Abstract：
Naja naja snake bite causes thousands of deaths worldwide in a year. N. naja envenomed victims exhibit both local and systemic reactions that potentially lead to death. In clinical practice, pulmonary complications in N. naja envenomation are commonly encountered. However, the molecular mechanisms underlying N. naja venom-induced lung toxicity remain unknown. Here, we reasoned that N. naja venom-induced lung toxicity is prompted by NLRP3 inflammasome and MAPKs activation in mice. Treatment with dimethyl ester of bilirubin (BD1), significantly inhibited the N. naja venom-induced activation of NLRP3 inflammasome and MAPKs both in vivo and in vitro (p < 0.05). Further, BD1 reduced N. naja venom-induced recruitment of inflammatory cells, and hemorrhage in the lung toxicity examined by histopathology. BD1 also diminished N. naja venom-induced local toxicities in paw edema and myotoxicity in mice. Furthermore, BD1 was able to enhance the survival time against N. naja venom-induced mortality in mice. In conclusion, the present data showed that BD1 alleviated N. naja venom-induced lung toxicity by inhibiting NLRP3 inflammasome and MAPKs activation. Small molecule inhibitors that intervene in venom-induced toxicities may have therapeutic applications complementing anti-snake venom.
摘要：
Najanaja蛇咬在一年内导致全球数千人死亡。N.najaenvenomed受害者表现出可能导致死亡的局部和系统性反应。在临床实践中,N.眼镜蛇的肺部并发症是常见的。然而,眼镜蛇毒诱导肺毒性的分子机制尚不清楚.这里,我们认为眼镜蛇毒诱导的肺毒性是由小鼠NLRP3炎性体和MAPK激活引起的。用胆红素二甲酯（BD1）治疗，在体内和体外均显着抑制了眼镜蛇毒诱导的NLRP3炎性体和MAPK的激活（p<0.05）。Further,BD1减少眼镜蛇毒液诱导的炎症细胞募集，和组织病理学检查的肺毒性出血。BD1还减少了眼镜蛇毒在小鼠爪水肿和肌毒性中引起的局部毒性。此外，BD1能够增强小鼠的生存时间，以对抗眼镜蛇毒诱导的死亡率。总之,目前的数据表明，BD1通过抑制NLRP3炎性体和MAPK的激活减轻了眼镜蛇毒引起的肺毒性。干预毒液诱导毒性的小分子抑制剂可能具有补充抗蛇毒的治疗应用。
