小胶质细胞铁死亡在烟雾吸入性脑损伤中的作用机制探讨

doi:10.11958/20231628

天津医药 ›› 2024, Vol. 52 ›› Issue (8): 791-797.doi: 10.11958/20231628

小胶质细胞铁死亡在烟雾吸入性脑损伤中的作用机制探讨

刘斌¹^,²(), 杨龙¹, 李文莉³, 邵宁宁⁴, 董津睿⁵^,^△()

1 天津大学融合医学中心（邮编300162）
2 中国人民武装警察部队特色医学中心感染性疾病科
3 天津大学医学院应急研究院
4 天津大学海河医院基础科研部
5 天津大学医学院医学工程与转化医学研究院

收稿日期:2023-11-03 修回日期:2024-03-25 出版日期:2024-08-15 发布日期:2024-08-16
通讯作者: △E-mail：jinrui_dong@tju.edu.cn
作者简介:刘斌（1976），女，副主任医师，主要从事器官损伤修复方面研究。E-mail：iamicehe@163.com
基金资助:
国家自然科学基金资助项目(82200655);天津市自然科学基金项目(22JCYBJC00730)

Mechanism of microglia ferroptosis in smoke inhalation-induced brain injury

LIU Bin¹^,²(), YANG Long¹, LI Wenli³, SHAO Ningning⁴, DONG Jinrui⁵^,^△()

1 Center for Integrative Medicine, Tianjin University, Tianjin 300162, China
2 Department of Infectious Diseases, Characteristic Medical Center of Chinese People's Armed Police Force
3 Institute of Emergency Medicine, Tianjin University School of Medicine
4 Department of Basic Science and Research, Haihe Hospital, Tianjin University
5 Institute of Medical Engineering and Translational Medicine, Tianjin University School of Medicine

Received:2023-11-03 Revised:2024-03-25 Published:2024-08-15 Online:2024-08-16
Contact: △E-mail：jinrui_dong@tju.edu.cn

刘斌, 杨龙, 李文莉, 邵宁宁, 董津睿. 小胶质细胞铁死亡在烟雾吸入性脑损伤中的作用机制探讨[J]. 天津医药, 2024, 52(8): 791-797.

LIU Bin, YANG Long, LI Wenli, SHAO Ningning, DONG Jinrui. Mechanism of microglia ferroptosis in smoke inhalation-induced brain injury[J]. Tianjin Medical Journal, 2024, 52(8): 791-797.

摘要/Abstract

摘要：

目的探究小胶质细胞铁死亡在烟雾吸入性脑损伤中的作用机制。方法将20只C57BL/6小鼠随机分为对照组（Control组）、烟雾吸入性损伤（SII）组、铁抑素治疗组（Fer-1组，2.5 mmol/kg Fer-1）、甲磺酸去铁胺治疗组（DFO组，200 mg/kg DFO），每组5只。Fer-1组和DFO组于造模后第1、3、5天分别腹腔注射Fer-1和DFO。第6天通过苏木素伊红（HE）染色、普鲁士蓝染色观察各组小鼠脑组织的病理变化。实时荧光定量逆转录PCR（RT-qPCR）检测脑损伤因子、炎性因子、铁死亡因子基因表达水平。双联吡啶比色法测定小鼠脑组织中铁含量。硫代巴比妥酸比色法测定小鼠脑组织脂质过氧化物（LPO）、丙二醛（MDA）含量。黄嘌呤氧化酶法测定小鼠脑组织超氧化物歧化酶（SOD）活性。二硫代二硝基苯甲酸（DTNB）直接法测定小鼠脑组织谷胱甘肽（GSH）含量。DMEM完全培养基培养BV2细胞，分为Control组、Erastin组（10 μmol/L Erastin刺激）、Fer-1组（10 μmol/L Erastin与5 mmol/L Fer-1同时刺激）、DFO组（10 μmol/L Erastin与50 mmol/L DFO同时刺激）。24 h后，CCK-8法检测细胞活力变化，流式细胞术检测细胞凋亡情况，2，7-二氯荧光素二乙酸酯（DCFDA）检测细胞内活性氧（ROS）水平，线粒体红色荧光探针检测线粒体膜电位。结果与Control组相比，SII组小鼠脑组织出现明显铁沉积和炎症反应，脑组织脑损伤因子、炎性因子mRNA表达水平升高，乙酰辅酶A合成酶长链家族4（ACSL4）、核受体共激活因子4（NCOA4）mRNA表达水平升高，谷胱甘肽氧化酶4（GPX4）、溶质载体家族7成员11（SLC7A11）mRNA表达水平降低，小鼠脑组织GSH和SOD含量降低，LPO和MDA含量升高（P<0.05）。与SII组相比，Fer-1组和DFO组小鼠相应指标变化与上述相反（P<0.05），小鼠脑组织损伤减轻。BV2细胞实验结果显示，与Control组相比，Erastin组BV2细胞存活率下降、凋亡率升高（P<0.05），细胞内ROS水平升高，线粒体膜电位下降；与Erastin组相比，Fer-1组、DFO组细胞相应指标变化与上述相反（P<0.05），BV2细胞氧化损伤得到缓解。结论铁死亡抑制剂Fer-1和DFO能够抑制小胶质细胞铁死亡并缓解烟雾吸入性脑损伤。

