铁死亡在新生大鼠高胆红素血症脑损伤中的作用

Role of ferroptosis in hyperbilirubinemia induced brain injury in neonatal rats

目的 探究铁死亡在新生大鼠高胆红素血症脑损伤中的作用。方法 通过腹腔注射盐酸苯肼构建高胆红素血症脑损伤动物模型,应用铁死亡抑制剂及铁鳌合剂去铁胺干预,检测神经元特异性烯醇化酶(NSE)、S100钙结合蛋白B(S100B)、脑组织铁、氧化应激损伤、铁死亡生化指标和铁死亡通路的关键蛋白。结果 与对照组相比,实验组血清脑损伤分子标志物NSE和S100B水平明显升高、脑组织氧化应激及铁死亡生化指标GSH水平下降、MDA水平升高、组织铁水平升高和SOD活性降低,差异具有统计学意义(P<0.05),在应用去铁胺干预后,可逆转上述指标的改变。与对照组相比,实验组铁死亡通路的关键蛋白ACSL4表达上调,而FSP1表达下调,GPX4在实验组中表达上调,差异具有统计学意义(P<0.05),DFO干预后可逆转上述改变。结论 铁死亡参与新生高胆红素血症大鼠脑损伤,为胆红素神经毒性机制研究提供新思路,但其具体机制有待于进一步阐明。

Objective To explore the role of ferroptosis in hyperbilirubinemia induced brain injury in neonatal rats.Methods An animal model of hyperbilirubinemia induced brain injury was established by intraperitoneal injection of phenylhydrazine hydrochloride.An animal model of hyperbilirubinemia was intervented with deferoxamine,which was known as ferroptosis inhibitors and iron chelation.NSE,S100B,tissue iron,biochemical indicators and key proteins of pathway of ferroptosis were determined.Results Compared with the control group,the serum levels of NSE and S100 B,which were the markers of brain injury,increased in the experimental group(P<0.05).Compared with the control group,the level of GSH decreased,MDA increased,SOD activity decreased,and tissue iron increased in the experimental group(P<0.05).Western blot results showed that compared with the control group,the expression protein of ACSL4 and GPX4 increased in the brain tissue of the rats in the experimental group,while the expression protein of FSP1 decreased(P<0.05).DFO intervention could partially or completely reverse the changes of the above biomarker in rats with hyperbilirubinemia induced brain injury.Conclusion Ferroptosis is involved in hyperbilirubinemia induced brain injury in neonatal rats,which provids a new idea for the mechanism of bilirubin neurotoxicity.However,the specific mechanism of ferroptosis participated in bilirubin neurotoxicity needs to be further clarified.