Hypoxia aggravates propofol-induced hippocampal neuron injury in immature SD rats through ferroptosis

Wen GAO; Weiping WANG; Ling LIU; Fei YANG; Shengfen TU

doi:10.16016/j.2097-0927.202208021

您当前的位置：

首页 >

文章列表页 >

Hypoxia aggravates propofol-induced hippocampal neuron injury in immature SD rats through ferroptosis

Neurosciences | 更新时间：2026-01-09

- Hypoxia aggravates propofol-induced hippocampal neuron injury in immature SD rats through ferroptosis
- Journal of Army Medical University Vol. 45, Issue 5, Pages: 380-385(2023)
- 作者机构：
  
  400014 重庆，重庆医科大学附属儿童医院麻醉科，国家儿童健康与疾病临床医学研究中心，儿童发育疾病研究教育部重点实验室，儿科学重庆市重点实验室
- 作者简介：
- 基金信息：
  
  the National Natural Science Foundation for Young Scholars of China(31200853)
- DOI：10.16016/j.2097-0927.202208021
  CLC： R322.81;R965.3;R971.2
- Received：02 August 2022，
  
  Revised：2022-10-19，
  
  Published：15 March 2023
- 稿件说明：
移动端阅览
Wen GAO, Weiping WANG, Ling LIU, et al. Hypoxia aggravates propofol-induced hippocampal neuron injury in immature SD rats through ferroptosis[J]. Journal of Army Medical University, 2023, 45(5): 380-385.
DOI：

Wen GAO, Weiping WANG, Ling LIU, et al. Hypoxia aggravates propofol-induced hippocampal neuron injury in immature SD rats through ferroptosis[J]. Journal of Army Medical University, 2023, 45(5): 380-385. DOI： 10.16016/j.2097-0927.202208021.

摘要

目的

探讨低氧复合丙泊酚通过铁死亡对未成熟SD大鼠海马神经元的影响。

方法

将168只新生7 d龄SD大鼠(雌雄各半)按随机数表法分为6组[

=28

体质量(15.59±1.13) g

]

: 脂肪乳氧气组(CO)、脂肪乳空气组(CA)、脂肪乳低氧组(CH)、丙泊酚氧气组(PO)、丙泊酚空气组(PA)、丙泊酚低氧组(PH)。丙泊酚组腹腔注射丙泊酚50 mg/kg、脂肪乳组腹腔注射脂肪乳剂5 mL/kg

1次/d

连续7 d。每次注射完毕后分别放入氧浓度为50%、21%、18%的暖箱(38℃)

待翻正反射恢复后

即放回常氧环境中由母鼠继续喂养。观察并监测未成熟SD大鼠丙泊酚麻醉后呼吸频率(RR)和血氧饱和度(SpO

); 透射电镜观察海马神经元内线粒体形态改变; 生化法检测海马组织中Fe

、丙二醛(malondialdehyde

MDA)含量

Western blot检测海马组织中转铁蛋白受体(transferrin receptor

TFRC)的蛋白表达。

结果

RR和SpO

监测结果显示: 与相应的脂肪乳组比较

PO组仅RR降低(

0.01)

而PA组、PH组RR和SpO

均降低(

0.01)。透射电镜显示: PA组、PH组海马神经元内线粒体普遍肿胀

线粒体嵴溶解、消失。生化法检测结果显示: 与相应的脂肪乳组比较

PO组、PA组、PH组Fe

含量、MDA水平均升高(

0.01);与PO组比较

PA组、PH组Fe

含量、MDA水平均升高(

0.05)。Western blot检测结果显示: 与相应的脂肪乳组比较

PO组、PA组、PH组

TFRC表达上调(

0.05);与PO组比较

PA组、PH组的TFRC表达上调(

0.05)。

结论

低氧因素增加丙泊酚对未成熟SD大鼠海马神经元的损伤

其机制与海马组织铁死亡相关。

Abstract

Objective

To investigate the effect of hypoxia combined with propofol on immature Sprague-Dawley (SD) rat hippocampal neurons through ferroptosis.

Methods

A total of 168 7-day-old SD rats (half male and half female

15.59±1.13 g) were randomly divided into 6 groups (

=28): lipid emulsion solvent+50% oxygen (CO)

lipid emulsion solvent+air (CA)

lipid emulsion solvent+18% oxygen (CH)

propofol+50% oxygen (PO)

propofol+air (PA)

and propofol+18% oxygen (PH) groups.The rats in the propofol group were intraperitoneally injected with 50 mg/kg propofol

and those in the lipid emulsion group were intraperitoneally injected with 5 mL/kg lipid emulsion

once a day for 7 consecutive days.After injection

the mice were put into warm chambers with oxygen concentration of 50%

21% and 18%(38℃) respectively.After the righting reflex recovered

the mice were immediately put back into the normoxic environment for feeding by their mothers.The respiratory rate (RR) and blood oxygen saturation (SpO

) of immature SD rats were observed and monitored after propofol anesthesia.The morphological changes of mitochondria in hippocampal neurons were observed by transmission electron microscopy.The contents of Fe

and malondialdehyde (MDA) in the hippocampus were detected by biochemical assay

and the protein expression of transferrin receptor (TFRC) in the hippocampus was detected by Western blotting.

