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Abstract：
OBJECTIVE: Accidental contact with the Lonomia obliqua caterpillar is a common event in southern Brazil. Envenomed victims present consumption coagulopathy, which can evolve to acute kidney injury (AKI). In the present study, we searched for AKI biomarkers and changes in molecular pathway signatures through urine proteomic analysis.
METHODS: Male Wistar rats were injected with L. obliqua venom (1.5 mg/kg, via s.c.) or 0.9 % NaCl and distributed into metabolic cages. After 24 h, urine was obtained, and the set of differentially regulated proteins was analyzed by MudPIT technology in an OrbiTRAP mass spectrometer.
RESULTS: L. obliqua venom leads to an increase in urine output and water and electrolyte excretion and to an increase in the albumin to creatine ratio in urine. The proteomic analysis revealed an up-regulation of tubular injury biomarkers, such as neutrophil-gelatinase associated lipocalin (NGAL) and cystatin C, in urine from envenomed rats. Several components related to the heme scavenging system were up-regulated or exclusively identified in urine from envenomed animals. There was an increase in urinary heme levels and hemoglobin subunits, hemopexin, haptoglobin, and biliverdin reductase. Similarly, kinin- and angiotensin-generating/degrading peptidases, such as kallikreins, neprilysin, plasmin, dipeptidyl peptidase IV, cathepsin D, kininogen, and neutral, basic, glutamyl, and acidic aminopeptidases, were also up-regulated in urine.
CONCLUSIONS: L. obliqua envenomation induced tubular and glomerular injury, probably involving heme/hemoglobin toxicity and an imbalance in the kinin/angiotensin generating/degrading system.
METHODS: Male Wistar rats were injected with L. obliqua venom (1.5 mg/kg, via s.c.) or 0.9 % NaCl and distributed into metabolic cages. After 24 h, urine was obtained, and the set of differentially regulated proteins was analyzed by MudPIT technology in an OrbiTRAP mass spectrometer.
RESULTS: L. obliqua venom leads to an increase in urine output and water and electrolyte excretion and to an increase in the albumin to creatine ratio in urine. The proteomic analysis revealed an up-regulation of tubular injury biomarkers, such as neutrophil-gelatinase associated lipocalin (NGAL) and cystatin C, in urine from envenomed rats. Several components related to the heme scavenging system were up-regulated or exclusively identified in urine from envenomed animals. There was an increase in urinary heme levels and hemoglobin subunits, hemopexin, haptoglobin, and biliverdin reductase. Similarly, kinin- and angiotensin-generating/degrading peptidases, such as kallikreins, neprilysin, plasmin, dipeptidyl peptidase IV, cathepsin D, kininogen, and neutral, basic, glutamyl, and acidic aminopeptidases, were also up-regulated in urine.
CONCLUSIONS: L. obliqua envenomation induced tubular and glomerular injury, probably involving heme/hemoglobin toxicity and an imbalance in the kinin/angiotensin generating/degrading system.
摘要：
目的：与Lonomia斜纹毛虫的意外接触是巴西南部的常见事件。Envenomed受害者表现出消耗凝血病，可演变为急性肾损伤（AKI）。在本研究中,我们通过尿蛋白组分析搜索了AKI生物标志物和分子途径特征的变化.
方法：雄性Wistar大鼠注射斜血乳杆菌毒（1.5mg/kg，通过s.c.)或0.9%NaCl分配到代谢笼中。24小时后，获得尿液，并通过MudPIT技术在OrbiTRAP质谱仪中分析差异调节的蛋白质组。
结果：L.斜毒液导致尿量增加，水和电解质排泄增加，尿液中白蛋白与肌酸的比率增加。蛋白质组学分析揭示了肾小管损伤生物标志物的上调，如中性粒细胞明胶酶相关脂质运载蛋白（NGAL）和胱抑素C，在毒蛇老鼠的尿液中。与血红素清除系统相关的几种成分在静脉动物的尿液中被上调或专门鉴定。尿血红素水平和血红蛋白亚单位增加，血红素结合蛋白,触珠蛋白，和胆绿素还原酶。同样，激肽和血管紧张素生成/降解肽酶，如激肽释放酶，Neprilysin,纤溶酶,二肽基肽酶IV，组织蛋白酶D,激肽原,中立,基本的，谷氨酰,和酸性氨肽酶，在尿液中也上调。
结论：L.斜毒液引起肾小管和肾小球损伤，可能涉及血红素/血红蛋白毒性和激肽/血管紧张素生成/降解系统的失衡。
方法：雄性Wistar大鼠注射斜血乳杆菌毒（1.5mg/kg，通过s.c.)或0.9%NaCl分配到代谢笼中。24小时后，获得尿液，并通过MudPIT技术在OrbiTRAP质谱仪中分析差异调节的蛋白质组。
结果：L.斜毒液导致尿量增加，水和电解质排泄增加，尿液中白蛋白与肌酸的比率增加。蛋白质组学分析揭示了肾小管损伤生物标志物的上调，如中性粒细胞明胶酶相关脂质运载蛋白（NGAL）和胱抑素C，在毒蛇老鼠的尿液中。与血红素清除系统相关的几种成分在静脉动物的尿液中被上调或专门鉴定。尿血红素水平和血红蛋白亚单位增加，血红素结合蛋白,触珠蛋白，和胆绿素还原酶。同样，激肽和血管紧张素生成/降解肽酶，如激肽释放酶，Neprilysin,纤溶酶,二肽基肽酶IV，组织蛋白酶D,激肽原,中立,基本的，谷氨酰,和酸性氨肽酶，在尿液中也上调。
结论：L.斜毒液引起肾小管和肾小球损伤，可能涉及血红素/血红蛋白毒性和激肽/血管紧张素生成/降解系统的失衡。