关键词: 烟雾吸入性损伤, 小神经胶质细胞, 铁死亡, 去铁胺, 铁抑素

Abstract:

Objective To investigate the underlying mechanism of microglia ferroptosis in smoke inhalation-induced (SII) brain injury. Methods Twenty SPF-grade male C57BL/6 mice were randomly divided into the control group, the SII group, the ferrostatin-1 group (Fer-1, 2.5 mmol/kg) and the deferoxamine group (DFO, 200 mg/kg), with 5 mice in each group. Mice in the Fer-1 group and the DFO group were intraperitoneally injected with Fer-1 and DFO 1, 3 and 5 day after smoke exposure, respectively. The pathological changes of brain tissue were examined by HE staining and Prussian blue staining on the 6th day after smoke exposure. RT-qPCR was used to detect levels of inflammatory factors, brain tissue damage markers and ferroptosis markers. The contents of iron in mouse brain tissue were determined by double pyridine colorimetric assay. The contents of malondialdehyde (MDA) and lipid peroxide (LPO) in mouse brain tissue were determined by thiobarbituric acid (TBA) colorimetric assay. Superoxide dismutase (SOD) activity in mouse brain tissue was measured by xanthine oxidase assay kit. The contents of glutathione (GSH) in mouse brain tissue were determined by direct method of dithiodinitrobenzoic acid (DTNB) assay. BV2 cells were cultured in complete DMEM medium and divided into the control group, the erastin group (10 μmol/L), the Fer-1 group (erastinc stimulation combined with 5 mmol/L Fer-1 treatment) and the DFO group (erastinc stimulation combined with 50 mmol/L DFO treatment). After 24 h, cell viability was detected by CCK-8 assay, cell apoptosis was detected by Annexin V-FITC/PI flow cytometry, intracellular reactive oxygen species (ROS) production was detected by DCFDA staining, and mitochondrial membrane potential was detected by MitoTracker Red CMXRos staining. Results Compared with the control group, enhanced iron deposition and inflammation in brain tissue, elevated mRNA expression of inflammatory markers and damage markers in brain tissue, up-regulated ACSL4 and NCOA4 mRNA levels, down-regulated GPX4 and SLC7A11 mRNA levels, decreased GSH and SOD contents, and increased LPO and MDA contents were observed in brain tissue of the SII group (P<0.05). The mRNA expression level of 7 member of solute carrier family 11 (SLC7A11) was decreased in mice of the SII group. The contents of GSH and SOD were decreased, and the contents of LPO and MDA were increased (P<0.05). Compared with the SII group, all the above parameters were reversed in the Fer-1 group and the DFO group, and the damage of mouse brain tissue was alleviated (P<0.05). In BV2 cell experiments, compared with the control group, decreased survival rate of BV2 cells and increased apoptosis rate were found in the erastin group (P<0.05), and increased intracellular ROS level and decreased mitochondrial membrane potential were also observed in the erastin-stimulated BV2 cells. The above parameters were opposite to those of the erastin group in the Fer-1 group and the DFO group (P<0.05), and the oxidative damage of BV2 cells was alleviated. Conclusion The ferroptosis inhibitors Fer-1 and DFO can inhibit microglia ferroptosis and alleviate smoke inhalation-induced brain injury.

