Activation and Its Mechanism@韩谷鸣$Xuzhou Geriatrics Institute!Jiangsu 221003 @姚倩$Xuzhou Geriatrics Institute!Jiangsu 221003 @李洪莲$Xuzhou Geriatrics Institute!Jiangsu 221003     

Effects of Ligusticum wallichii on the plasma levels of beta-thromboglobulin, platelet factor 4, thromboxane B2 and 6-keto-PGF1 alpha in rabbits under acute experimental cerebral ischemia

By occluding the bilateral carotid arteries of rabbits to produce bilateral partial cerebral ischemia, and by using RIA and ELISA to measure the levels of Beta-thromboglobulin (beta-TG), platelet factor 4 (PF4), thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) in plasma, the authors found that the levels of beta-TG, PF4 and TXB2 in plasma had significantly increased (P less than 0.01), but the level of 6-keto-PGF1 alpha in plasma showed no change (P greater than 0.05) after cerebral ischemia appeared. The results of the Ligusticum wallichii (Ligusticum) pre-treatment to the test-group showed that the levels of beta-TG, PF4 and TXB2 in plasma had significantly decreased (P less than 0.01), and the level of 6-keto-PGF1 alpha in plasma had significantly increased (P less than 0.05). This suggested that the Ligusticum treatment could effectively inhibit the platelet activation in vivo and correct the TXA2-PGI2 imbalance in blood after cerebral ischemia. In this study, some new approaches were explored to explain the mechanisms of Ligusticum for preventing and treating cerebral ischemia.     

当归注射液对冠心病患者血超氧化物歧化酶活性和脂质过氧化物的影响

２４例冠心病患者静脉滴注当归注射液治疗后，血超氧化物歧化酶（ＳＯＤ）、６－酮前列腺素Ｆ１α（６－Ｋ）和６－Ｋ／血栓素Ｂ２（ＴＸＢ２）均升高，丙二醛（ＭＤＡ）、ＴＸＢ２和血小板最大聚集率均降低（Ｐ均＜０．０５～０．０１）。结果表明，当归注射液有增加ＳＯＤ活性，清除氧自由基，抗脂质过氧化反应，减低ＭＤＡ水平，升高ＰＧＩ２，降低ＴＸＡ２，调整ＰＧＩ２／ＴＸＡ２平衡和抑制血小板聚集的作用。     

FI,FIS等载体衍生物对兔血小板聚集和TXB2释放的影响

目的 通过测定兔血小板聚集和ＴＸＢ２的含量,比较观察Ｆ、Ｉ、ＦＩ、ＦＩＳ在抗血栓方面的药理作用特点。方法 用比浊法＾（４）和放免法＾（７）测定Ｆ、Ｉ、ＦＩ、ＦＩＳ在体外对兔血小板聚集及释放的ＴＸＢ２的影响。结果 连有阿魏到和吲哚美辛的载体衍生物ＦＩ,ＦＩＳ可抑制ＡＡ、ＡＤＰ诱导的血小板聚集,在１０￣２５０μｍｏｌ·Ｌ＾－１的剂量范围内,两药的作用呈剂量依赖关系,ＦＩ、ＦＩＳ２４０μｍｏｌ·＾－１对     

冠心病患者治疗前后血小板膜糖蛋白GPⅡb/Ⅲa、血栓素B2的变化

目的：观察冠心病（CHD）患者治疗前后血小板膜糖蛋白（GPⅡb/Ⅲa）表达和血浆血栓素B2（TXB2）水平的变化,探讨其临床意义。方法：分别采用流式细胞术（FCM）、酶联免疫吸附法（ELISA）检测60例CHD患者（CHD组）接受阿司匹林（100mg/d）治疗前、治疗2周后及20名健康体检者（正常对照组）的血小板膜糖蛋白GPⅡb/Ⅲa表达阳性率、血浆TXB2水平。结果：治疗后,CHD患者血小板膜糖蛋白GPⅡb/Ⅲa表达阳性率、血浆TXB2水平均比治疗前明显降低（P〈0.01）,但仍高于正常对照组（P〈0.01）。结论：阿司匹林可在一定程度上抑制CHD患者血小板活化与聚集。     

