Characterization of the Rabbit as an In Vitro and In Vivo Model to Assess the Effects of Fibrinogenolytic Activity of Snake Venom on Coagulation.
Characterization of the Rabbit as an In Vitro and In Vivo Model to Assess the Effects of Fibrinogenolytic Activity of Snake Venom on Coagulation.
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DOI：
10.1111/bcpt.12848
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发表时间：
2018-01
影响因子：
3.1
通讯作者：
Redford DT
中科院分区：
文献类型：
--
作者：
Nielsen VG;Sánchez EE;Redford DT
几项体外研究表明，通过用铁（Fe）和一氧化碳（CO）修饰纤维蛋白原来阻止催化作用，或直接用一氧化碳抑制这些酶，可以消除人血浆中纤维蛋白原溶解蛇毒金属蛋白酶的抗凝血作用。为了解释这些发现，我们选择兔作为Crotalus atrox毒液中毒的模型进行评估。通过血栓造形术确定，在体内引起凝血功能障碍，可能是由于毒液与血细胞结合并迅速从血液循环中清除所致，其浓度需要达到体外血浆中凝血功能障碍浓度的15倍。与人血浆不同，经Fe/CO预处理的兔血浆不受蛇毒纤维蛋白原溶解的保护。因此，在给兔注射毒液之前，需要给纯化的人纤维蛋白原（含或不含Fe/CO）。更有趣的是，暴露于一氧化碳的毒液在兔血浆中完全丧失了纤维蛋白原溶解作用，在全血中部分丧失了活性，这表明一氧化碳从毒液中脱离并与血红蛋白结合。因此，暴露于一氧化碳的毒液可以在全血中保持部分或完全抑制足够长的时间，以便从循环中清除，从而使兔子成为测试局部一氧化碳给药对咬伤部位有效性的有用模型。未来的研究计划在家兔中测试这些新方法来减轻毒液介导的凝血病。
Several in vitro investigations have demonstrated that anticoagulant effects of fibrinogenolytic snake venom metalloproteinases have been abrogated in human plasma by modifying fibrinogen with iron (Fe) and carbon monoxide (CO) to prevent catalysis or by directly inhibiting these enzymes with CO. In order to translate these findings, we chose to assess the rabbit as a model of envenomation with Crotalus atrox venom. It was determined with thrombelastography that 15-fold the concentration of venom noted to compromise coagulation in plasma in vitro was required to cause coagulopathy in vivo, likely secondary to venom binding to blood cells and being cleared from the circulation rapidly. Unlike human plasma, rabbit plasma pretreated with Fe/CO was not protected from fibrinogenolysis by venom. Consequently, the administration of purified human fibrinogen (with or without Fe/CO) would be required before venom administration to rabbits. Of greater interest, venom exposed to CO had complete loss of fibrinogenolytic effect in rabbit plasma and partial loss of activity in whole blood, indicative of unbinding of CO from venom and binding to hemoglobin. Thus, venom exposed to CO could remain partially or completely inhibited in whole blood long enough for clearance from the circulation, allowing rabbits to be a useful model to test the efficacy of regional CO administration to the bite site. Future investigations are planned to test these novel approaches to attenuate venom-mediated coagulopathy in the rabbit.
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影响因子：
4
作者：
Nielsen, Vance G.;Bazzell, Charles M.
通讯作者：
Bazzell, Charles M.
影响因子：
20.3
作者：
Chang, MC;Lin, HK;Huang, TF
通讯作者：
Huang, TF
DOI：
10.1006/bbrc.1994.1861
发表时间：
1994-06-30
影响因子：
3.1
作者：
HUNG, CC;CHIOU, SH
通讯作者：
CHIOU, SH
影响因子：
5.8
作者：
MARKS, BH;OBERER, D
通讯作者：
OBERER, D
影响因子：
1.1
作者：
Nielsen, Vance G.;Redford, Daniel T.;Boyle, Patrick K.
通讯作者：
Boyle, Patrick K.