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抗血小板血清对兔损伤诱导的血栓动脉粥样硬化病变的抑制作用。

Inhibition of injury induced thromboatherosclerotic lesions by anti-platelet serum in rabbits.

作者信息

Moore S, Friedman R J, Singal D P, Gauldie J, Blajchman M A, Roberts R S

出版信息

Thromb Haemost. 1976 Feb 29;35(1):70-81.

PMID:989195
Abstract

We have previously shown that repeated or continuous intimal injury caused by an indwelling aortic catheter causes a variety of lesions in rabbits maintained on a diet unsupplemented by lipid. These include fatty streaks, lipid-free fibrous plaques and lipid-rich raised thromboatherosclerotic plaques. Whether lipid-rich raised lesions are a result of injury or co-existing thrombosis or both is not clear. The present experiment was designed to answer this question. Anti-platelet serum (APS) to washed sonicated rabbit platelets was raised in sheep. PE 60 polyethylene catheters were placed in the aortas of 35 rabbits by way of a femoral artery. The animals were randomly divided into 2 groups. The experimental group (17 rabbits) received an intravascular injection of 1.0 ml of APS followed 8 hours later by a subcutaneous injection of 0.5 ml. Thereafter, 0.5 ml APS was given subcutaneously each day for 13 additional days. The control group (18 rabbits) received no APS. Platelet counts were done prior to surgery, at 5 minutes following surgery, at 4 days, 8 days and just prior to killing. Extent of lesions was estimated by photographing the opened aortas, projecting the photographs on cardboard, cutting out the areas occupied by the different lesions and weighing the cardboard. The mean weight of raised lesions in the control group was 6 to 7 times greater than in the experimental groups. Statistical analysis of this difference based on Welsh's "t" test for unequal variances was highly significant (P less than 0.001). Platelet counts in the experimental groups varied from 0 to 20,000 at 14 days. In animals with platelet counts less than or equal to 1,000 mm3 raised lesions were completely prevented. In a second experiment the effect of APS was compared with normal sheep serum (NSS). A similarly significant inhibition of raised lesions occurred in the APS group. The extent of lesions in the NSS control was similar to that in the No-APS group of the first experiment. These findings indicate that thrombosis is more important than injury in the development of lipid-rich raised lesions.

摘要

我们之前已经表明,留置主动脉导管引起的反复或持续性内膜损伤会在未补充脂质饮食的兔子身上引发多种病变。这些病变包括脂肪条纹、无脂质纤维斑块和富含脂质的隆起血栓性动脉粥样硬化斑块。富含脂质的隆起病变是损伤的结果还是同时存在的血栓形成的结果,或者两者皆是,尚不清楚。本实验旨在回答这个问题。用绵羊制备了针对洗涤并超声处理过的兔血小板的抗血小板血清(APS)。通过股动脉将PE 60聚乙烯导管置入35只兔子的主动脉。这些动物被随机分为两组。实验组(17只兔子)血管内注射1.0 ml APS,8小时后皮下注射0.5 ml。此后,在接下来的13天里每天皮下注射0.5 ml APS。对照组(18只兔子)未注射APS。在手术前、手术后5分钟、4天、8天以及处死前进行血小板计数。通过拍摄打开的主动脉、将照片投射到硬纸板上、剪出不同病变所占区域并称重硬纸板来估计病变程度。对照组中隆起病变的平均重量比实验组大6至7倍。基于Welsh氏不等方差“t”检验对该差异进行的统计分析具有高度显著性(P小于0.001)。实验组在14天时血小板计数在0至20,000之间。血小板计数小于或等于1,000 mm3的动物中,隆起病变完全得到预防。在第二个实验中,将APS的作用与正常绵羊血清(NSS)进行了比较。APS组中隆起病变同样受到显著抑制。NSS对照组的病变程度与第一个实验的未注射APS组相似。这些发现表明,在富含脂质的隆起病变形成过程中,血栓形成比损伤更重要。

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引用本文的文献

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Ann Transl Med. 2019 Sep;7(18):477. doi: 10.21037/atm.2019.08.06.
2
Safety and antithrombotic efficacy of moderate platelet count reduction by thrombopoietin inhibition in primates.通过抑制血小板生成素减少灵长类动物血小板计数的安全性和抗血栓疗效。
Sci Transl Med. 2010 Jun 23;2(37):37ra45. doi: 10.1126/scitranslmed.3000697.
3
Platelet activation releases megakaryocyte-synthesized apolipoprotein J, a highly abundant protein in atheromatous lesions.
血小板活化会释放巨核细胞合成的载脂蛋白J,这是一种在动脉粥样硬化病变中含量很高的蛋白质。
Am J Pathol. 1993 Sep;143(3):763-73.
4
The proliferation of neointimal smooth muscle cells cultured from rabbit aortic explants 15 weeks after de-endothelialization by a balloon catheter.通过球囊导管去内皮后15周,从兔主动脉外植体培养的新生内膜平滑肌细胞的增殖。
Int J Exp Pathol. 1994 Jun;75(3):169-77.
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The effect of acetylsalicylic acid (ASA) on the development of atherosclerotic lesions in miniature swine.乙酰水杨酸(ASA)对小型猪动脉粥样硬化病变发展的影响。
Br J Exp Pathol. 1980 Aug;61(4):440-3.
6
The Gordon Wilson Lecture: atherosclerosis--a response to injury gone awry.戈登·威尔逊讲座:动脉粥样硬化——对损伤的异常反应。
Trans Am Clin Climatol Assoc. 1982;93:78-86.
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Cultured endothelial cells produce a heparinlike inhibitor of smooth muscle cell growth.培养的内皮细胞产生一种平滑肌细胞生长的类肝素抑制剂。
J Cell Biol. 1981 Aug;90(2):372-9. doi: 10.1083/jcb.90.2.372.
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Atherosclerosis and a coronary artery bypass operation in a woman with von Willebrand disease.一名患有血管性血友病的女性的动脉粥样硬化与冠状动脉搭桥手术
West J Med. 1980 Dec;133(6):515-7.
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Long-term vasectomy: effects on the occurrence and extent of atherosclerosis in rhesus monkeys.长期输精管切除术:对恒河猴动脉粥样硬化发生情况及程度的影响。
J Clin Invest. 1980 Jan;65(1):15-25. doi: 10.1172/JCI109645.
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New mechanism for foam cell generation in atherosclerotic lesions.动脉粥样硬化病变中泡沫细胞生成的新机制。
J Clin Invest. 1987 Aug;80(2):367-73. doi: 10.1172/JCI113081.