糖尿病患者血小板游离钙变化与血栓素B2生成的关系

为了探讨糖尿病患者血小板胞浆内游离Ｃａ￣（２＋）浓度（［Ｃａ￣（２＋）］ｉ）与血栓素Ｂ＿２（ＴＸＢ＿２）生成的关系，及其在糖尿病微血管病变发病中的作用，作者用Ｃａ￣（２＋）荧光指示剂ｆｕｒａ－２直接测定２７例糖尿病患者（合并微血管病变苔１３例，无微血管病变者１４例）血小板［Ｃａ￣（２＋）］ｉ，并且同步测定ＴＸＢ＿２。结果：以钙载体Ａ＿（２３１８７）诱导，糖尿病组血小板［（Ｃａ￣（２＋）］ｉ峰值为１１４７±５２ｎｍｏｌ／Ｌ，高于对照组（８９７±４９ｎｍｏｌ／ＬＰ＜０．０１），且与ＴＸＢ，生成呈正相关：而用花生四烯酸诱导，糖尿病组血小板［Ｃａ￣（２＋）］ｉ峰值为３５３±１４ｎｍｏｌ／Ｌ，虽高于对照组（３１２±１６ｎｍｏｌ／Ｌ，Ｐ＜０．０５），但与ＴＸＢ＿２生成未呈显著相关。上述改变在糖尿病有或无微血管病变两组之间比较无显著性差异，提示糖尿病患者血小板［Ｃａ￣（２＋）］ｉ变化可能通过膜磷脂酶环节致使ＴＸＢ＿２生成增多，参与微血管病变的发病。     

茶黄烷醇类对血小板功能影响的进一步研究

本文进一步研究了茶黄烷醇类(TF)对血小板聚集以及人血小板丰富血浆产生TXA_2的影响.实验结果表明,TF不但显著地抑制ADP、肾上腺素(Adr),花生四烯酸(AA)诱导的血小板聚集,还明显地抑制了血小板聚集曲线的幅度.高浓度TF对ADP诱导的血小板聚集的抑制程度大于低浓度TF;与阿斯匹林相似,TF不能对已发生聚集的血小板起解聚作用;TF还能明显地抑制人血小板丰富血浆产生血栓素B_2(TXB_2).12名陈旧性心肌梗塞患者经服用粗制的TF2个月后,血小板聚集性及TXB_2水平显著下降.     

高血压对糖尿病微血管病变患者血浆TXB2浓度的影响

用放射免疫法测定２０４例糖尿病人的血浆ＴＸＢ２和６－Ｋｅｔｏ－ＰＧＦ１ａ浓度。各组的ＴＸＢ２水平，随糖尿病视网膜病变或糖尿病肾病加重而升高。各糖尿病微血管病变组中高血压组ＴＸＢ２水平均高于血压正常组（Ｐ＜０．０５）。提示ＴＸＢ２在糖尿病微血栓形成中起重要作用，合并高血压时对糖尿病微血管病变的发生和进展有明显的促进作用。     

老年糖尿病肠病患者血小板功能、血栓素B_2及6－酮－前列腺素F_（1α）的变化

对１８例老年糖尿病肠病患者和２２例糖尿病无肠病者的血小板聚集、血栓素Ｂ２（ＴＸＢ２）和６－酮－前列腺素Ｆ１α（６－ｋｅｔｏ－ＰＧＦ１α）进行测定，并且与健康老年人比较。结果表明：肠病组血小板聚集率和肠病组、无肠病组血浆ＴＸＢ２、ＴＸＢ２／６－ｋｅｔｏ－ＰＧＦ１α比值均明显高于健康人组（Ｐ＜０．０１），而６－ｋｅｔｏ－ＰＧＦ１α则明显降低（Ｐ＜０．０１）。肠病组血小板聚集率、ＴＸＢ２及ＴＸＢ２／６－ｋｅｔｏ－ＰＧＦ１α比值变化较无肠病组更为明显（Ｐ＜０．０１）。这提示血小板功能亢进和血栓素Ａ２（ＴＸＡ２）与前列环素（ＰＧＩ２）间平衡失调可能在老年糖尿病肠病的发病过程中起着一定作用。     

