巨噬细胞移动抑制因子在大鼠蛛网膜下腔出血后早期脑损伤中的作用

doi:10.20047/j.issn1673-7210.2023.21.03

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摘要目的揭示巨噬细胞移动抑制因子（MIF）在大鼠蛛网膜下腔出血（SAH）后早期脑损伤（EBI）中的作用。方法将120只12月龄的健康雄性Sprague Dawley大鼠（清洁级）按照随机数字表法分为假手术（Sham）组、SAH组和抑制剂组，每组40只。手术操作前0.5 h，抑制剂组大鼠腹腔注射MIF抑制剂（10 mg/kg），SAH组大鼠和Sham组大鼠腹腔注射同等剂量0.9%氯化钠注射液，随后采用枕大池二次注血法制作SAH组和抑制剂组大鼠SAH模型，Sham组大鼠模型两次注入的等量液体则为0.9%氯化钠注射液。术后行脑皮层MIF蛋白、白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）、IL-6、神经细胞凋亡、脑含水量、血脑屏障通透性和神经行为学功能测定。结果与Sham组比较，SAH组大鼠MIF蛋白、IL-1β、TNF-α、IL-6、凋亡神经细胞比例、脑含水量指数和伊文氏蓝含量显著升高，神经行为学评分显著下降（P＜0.05）；与SAH组比较，抑制剂组大鼠IL-1β、TNF-α、IL-6、凋亡神经细胞比例、脑含水量指数和伊文氏蓝含量显著下降，神经行为学评分显著升高（P＜0.05），而SAH组和抑制剂组大鼠MIF蛋白水平比较，差异无统计学意义（P＞0.05）。结论 MIF可能诱发大鼠SAH后EBI，而抑制MIF作用可能对EBI起到保护作用。

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	申屠华松　　陈亦华　　程振宇

关键词 ：巨噬细胞移动抑制因子, 大鼠, 蛛网膜下腔出血, 早期脑损伤, 机制

Abstract：Objective To investigate the role of macrophage migration inhibitory factor (MIF) in early brain injury (EBI) after subarachnoid hemorrhage (SAH) in rats. Methods A total of 120 12-month-old healthy male Sprague Dawley rats (clean grade) were divided into Sham group, SAH group and inhibitor group according to random number table method, with 40 rats in each group. 0.5 h before operation, rats in the inhibitor group were intraperitoneally injected with MIF inhibitor (10 mg/kg), and rats in the SAH group and Sham group were intraperitoneally injected with 0.9% sodium chloride injection, and then SAH group and inhibitor group were constructed by secondary blood injection in the occipital cisterna. In the Sham group, 0.9% sodium chloride injection was injected with the same amount of liquid twice. Cortical MIF protein, interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), IL-6, nerve cell apoptosis, brain water content, blood-brain barrier permeability and neurobehavioral function were determined after surgery. Results Compared with Sham group, MIF protein, IL-1β, TNF-α, IL-6, proportion of apoptotic nerve cells, brain water content index and content of Evan’s blue of rats in SAH group were significantly increased, and neurobehavioral scores were significantly decreased (P＜0.05). Compared with SAH group, IL-1β, TNF-α, IL-6, proportion of apoptotic nerve cells, brain water content index and content of Evan’s blue in inhibitor group were significantly decreased, and neurobehavioral scores were significantly increased (P＜0.05), but there was no statistical significance in MIF protein level between SAH group and inhibitor group (P＞0.05). Conclusion MIF may induce EBI after SAH, and inhibition of MIF may protect EBI.

Key words： Macrophage migration inhibitory factor Rats Subarachnoid hemorrhage Early brain injury Mechanisms

基金资助:浙江省金华市科技计划项目（2021-4-063）；
浙江省医药卫生科技计划项目（2020KY1017）。

作者简介: 申屠华松（1977.11-），男，副主任医师，主要从事蛛网膜下腔出血的基础和临床研究。

引用本文:

申屠华松　　陈亦华　　程振宇. 巨噬细胞移动抑制因子在大鼠蛛网膜下腔出血后早期脑损伤中的作用[J]. 中国医药导报, 2023, 20(21): 14-18.
SHENTU Huasong CHEN Yihua CHENG Zhenyu. Role of macrophage migration inhibitor in early brain injury after subarachnoid hemorrhage in rats. 中国医药导报, 2023, 20(21): 14-18.

