[1]李桂林,邓琳,罗金英,等.铁死亡在新生大鼠高胆红素血症脑损伤中的作用[J].福建医药杂志,2023,45(04):97-101.
　LI Guilin,DENG Lin,LUO Jinying,et al.Role of ferroptosis in hyperbilirubinemia induced brain injury in neonatal rats[J].FUJIAN MEDICAL JOURNAL,2023,45(04):97-101.
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铁死亡在新生大鼠高胆红素血症脑损伤中的作用()
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《福建医药杂志》[ISSN:1002-2600/CN:35-1071/R]

卷:
45
期数:
2023年04期
页码:
97-101
栏目:
基础研究
出版日期:
2023-08-15

文章信息/Info

Title:
Role of ferroptosis in hyperbilirubinemia induced brain injury in neonatal rats
文章编号:
1002-2600(2023)04-0097-05
作者:
李桂林; 邓琳; 罗金英; 周进福1
福建省妇幼保健院 福建医科大学妇儿临床医学院(福州 350003)
Author(s):
LI Guilin;  DENG Lin;  LUO Jinying;  ZHOU Jinfu
Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian 350001, China
关键词:
高胆红素血症;  脑损伤;  铁死亡;  ACSL4
Keywords:
hyperbilirubinemia;  brain injury;  ferroptosis;  ACSL4
分类号:
R332; R722
文献标志码:
A
摘要:
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。
Abstract:
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.

参考文献/References:

[1] Greco C,Arnolda G,Boo N Y,et al.Neonatal jaundice in low-and middle-income countries:lessons and future directions from the 2015 don ostrow trieste yellow retreat[J].Neonatology,2016,110(3):172-180.
[2] Brito M A,Rosa A I,Falcão A S,et al.Unconjugated bilirubin differentially affects the redox status of neuronal and astroglial cells[J].Neurobiology of Disease,2008,29(1):30-40.
[3] Pazar A,Kolgazi M,Memisoglu A,et al.The neuroprotective and anti-apoptotic effects of melatonin on hemolytic hyperbilirubinemia-induced oxidative brain damage[J].Journal of Pineal Research,2016,60(1):74-83.
[4] Luo Y,Peng M,Wei H.Melatonin promotes brain-derived neurotrophic factor(BDNF)expression and anti-apoptotic effects in neonatal hemolytic hyperbilirubinemia via a phospholipase(PLC)- mediated mechanism[J].Medical Science Monitor,2017(23):5951-5959.
[5] Wang C Y,Chen S S,Guo H Y,et al.Forsythoside a mitigates alzheimer's-like pathology by inhibiting ferroptosis-mediated neuroinflammation via Nrf2/GPX4 axis activation[J].International Journal of Biological Sciences,2022,18(5):2075-2090.
[6] Thapa K,Khan H,Kanojia N,et al.Therapeutic insights on ferroptosis in parkinson's disease[J].European Journal of Pharmacology,2022(930):175133.
[7] Ren S,Chen Y,Wang L K,et al.Neuronal ferroptosis after intracerebral hemorrhage[J].Frontiers in Molecular Biosciences,2022,9:966478.
[8] Cui Y,Zhang Y,Zhao X L,et al.ACSL4 exacerbates ischemic stroke by promoting ferroptosis-induced brain injury and neuroinflammation[J].Brain,Behavior,and Immunity,2021(93):312-321.
[9] Mejia G B,Sanz C R,Avila M M,et al.Experimental hemolysis model to study bilirubin encephalopathy in rat brain[J].Journal of Neuroscience Methods,2008,168(1):35-41.
[10] Roger C,Koziel V,Vert P,et al.Autoradiographic mapping of local cerebral permeability to bilirubin in immature rats:effects of hyperbilirubinemia[J].Pediatric Research,1996,39(1):64-71.
[11] Arnason S,Molewijk K,Henningsson A J,et al.Brain damage markers neuron-specific enolase(NSE)and S100B in serum in children with Lyme neuroborreliosis—detection and evaluation as prognostic biomarkers for clinical outcome[J].European Journal of Clinical Microbiology and Infectious Diseases,2022,41(7):1051-1057.
[12] 杨李,王宝田,田克印,等.溶血致新生大鼠高胆红素血症动物模型的建立及评价[J].中国实验动物学报,2015,23(4):371-374.
[13] Doll S,Freitas F P,Shah R,et al.FSP1 is a glutathione-independent ferroptosis suppressor[J].Nature,2019,575(7784):693-698.
[14] Bersuker K,Hendricks J M,Li Z,et al.The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis[J].Nature,2019,575(7784):688-692.
[15] Reed A,Ichu T A,Milosevich N,et al.LPCAT3 inhibitors remodel the polyunsaturated phospholipid content of human cells and protect from ferroptosis[J].ACS Chemical Biology,2022,17(6):1607-1618.
[16] Yan W C,Wang D X,Wan N,et al.Living cell-target responsive accessibility profiling reveals silibinin targeting ACSL4 for combating ferroptosis[J].Analytical Chemistry,2022,94(43):14820-14826.
[17] Qu X F,Liang T Y,Wu D G,et al.Acyl-CoA synthetase long chain family member 4 plays detrimental role in early brain injury after subarachnoid hemorrhage in rats by inducing ferroptosis[J].CNS Neuroscience and Therapeutics,2021,27(4):449-463.

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备注/Memo

备注/Memo:
基金项目:福建省自然科学基金面上项目(2020J01327); 福建省卫生健康委中青年骨干人才培养项目(2020GGB017)
1 通信作者,Email:zhou811203@fjmu.edu.cn
更新日期/Last Update: 2023-08-15