Prostacyclin and thromboxane in diabetes

Concentrations of the stable antiaggregatory prostacyclin metabolite 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and of the proaggregatory thromboxane A2 metabolite thromboxane B2 were measured by radioimmunoassay in plasma from 53 diabetics. In 33 of these patients the ability of platelets to produce thromboxane B2 during spontaneous clotting was also studied. Plasma 6-keto-PGF1 alpha concentrations were higher (p less than 0.05) in the diabetics (mean 107.7 +/- SE 7.6 ng/l) than in non-diabetic controls matched for age and sex (87.5 +/- 4.7 ng/l), and diabetics with microangiography (n = 28) and higher (p less than 0.01) concentrations (124.3 +/- 10.8 ng/l) than those without microangiography (n = 25; 89.2 +/- 9.3 ng/l). Plasma thromboxane B2 concentrations were also higher (p less than 0.01) in the diabetics (mean 218.5 +/- SE 25.3 ng/l) than in the controls (127.7 +/- 9.8 ng/l), but this increase was not related to microangiography. The ability of platelets to generate thromboxane B2 did not differ between the diabetics (181.4 +/- 16.4 microgram/l) and controls (195.8 +/- 11.8 microgram/l). Platelets of diabetics with microangiopathy or taking oral hypoglycaemic agents (n = 19), however, produced decreased amounts of thromboxane B2 during clotting. Plasma concentrations of 6-keto-PGF1 alpha and thromboxane B2 were not related to concentrations of glucose, haemoglobin A1, high-density lipoprotein cholesterol, cholesterol, triglycerides, magnesium, or creatinine. These results suggest that in diabetics with microangiopathy a balance between prostacyclin and thromboxane A2 is shifted to dominance by prostacyclin.     

毛葡萄叶水提物抑制血小板聚集的初步研究

目的探讨毛葡萄叶水提物（Gx）对血小板聚集的影响。方法分离健康人的血小板,与不同生药浓度的Gx于37℃孵育10 min后,检测胶原（collagen）和凝血酶（thrombin）诱导的人血小板聚集的变化。小鼠腹腔注射Gx后,分离小鼠血小板,检测二磷酸腺苷（ADP）诱导的血小板聚集的变化。结果 Gx对2μg/ml collagen诱导的血小板聚集有显著抑制作用（P〈0.05）,且呈现Gx的剂量依赖性（P〈0.05）;只有0.01 mg/ml的Gx对0.1 U/mlthrombin诱导的血小板聚集有抑制作用,且不呈现Gx的剂量依赖性。同时,Gx可抑制ADP诱导的腹腔注射Gx的小鼠血小板聚集,且呈现ADP剂量依赖性。结论 Gx具有明显抗血小板聚集作用,为开发抗血栓药物提供了实验依据。     

纤维蛋白原和红细胞比积在2型糖尿病微血管病变中的临床意义分析

目的探讨血浆纤维蛋白原和红细胞比积在糖尿病微血管病变的发生和发展过程中的作用。方法按统一要求测定124例糖尿病患者及30例正常人的血浆纤维蛋白原和红细胞比积。结果糖尿病患者血浆纤维蛋白原和红细胞比积均明显升高（P〈0．01）。在伴有微血管病变中变化更明显（P〈0．01）。结论两者共同参与了糖尿病微血管病变的发生和发展。     