Key words: smoke inhalation injury, microglia, ferroptosis, deferoxamine, ferrostatin-1

中图分类号:

R363.21，R644

图/表 9

参考文献 29

[1]	SONG M, LV Q, ZHANG X, et al. Dynamic tracking human mesenchymal stem cells tropism following smoke inhalation injury in NOD/SCID mice[J]. Stem Cells Int, 2016,2016:1691856. doi:10.1155/2016/1691856.
[2]	ZHANG H H, ZHOU X J, ZHONG Y S, et al. Naringin suppressed airway inflammation and ameliorated pulmonary endothelial hyperpermeability by upregulating Aquaporin1 in lipopolysaccharide/cigarette smoke-induced mice[J]. Biomed Pharmacother, 2022, 150:113035. doi:10.1016/j.biopha.2022.113035.
[3]	MURAKAMI K, TRABER D L. Pathophysiological basis of smoke inhalation injury[J]. News Physiol Sci, 2003, 18(3):125-129. doi:10.1152/nips.01427.2002.
[4]	KIMMEL E C, STILL K R. Acute lung injury,acute respiratory distress syndrome and inhalation injury:an overview[J]. Drug Chem Toxicol, 1999, 22(1):91-128. doi:10.3109/01480549909029726.
[5]	GUO B, BAI Y, MA Y, et al. Preclinical and clinical studies of smoke-inhalation-induced acute lung injury:update on both pathogenesis and innovative therapy[J]. Ther Adv Respir Dis, 2019,13:1753466619847901. doi:10.1177/1753466619847901.
[6]	MILTON-JONES H, SOUSSI S, DAVIES R, et al. An international RAND/UCLA expert panel to determine the optimal diagnosis and management of burn inhalation injury[J]. Crit Care, 2023, 27(1):459. doi:10.1186/s13054-023-04718-w.
[7]	COLONNA M, BUTOVSKY O. Microglia function in the central nervous system during health and neurodegeneration[J]. Annu Rev Immunol, 2017,35:441-468. doi:10.1146/annurev-immunol-051116-052358.
[8]	YANG R Q, GUO P F, MA Z, et al. Effects of simvastatin on iNOS and caspase-3 levels and oxidative stress following smoke inhalation injury[J]. Mol Med Rep, 2020, 22(6):5479. doi:10.3892/mmr.2020.11413.
[9]	毛权西, 李作孝. 依达拉奉右莰醇通过铁死亡-脂质过氧化通路对脑出血大鼠神经保护的作用机制[J]. 天津医药, 2023, 51(11):1199-1205.
	MAO Q X, LI Z X. Neuroprotective mechanism of edaravone dexborneol in rats with cerebral hemorrhage through ferroptosis-lipid peroxidation pathway[J]. Tianjin Med J, 2023, 51(11):1199-1205. doi:10.11958/20221777.
[10]	FANG X, ARDEHALI H, MIN J, et al. The molecular and metabolic landscape of iron and ferroptosis in cardiovascular disease[J]. Nat Rev Cardiol, 2023, 20(1):7-23. doi:10.1038/s41569-022-00735-4.
[11]	LI J, LI M, GE Y, et al. β-amyloid protein induces mitophagy-dependent ferroptosis through the CD36/PINK/PARKIN pathway leading to blood-brain barrier destruction in Alzheimer's disease[J]. Cell Biosci, 2022, 12(1):69. doi:10.1186/s13578-022-00807-5.
[12]	RYAN S K, ZELIC M, HAN Y, et al. Microglia ferroptosis is regulated by SEC24B and contributes to neurodegeneration[J]. Nat Neurosci, 2023, 26(1):12-26. doi:10.1038/s41593-022-01221-3.
[13]	张赟, 李珂, 补王珍. 电针调控Nrf2/HO-1通路对缺血缺氧性脑损伤大鼠小胶质细胞活化的影响[J]. 天津医药, 2023, 51(2):149-154.
	ZHANG Y, LI K, BU W Z. Effect of electroacupuncture on the activation of microglia in rats with hypoxia-ischemia brain damage by regulating Nrf2/HO-1 pathway[J]. Tianjin Med J, 2023, 51(2):149-154. doi:10.11958/20220792.