Results

The results of RR and SpO

monitoring showed that compared with the corresponding lipid emulsion group

only RR in the PO group was decreased (CO

0.01)

while RR and SpO

in the PA and PH

groups were decreased (CA

s PA

0.01).Transmission electron microscopy displayed that the mitochondria in the hippocampal neurons of the PA and PH groups were generally swollen

with dissolved and disappeared mitochondrial cristae.The results of the biochemical assay showed that the Fe

content and MDA level in the PO

and PH groups were increased than those in the corresponding lipid emulsion groups (

0.01).Compared with the PO group

the content of Fe

and MDA were increased in the PA and PH groups (

0.05).Western blotting indicated that compared with the corresponding lipid emulsion group

the expression level of TFRC in the PO

and PH groups was increased (

0.05)

while the level was increased in the PA and PH groups than the PO group (

0.05).

Conclusion

Hypoxia aggravates the damage of hippocampal neurons induced by propofol in immature SD rats

and the mechanism is related to the ferroptosis of hippocampal tissue.

关键词

Keywords

references

CHIDAMBARAN V, COSTANDI A, D'MELLO A. Propofol: a review of its role in pediatric anesthesia and sedation[J]. CNS Drugs, 2015, 29(7): 543-563. DOI: 10.1007/s40263-015-0259-6.

VAN SCHAIK E P C, BLANKMAN P, VAN KLEI W A, et al . Hypoxemia during procedural sedation in adult patients: a retrospective observational study[J ] . Can J Anaesth, 2021, 68(9): 1349-1357. DOI: 10.1007/s12630-021-01992-6.

张敬, 于晴, 刘阳, 等. 丙泊酚合并低氧通过p38通路损伤未成熟大鼠的认知功能[J]. 南方医科大学学报, 2018, 38(11): 1294-1299. DOI: 10.12122/j.issn.1673-4254.2018.11.03.

ZHANG J, YU Q, LIU Y, et al . Propofol combined with hypoxia induces c ognitive dysfunction in immature rats via p38 pathway[J ] . J South Med Univ, 2018, 38(11): 1294-1299. DOI: 10.12122/j.issn.1673-4254.2018.11.03..

于晴, 刘阳, 孙茫, 等. 低氧因素对丙泊酚麻醉新生大鼠认知功能的影响[J]. 中国临床药理学杂志, 2018, 34(14): 1678-1681. DOI: 10.13699/j.cnki.1001-6821.2018.14.027.

YU Q, LIU Y, SUN M, et al . Effect of hypoxic factors on cognitive function in propofol-anesthetized neonatal rats[J ] . Chin J Clin Pharmacol, 2018, 34(14): 1678-1681. DOI: 10.13699/j.cnki.1001-6821.2018.14.027.

SUN M, YUAN R X, LIU H, et al . The effects of repeated propofol anesthesia on spatial memory and long-term potentiation in infant rats under hypoxic conditions[J ] . Genes Dis, 2020, 7(2): 245-252. DOI: 10.1016/j.gendis.2019.02.001.

TANG D L, CHEN X, KANG R, et al . Ferroptosis: molecular mechanisms and health implications[J ] . Cell Res, 2021, 31(2): 107-125. DOI: 10.1038/s41422-020-00441-1.

LI J, CAO F, YIN H L, et al . Ferroptosis: past, present and future[J ] . Cell Death Dis, 2020, 11(2): 88. DOI: 10.1038/s41419-020-2298-2.

BLISS T V P, COLLINGRIDGE G L. A synaptic model of memory: long-term potentiation in the hippocampus[J]. Nature, 1993, 361(6407): 31-39. DOI: 10.1038/361031a0.

LIU P F, YUAN J, FENG Y T, et al . Ferroptosis contributes to isoflurane-induced neurotoxicity and learning and memory impairment[J ] . Cell Death Discov, 2021, 7(1): 72. DOI: 10.1038/s41420-021-00454-8.

KAHRAMAN S, ZUP S L, MCCARTHY M M, et al . GABAergic mechanism of propofol toxicity in immature neurons[J ] . J Neurosurg Anesthesiol, 2008, 20(4): 233-240. DOI: 10.1097/ANA.0b013e31817ec34d.

HUANG J, JING S, CHEN X, et al . Propofol administration during early postnatal life suppresses hippocampal neurogenesis[J ] . Mol Neurobiol, 2016, 53(2): 1031-1044. DOI: 10.1007/s12035-014-9052-7.

CATTANO D, YOUNG C, STRAIKO M M, et al . Subanesthetic doses of propofol induce neuroapoptosis in the infant mouse brain[J ] . Anesth Analg, 2008, 106(6): 1712-1714. DOI: 10.1213/ane.0b013e318172ba0a.

LEE T L. Pharmacology of propofol[J]. Ann Acad Med Singap, 1991, 20(1): 61-65.

TU S F, WANG X Y, YANG F, et al . Propofol induces neuronal apoptosis in infant rat brain under hypoxic conditions[J ] . Brain Res Bull, 2011, 86(1/2): 29-35. DOI: 10.1016/j.brainresbull.2011.06.017.