大叶紫珠对大鼠凝血功能及TXB2、6-keto-PGF1a表达的影响

目的:观察大叶紫珠对大鼠凝血功能及血浆血栓素B2(thromboxane B2,TXB2)和6-酮-前列腺素F1a(6-keto prostaglandin F1a,6-keto-PGF1a)水平的影响。方法:40只健康Wistar大鼠随机分为正常组(生理盐水)、云南白药组(0.9g·kg-1)、紫珠叶提取物高剂量组[10 g(生药)·kg-1]和紫珠叶提取物低剂量组[5 g(生药)·kg-1],连续给药7 d。观察大叶紫珠小鼠灌胃给药对凝血酶原时间(prothrombin time,PT)、活化部分凝血活酶活性时间(activated partial thromboplastin time,APTT)、凝血酶时间(thrombin time,TT)、纤维蛋白原含量(content of fibrinogen,FIB)、TXB2和6-keto-PGF1a水平的影响。结果:与正常组比较,大叶紫珠水煎液高剂量组、低剂量组能明显缩短大鼠的PT、TT、APTT,显著增加FIB、TXB2的水平,同时能降低6-keto-PGF1a水平,且差异均有统计学意义(P0.05)。结论:大叶紫珠水煎液可能通过激活内源性、外源性凝血系统和调节TXB2、6-keto-PGF1a水平发挥止血作用。     

非胰岛素依赖型糖尿病人血浆血栓素B_2与6-酮-前列腺素F_(1α)水平改变及临床意义初步探讨

本文报告118例非胰岛素依赖型糖尿病(NIDDM)病人及81例正常对照者血浆血栓素B_2(TXB_2)与6—酮—前列腺素F_(1α)(6—酮—PGF_(1α))及血脂等测定结果,发现糖尿病人TXB_2水平增高,6—酮—PGF_(1α)水平降低,在合并冠心病组尤明显;血脂、血压、体重指数(BMI)、不同的治疗方式对TXB_2与6—酮—PGF_(1α)的改变有一定影响。结果提示血栓素A_2(TXA_2)与前列环素(PGI_2)之间的平衡失调在冠心病发病学上可能起一定作用,临床上纠正其失调以及脂代谢紊乱可能对防治糖尿病大血管病变有一定裨益。     

动脉粥样硬化高危人群中阿司匹林抵抗调查分析

目的调查社区动脉粥样硬化高危人群中阿司匹林抵抗(AR)或半抵抗(ASR)的发生率及其流行病学特征,并探讨其与危险因素的相关性。方法筛选200例动脉粥样硬化高危患者服用阿司匹林(100mg/d)至少7天以上,用二磷酸腺苷(ADP)和花生四烯酸(AA)作诱导剂测定其前后血小板聚集功能变化及血清血栓烷B2(TXB2)水平测定。结果200例动脉粥样硬化高危人群中AR发生率为4.5%,ASR者占20.7%。血清TXB2,AA、ADP诱导的血小板聚集率与健康对照组相比有显著统计学差异(P<0.01);血清TXB2与血小板聚集率有较好的相关性(r=0.871)。结论社区动脉粥样硬化高危人群服用阿司匹林后部分产生AR或ASR;AR或ASR人群发生冠心病事件的风险高于阿司匹林敏感(AS)人群;检测AA、ADP诱导的血小板聚集率,血清TXB2可作为动脉粥样硬化高危人群发生AR或ASR的评价指标。     

EFFECT OF 764－3 ON AGGREGATION AND CALCIUM MOVEMENTS IN AEQUORIN－LOADED HUMAN PLATELETS

ＥＦＦＥＣＴＯＦ７６４－３ＯＮＡＧＧＲＥＧＡＴＩＯＮＡＮＤＣＡＬＣＩＵＭＭＯＶＥＭＥＮＴＳＩＮＡＥＱＵＯＲＩＮ－ＬＯＡＤＥＤＨＵＭＡＮＰＬＡＴＥＬＥＴＳＷｕＨｕａｉｚｈｕ武怀珠；ＬｉＪｉａｚｅｎｇ李家增；ＰｅｎｇＬｉｎ彭林；ＴｅｎｇＢｉｎ滕彬ａｎｄＺ...