[14]	XIAO P, SUN S, CAO J, et al. Expression profile of microRNAs in bronchoalveolar lavage fluid of rats as predictors for smoke inhalation injury[J]. Burns, 2018, 44(8):2042-2450. doi:10.1016/j.burns.2018.07.009.
[15]	GUPTA K, MEHROTRA M, KUMAR P, et al. Smoke inhalation injury:etiopathogenesis,diagnosis,and management[J]. Indian J Crit Care Med, 2018, 22(3):180-188. doi:10.4103/ijccm.IJCCM_460_17.
[16]	SOLEIMANI F, DOBARADARAN S, DE-LA-TORRE G E, et al. Content of toxic components of cigarette,cigarette smoke vs cigarette butts:a comprehensive systematic review[J]. Sci Total Environ, 2022, 813:152667. doi:10.1016/j.scitotenv.2021.152667.
[17]	GALARIS D, BARBOUTI A, PANTOPOULOS K. Iron homeostasis and oxidative stress:An intimate relationship[J]. Biochim Biophys Acta Mol Cell Res, 2019, 1866(12):118535. doi:10.1016/j.bbamcr.2019.118535.
[18]	HAN C, LIU Y, DAI R, et al. Ferroptosis and its potential role in human diseases[J]. Front Pharmacol, 2020, 11:239. doi:10.3389/fphar.2020.00239.
[19]	ZHANG C, LIU X, JIN S, et al. Ferroptosis in cancer therapy:a novel approach to reversing drug resistance[J]. Mol Cancer, 2022, 21(1):47. doi:10.1186/s12943-022-01530-y.
[20]	DU L, WU Y, FAN Z, et al. The role of ferroptosis in nervous system disorders[J]. J Integr Neurosci, 2023, 22(1):19. doi:10.31083/j.jin2201019.
[21]	LIU S, GAO X, ZHOU S. New target for prevention and treatment of neuroinflammation: microglia iron accumulation and ferroptosis[J]. ASN Neuro, 2022,14:17590914221133236. doi:10.1177/17590914221133236.
[22]	HU X, ZHANG H, ZHANG Q, et al. Emerging role of STING signalling in CNS injury:inflammation,autophagy,necroptosis,ferroptosis and pyroptosis[J]. J Neuroinflammation, 2022, 19(1):242. doi:10.1186/s12974-022-02602-y.
[23]	LI Q S, JIA Y J. Ferroptosis:a critical player and potential therapeutic target in traumatic brain injury and spinal cord injury[J]. Neural Regen Res, 2023, 18(3):506-512. doi:10.4103/1673-5374.350187.
[24]	WU Q, LIU C, LIU D, et al. Polystyrene nanoplastics-induced lung apoptosis and ferroptosis via ROS-dependent endoplasmic reticulum stress[J]. Sci Total Environ, 2024, 912:169260. doi:10.1016/j.scitotenv.2023.169260.
[25]	SCARPELLINI C, KLEJBOROWSKA G, LANTHIER C, et al. Beyond ferrostatin-1:a comprehensive review of ferroptosis inhibitors[J]. Trends Pharmacol Sci, 2023, 44(12):902-916. doi:10.1016/j.tips.2023.08.012.
[26]	LI C, WU Z, XUE H, et al. Ferroptosis contributes to hypoxic-ischemic brain injury in neonatal rats:role of the SIRT1/Nrf2/GPx4 signaling pathway[J]. CNS Neurosci Ther, 2022, 28(12):2268-2280. doi:10.1111/cns.13973.
[27]	ENTEZARI S, HAGHI S M, NOROUZKHANI N, et al. Iron chelators in treatment of iron overload[J]. J Toxicol, 2022,2022:4911205. doi:10.1155/2022/4911205.
[28]	CHENG H, WANG P, WANG N, et al. Neuroprotection of NRF2 against ferroptosis after traumatic brain injury in mice[J]. Antioxidants, 2023, 12(3):731. doi:10.3390/antiox12030731.
[29]	ADAMIEC-ORGANISCIOK M, WEGRZYN M, CIENCIALA L, et al. Compensative resistance to erastin-induced ferroptosis in GPX4 knock-out mutants in HCT116 cell lines[J]. Pharmaceuticals, 2023, 16(12):1710. doi:10.3390/ph16121710.