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[1] Geraghty JR，Davis JL，Testai FD. Neuroinflammation and microvascular dysfunction after experimental subarachnoid hemorrhage：emerging components of early brain injury related to outcome [J]. Neurocrit Care，2019，31（2）：373-389.
[2] De Nardo TFS，Bertolo PHL，Bernardes PA，et al. Contribution of astrocytes and macrophage migration inhibitory factor to immune-mediated canine encephalitis caused by the distemper virus [J]. Vet Immunol Immunopathol，2020，221：110010.
[3] Zhu Z，Hu Y，Zhou Y，et al. Macrophage migration inhibitory factor promotes chemotaxis of astrocytes through regulation of cholesterol 25-Hydroxylase following rat spinal cord injury [J]. Neuroscience，2019，408：349-360.
[4] Ji H，Zhang Y，Chen C，et al. D-dopachrome tautomerase ac- tivates COX2/PGE2 pathway of astrocytes to mediate inflammation following spinal cord injury [J]. J Neuroinflammation，2021，18（1）：130.
[5] Zhang Y，Zhou Y，Chen S，et al. Macrophage migration inhibitory factor facilitates prostaglandin E2 production of astrocytes to tune inflammatory milieu following spinal cord injury [J]. J Neuroinflammation，2019，16（1）：85.
[6] Cheng B，Wang Q，Song Y，et al. MIF inhibitor，ISO-1，attenuates human pancreatic cancer cell proliferation，migration and invasion in vivo，and suppresses xenograft tumour growth in vivo [J]. Sci Rep，2020，10（1）：6741.
[7] Liu YC，Tsai YH，Tang SC，et al. Cytokine MIF enhances blood-brain barrier permeability：impact for therapy in ischemic stroke [J]. Sci Rep，2018，8（1）：743.
[8] Zhao Y，Wei X，Li W，et al. Inhibition of macrophage migration inhibitory factor protects against inflammation through a Toll-like receptor-related pathway after diffuse axonal injury in rats [J]. Biomed Res Int，2020，2020：5946205.
[9] Newell-Rogers MK，Rogers SK，Tobin RP，et al. Antagonism of macrophage migration inhibitory factory （MIF） after traumatic brain injury ameliorates astrocytosis and peripheral lymphocyte activation and expansion [J]. Int J Mol Sci，2020， 21（20）：7448.
[10] Bae SH，Yoo MR，Kim YY，et al. Brain-derived neurotrophic factor mediates macrophage migration inhibitory factor to protect neurons against oxygen-glucose deprivation [J]. Neural Regen Res，2020，15（8）：1483-1489.
[11] Roux S，Loffler BM，Gray GA，et al. The role of endothelin in experimental cerebral vasospasm [J]. Neurosurgery，1995， 37（1）：78-85.
[12] Liu L，Kawakita F，Fujimoto M，et al. Role of Periostin in Early Brain Injury After Subarachnoid Hemorrhage in Mice [J]. Stroke，2017，48（4）：1108-1111.
[13] 赵龙，唐晓平，段劼，等.枕大池二次注血建立SAH大鼠模型失败原因分析[J].中华神经外科疾病研究杂志，2012，11（5）：389-391.
[14] Kaoutzanis M，Yokota M，Sibilia R，et al. Neurologic evaluation in a canine model of single and double subarachnoid hemorrhage[J]. J Neurosci Methods，1993，50（3）：301-307.
[15] Wen Y，Cai W，Yang J，et al. Targeting Macrophage Migration Inhibitory Factor in Acute Pancreatitis and Pancreatic Cancer [J]. Front Pharmacol，2021，12：638950.
[16] Chen Y，Wang CY，Zhao L，et al. Inhibition of macrophage migration inhibitory factor prevents thyroid dysfunction in pregnant rats with acute pancreatitis [J]. Int Immunopharmacol，2020，87：106771.
[17] Luo Y，Yi H，Huang X，et al. Inhibition of macrophage migration inhibitory factor （MIF） as a therapeutic target in bleo- mycin-induced pulmonary fibrosis rats [J]. Am J Physiol Lung Cell Mol Physiol，2021，321（1）：L6-L16.
[18] Tilstam PV，Schulte W，Holowka T，et al. MIF but not MIF-2 recruits inflammatory macrophages in an experimental polymicrobial sepsis model [J]. J Clin Invest，2021， 131（23）：e127171.
[19] Bozza MT，Lintomen L，Kitoko JZ，et al. The Role of MIF on Eosinophil Biology and Eosinophilic Inflammation [J]. Clin Rev Allergy Immunol，2020，58（1）：15-24.
[20] Charan M，Das S，Mishra S，et al. Macrophage migration inh- ibitory factor inhibition as a novel therapeutic approach against triple-negative breast cancer [J]. Cell Death Dis，2020， 11（9）：774.
[21] Bilsborrow JB，Doherty E，Tilstam PV，et al. Macrophage mig- ration inhibitory factor （MIF） as a therapeutic target for rhe- umatoid arthritis and systemic lupus erythematosus [J]. Expert Opin Ther Targets，2019，23（9）：733-744.
[22] Sinitski D，Kontos C，Krammer C，et al. Macrophage migration inhibitory factor （MIF）-based therapeutic concepts in atherosclerosis and inflammation [J]. Thromb Haemost，2019， 119（4）：553-566.
[23] Noe JT，Mitchell RA. MIF-Dependent Control of Tumor Immunity [J]. Front Immunol，2020，11：609948.
[24] Wang CW，Ma PJ，Wang YY，et al. Serum level of macrophage migration inhibitory factor predicts severity and prognosis in patients with ischemic stroke [J]. Cytokine，2019，115：8-12.
[25] Zis O，Zhang S，Dorovini-Zis K，et al. Hypoxia signaling regulates macrophage migration inhibitory factor （MIF） expression in stroke [J]. Mol Neurobiol，2015，51（1）：155-167.