孙茫, 沈炼桔, 刘阳, 等. 低氧环境下丙泊酚可增加PC12细胞的凋亡[J]. 南方医科大学学报, 2017, 37(2): 216-220. DOI: 10.3969/j.issn.1673-4254.2017.02.12.

SUN M, SHEN L J, LIU Y, et al . Effect of propofol on apoptosis of PC12 cells under hypoxic condition and the mechanism[J ] . J South Med Univ, 2017, 37(2): 216-220. DOI: 10.3969/j.issn.1673-4254.2017.02.12.

胡淼, 门运政, 陈蕾, 等. 右美托咪定通过抑制铁死亡发挥对小鼠脑缺血再灌注损伤的保护作用[J]. 中南大学学报(医学版), 2022, 47(5): 600-609.

HU M, MEN Y Z, CHEN L, et al . Dexmedetomidine exerts its protective effect on cerebral ischemia reperfusion injury in mice by inhibiting ferroptosis[J ] . J Central South Univ Med Sci, 2022, 47(5): 600-609.

董小铷, 张向楠, 李丹, 等. 红景天苷对低压低氧诱发大鼠脑损伤的保护作用[J]. 细胞与分子免疫学杂志, 2015, 31(10): 1327-1331. DOI: 10.13423/j.cnki.cjcmi.007573.

DONG X R, ZHANG X N, LI D, et al . Protective effect of salidroside against high altitude hypoxia-induced brain injury in rats[J ] . Chin J Cell Mol Immunol, 2015, 31(10): 1327-1331. D OI: 10.13423/j.cnki.cjcmi.007573.

阮俊勇, 雷涛, 董旭, 等. 急性低压低氧环境对脑功能及其结构影响的研究进展[J]. 中华物理医学与康复杂志, 2020, 42(9): 858-860. DOI: 10.3760/cma.j.issn.0254-1424.2020.09.022.

RUAN J Y, LEI T, DONG X, et al . Research progress on the effects of acute hypothermia and hypoxia on brain function and structure[J ] . Chin J Phys Med Rehabil, 2020, 42(9): 858-860. DOI: 10.3760/cma.j.issn.0254-1424.2020.09.022.

MASALDAN S, BUSH A I, DEVOS D, et al . Striking while the iron is hot: iron metabolism and ferroptosis in neurodegeneration[J ] . Free Radic Biol Med, 2019, 133: 221-233. DOI: 10.1016/j.freeradbiomed.2018.09.033.

XUAN W T, LU X Y, YANG Z Y, et al . Propofol protects against erastin-induced ferroptosis in HT-22 cells[J ] . J Mol Neurosci, 2022, 72(9): 1797-1808. DOI: 10.1007/s12031-022-02017-7.

李正民, 张玉明, 张振, 等. HIF-1介导的线粒体能量代谢参与丙泊酚调控肾透明细胞癌细胞增殖及凋亡[J]. 国际肿瘤学杂志, 2019, 46(12): 711-717. DOI: 10.3760/cma.j.issn.1673-422X.2019.12.002.

LI Z M, ZHANG Y M, ZHANG Z, et al . Mitochondrial energy metabolism mediated via HIF-1 involves the proliferation and apoptosis of renal clear cell carcinoma cells regulated by propofol[J ] . J Int O ncol, 2019, 46(12): 711-717. DOI:10.3760/cma.j.issn.1673-422X.2019.12.002..

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Mdivi-1 improves cognitive dysfunction in immature SD rats induced by hypoxia combined with propofol by inhibiting excessive mitophagy

Role of parthanatos in PC12 cell injury induced by propofol combined with hypoxic conditions

Chronic hypoxia reduces cold tolerance via hepatic ANGPTL3-driven mitochondrial damage and adipose thermogenesis suppression

Dimethyl fumarate alleviates high-altitude hypoxic acute lung injury by activating the NRF2/SLC7A11 axis to inhibit pulmonary epithelial ferroptosis and regulate macrophage polarization

Accessible chromatin upregulates circadian rhythm transcription factor NPAS2 to promote Ferroptosis Resistance in Gastric Cancer Cells

Related Author

XU Yao

YANG Shun

YANG Fei

YANG Ying

YUN Huanjie

TAUSEEF Ahmad

TU Shengfen

Weiping WANG

Related Institution

Department of Anesthesiology Children’s Hospital of Chongqing Medical University， National Clinical Research Center for Child Health and Disorders， Ministry of Education Key Laboratory of Child Development and Disorders， Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders

Department of Anesthesiology, National Clinical Research Center of Child Health and Disease, Key Laboratory of Child Developmental Diseases of Ministry of Education, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University

Department of Clinical Nursing, School of Nursing， Army Medical University （Third Military Medical University）

Department of Frigid Zone Medicine， College of High Altitude Military Medicine, School of Nursing， Army Medical University （Third Military Medical University）

Key Laboratory of Extreme Environmental Medicine of Ministry of Education, School of Nursing， Army Medical University （Third Military Medical University）

⁰