基因名称	引物序列（5'→3'）	产物大小/bp
IL-1β	上游：ATCCAGCACTCTGCTTTCAGG 下游：TGCATCTGTAGGAGTCCCTGT	180
IL-6	上游：CTCTGGGAAATCGTGGAAAT 下游CCAGTTTGGTAGCATCCATC	134
IL-8	上游：ACCCGCTCGCTTCTCTGT 下游：AAGGGAGCTTCAGGGTCAAG	233
TNF-α	上游：ATGAGAAGTTCCCAAATGGC 下游：CTCCACTTGGTGGTTTGCTA	125
Zo-1	上游TCTTGCAAAGTATCCCTTCTGT 下游CAGAAATCGTGCTGATGTGCC	102
VE-Cadherin	上游CACCACAGCTATCACGTTTTGC 下游：CCAAGTCTCCCCTGGTTAGG	132
Occludin	上游：CCGGCCGCCAAGGTTC 下游：ACATGCATCTCTCCGCCATAC	183
Claudin-5	上游：CACACCTCGTCGCTAGTGC 下游GCTCCCAAGATAAGCGAACCT	168
ACSL4	上游：TCAAGGGAGGCTTTAGGCGA 下游：GCCTCCGCTCACTAAGGAC	117
NCOA4	上游：GCCAGAGCAGAAGTCAGCAT 下游：GTCCTGTGGGTTGGTACTGG	118
GPX4	上游：GATGAGCTGGGGCCGTCTG 下游：TGACGATGCACACGAAACCC	200
SLC7A11	上游：AATACGGAGCCTTCCACGAG 下游：CTCCAGGGGCAGTCAGTTAG	86
GAPDH	上游：CCCCATACACAGTGTTAGCC 下游：GAGTGATTTTCCCGTCC	96

基因名称	引物序列（5'→3'）	产物大小/bp
IL-1β	上游：ATCCAGCACTCTGCTTTCAGG 下游：TGCATCTGTAGGAGTCCCTGT	180
IL-6	上游：CTCTGGGAAATCGTGGAAAT 下游CCAGTTTGGTAGCATCCATC	134
IL-8	上游：ACCCGCTCGCTTCTCTGT 下游：AAGGGAGCTTCAGGGTCAAG	233
TNF-α	上游：ATGAGAAGTTCCCAAATGGC 下游：CTCCACTTGGTGGTTTGCTA	125
Zo-1	上游TCTTGCAAAGTATCCCTTCTGT 下游CAGAAATCGTGCTGATGTGCC	102
VE-Cadherin	上游CACCACAGCTATCACGTTTTGC 下游：CCAAGTCTCCCCTGGTTAGG	132
Occludin	上游：CCGGCCGCCAAGGTTC 下游：ACATGCATCTCTCCGCCATAC	183
Claudin-5	上游：CACACCTCGTCGCTAGTGC 下游GCTCCCAAGATAAGCGAACCT	168
ACSL4	上游：TCAAGGGAGGCTTTAGGCGA 下游：GCCTCCGCTCACTAAGGAC	117
NCOA4	上游：GCCAGAGCAGAAGTCAGCAT 下游：GTCCTGTGGGTTGGTACTGG	118
GPX4	上游：GATGAGCTGGGGCCGTCTG 下游：TGACGATGCACACGAAACCC	200
SLC7A11	上游：AATACGGAGCCTTCCACGAG 下游：CTCCAGGGGCAGTCAGTTAG	86
GAPDH	上游：CCCCATACACAGTGTTAGCC 下游：GAGTGATTTTCCCGTCC	96

