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竹叶青蛇(白唇竹叶青和大眼竹叶青)毒液对人体纤溶系统的影响。

The effects of green pit viper (Trimeresurus albolabris and Trimeresurus macrops) venom on the fibrinolytic system in human.

作者信息

Rojnuckarin P, Intragumtornchai T, Sattapiboon R, Muanpasitporn C, Pakmanee N, Khow O, Swasdikul D

机构信息

Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

出版信息

Toxicon. 1999 May;37(5):743-55. doi: 10.1016/s0041-0101(98)00214-1.

Abstract

Green pit viper (Trimeresurus albolabris and Trimeresurus macrops) venom was found to have a thrombin-like effect in vitro but cause a defibrination syndrome in vivo. The effects of venom on fibrinolytic system have not been well characterized. This knowledge can help to define the roles of antifibrinolytic therapy, give insights in fibrinolytic system regulation and potentially lead to identification of a new profibrinolytic agent from this venom. Forty-six cases of green pit viper bites were studied for various coagulation and fibrinolytic parameters and correlated with serum venom levels measured by ELISA. Fibrinolytic system activation is very common as indicated by low plasminogen (50%), low antiplasmin (56.5%) and elevated fibrin-fibrinogen degradation products (FDPs, 97.4%) levels. FDP test is very sensitive and a normal level is useful for exclusion of systemic envenomation. In contrast to some other models of defibrination syndrome, such as Russell viper (Daboia russelli siamensis), elevation of plasminogen activator activity (PA) was found indicating a hyperfibrinolytic state. Definite increase in tissue-type plasminogen activator (t-PA) antigen (p = 0.00075) with a modest elevation of its inhibitor plasminogen activator inhibitor-1 (PAI-1) (p = 0.27) probably contributes to this effect. This supports the idea that the balance between plasminogen activators and inhibitors can determine fibrinolytic responses in pathologic states. Fibrinopeptide A levels were markedly elevated (68.43 +/- 51.57 ng/ml in cases and 2.83 +/- 3.80 ng/ml in control, p < 0.0001) and correlated well with clinical severity suggesting that the fibrin deposition from the thrombin-like effect is the main mechanism of fibrinolysis. Therefore, antifibrinolytic agents probably have no role in treatment. However, the components of green pit viper venom that have these profibrinolytic effects in human are interesting and should be further identified.

摘要

竹叶青蛇(白唇竹叶青蛇和大眼竹叶青蛇)毒液在体外被发现具有类凝血酶作用,但在体内会引发去纤维蛋白综合征。毒液对纤溶系统的影响尚未得到充分表征。这些知识有助于明确抗纤溶治疗的作用,深入了解纤溶系统的调节,并有可能从这种毒液中鉴定出一种新的促纤溶药物。对46例竹叶青蛇咬伤病例进行了各种凝血和纤溶参数的研究,并与通过酶联免疫吸附测定法(ELISA)测得的血清毒液水平进行了相关性分析。纤溶系统激活非常常见,表现为纤溶酶原水平低(50%)、抗纤溶酶水平低(56.5%)以及纤维蛋白-纤维蛋白原降解产物(FDPs)水平升高(97.4%)。FDP检测非常敏感,正常水平有助于排除全身中毒。与其他一些去纤维蛋白综合征模型(如泰国圆斑蝰蛇)不同,发现纤溶酶原激活物活性(PA)升高,表明处于高纤溶状态。组织型纤溶酶原激活物(t-PA)抗原明显增加(p = 0.00075),其抑制剂纤溶酶原激活物抑制剂-1(PAI-1)略有升高(p = 0.27),这可能是造成这种效应的原因。这支持了纤溶酶原激活物和抑制剂之间的平衡可以决定病理状态下纤溶反应的观点。纤维肽A水平显著升高(病例组为68.43±51.57 ng/ml,对照组为2.83±3.80 ng/ml,p < 0.0001),且与临床严重程度密切相关,表明类凝血酶作用导致的纤维蛋白沉积是纤溶的主要机制。因此,抗纤溶药物可能在治疗中不起作用。然而,竹叶青蛇毒液中在人体内具有这些促纤溶作用的成分很有意思,应该进一步加以鉴定。

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