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斜纹枯叶蛾毛虫毒液会增加大鼠血脑屏障的通透性。

Lonomia obliqua caterpillar venom increases permeability of the blood-brain barrier in rats.

作者信息

da Silva Gustavo Henrique, Hyslop Stephen, Alice da Cruz-Höfling Maria

机构信息

Departamento de Farmacologia, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, CP 6111, Campinas, SP 13083-970, Brazil.

出版信息

Toxicon. 2004 Nov;44(6):625-34. doi: 10.1016/j.toxicon.2004.07.016.

Abstract

Human envenoming by caterpillars of the saturniid moth Lonomia obliqua in southern Brazil produces a mild local response (erythema, some edema, and pain) and systemic effects that include incoagulable blood, renal failure and in severe accidents intracerebral hemorrhage. In this work, we used light and electron microscopy to investigate the morphological alterations in the brain and blood-brain barrier of rats injected intravenously with venom from L. obliqua spicules (200 microg/kg). Five semi-purified fractions of venom (200 microg/kg each) were also assayed. Quantitative morphological and ultrastructural analyses were done 6, 18, 24 and 72 h after the i.v. injection of venom and its fractions. Light microscopy showed that 6h after envenoming there was cerebellar edema, which decreased by 72 h. Intracerebral hemorrhage occurred in only one rat 24h after the injection of venom. Blood-brain barrier (BBB) breakdown, assessed by transmission electron microscopy based on the passage of an extracellular tracer (lanthanum nitrate) between brain capillary endothelial cells, was observed in the cerebellum and hippocampus 18 h after venom injection. At this time, the cerebellum was more sensitive to the venom than the hippocampus, as shown by the greater number of leaky vessels. The number of capillaries showing breakdown was lower after 72 h than after 18 h. None of the semi-purified fractions significantly increased the number of leaky vessels. These results indicate that L. obliqua caterpillar venom has a deleterious action on the rat BBB. The lack of effect of the venom fractions when administered alone suggested that a synergistic action of venom components may be responsible for the damage seen in the central nervous system, but this was not confirmed when three combinations of the fractions were tested.

摘要

在巴西南部,被天蚕蛾属的斜纹天蛾毛虫蜇伤的人会出现轻微的局部反应(红斑、些许水肿和疼痛)以及全身症状,包括血液无法凝固、肾衰竭,在严重的情况下还会出现脑出血。在这项研究中,我们使用光学显微镜和电子显微镜来研究静脉注射斜纹天蛾毒刺毒液(200微克/千克)的大鼠大脑和血脑屏障的形态学变化。我们还检测了毒液的五个半纯化组分(各200微克/千克)。在静脉注射毒液及其组分后的6、18、24和72小时进行了定量形态学和超微结构分析。光学显微镜显示,蜇伤后6小时出现小脑水肿,72小时时水肿减轻。仅一只大鼠在注射毒液24小时后出现脑出血。通过基于细胞外示踪剂(硝酸镧)在脑毛细血管内皮细胞之间的通过情况进行透射电子显微镜评估,发现毒液注射18小时后在小脑和海马体中观察到血脑屏障(BBB)破坏。此时,如渗漏血管数量更多所示,小脑比海马体对毒液更敏感。72小时后显示破坏的毛细血管数量比18小时后少。没有一个半纯化组分能显著增加渗漏血管的数量。这些结果表明斜纹天蛾毛虫毒液对大鼠血脑屏障有有害作用。单独给药时毒液组分没有效果,这表明毒液成分的协同作用可能是中枢神经系统中所见损伤的原因,但在测试组分的三种组合时并未得到证实。

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