组别	IL-1β	IL-6	IL-8	TNF-α
Control组	1.00±0.18	1.00±0.19	1.00±0.17	1.00±0.21
SII组	2.74±0.42^a	2.61±0.49^a	3.64±0.67^a	5.00±1.11^a
Fer-1组	1.57±0.25^b	1.34±0.20^b	1.57±0.36^b	2.77±0.47^b
DFO组	1.46±0.27^b	1.53±0.29^b	1.69±0.37^b	2.73±0.75^b
F	31.563^＊＊	24.594^＊＊	35.215^＊＊	26.198^＊＊

组别	IL-1β	IL-6	IL-8	TNF-α
Control组	1.00±0.18	1.00±0.19	1.00±0.17	1.00±0.21
SII组	2.74±0.42^a	2.61±0.49^a	3.64±0.67^a	5.00±1.11^a
Fer-1组	1.57±0.25^b	1.34±0.20^b	1.57±0.36^b	2.77±0.47^b
DFO组	1.46±0.27^b	1.53±0.29^b	1.69±0.37^b	2.73±0.75^b
F	31.563^＊＊	24.594^＊＊	35.215^＊＊	26.198^＊＊

组别	Claudin-5	Occludin	VE-Cadherin	Zo-1
Control组	1.00±0.13	1.00±0.19	1.00±0.13	1.00±0.14
SII组	2.88±0.30^a	3.06±0.38^a	3.47±0.71^a	3.11±0.53^a
Fer-1组	1.36±0.20^b	1.79±0.28^b	1.79±0.38^b	1.60±0.44^b
DFO组	1.54±0.31^b	1.69±0.22^b	1.90±0.21^b	1.72±0.27^b
F	53.833^＊＊	47.648^＊＊	30.353^＊＊	28.411^＊＊

小胶质细胞铁死亡在烟雾吸入性脑损伤中的作用机制探讨

Mechanism of microglia ferroptosis in smoke inhalation-induced brain injury

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组别	ACSL4	NCOA4	GPX4	SLC7A11
Control组	1.00±0.12	1.00±0.20	1.00±0.15	1.00±0.19
SII组	4.16±0.73^a	2.79±0.43^a	0.46±0.06^a	0.46±0.07^a
Fer-1组	1.98±0.31^b	1.42±0.31^b	0.65±0.11^b	0.65±0.07^b
DFO组	2.10±0.46^b	1.53±0.31^b	0.64±0.08^b	0.65±0.09^b
F	40.712^＊＊	28.591^＊＊	22.749^＊＊	18.477^＊＊

组别	铁含量/ （μmol/L）	LPO/ （μmol/g）	MDA/ （μmol/L）	SOD/ （μmol/L）	GSH/ （μmol/g）
Control组	1.88±0.21	18.81±0.08	5.01±0.62	0.22±0.07	0.82±0.06
SII组	5.25±0.59^a	43.35±8.90^a	11.14±1.07^a	0.10±0.02^a	0.46±0.05^a
Fer-1组	2.18±0.31^b	27.34±3.94^b	7.51±0.77^b	0.20±0.02^b	0.67±0.05^b
DFO组	2.24±0.40^b	21.16±4.65^b	7.07±1.26^b	0.20±0.01^b	0.70±0.05^b
F	78.792^＊＊	18.703^＊＊	35.263^＊＊	72.402^＊＊	40.204^＊＊

组别	存活率	凋亡率
Control组	100.00±4.87	5.12±1.40
Erastin组	69.39±6.70^a	24.36±2.74^a
Fer-1组	88.81±4.07^b	13.95±2.54^b
DFO组	90.08±4.81^b	15.61±2.02^b
F	23.342^＊＊	49.711^＊＊

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