CX3CR1调节小胶质细胞极化加重脑缺血/再灌注损伤

doi:10.16352/j.issn.1001-6325.2026.10.1336

基础医学与临床 ›› 2026, Vol. 46 ›› Issue (10): 1336-1343.doi: 10.16352/j.issn.1001-6325.2026.10.1336

CX3CR1调节小胶质细胞极化加重脑缺血/再灌注损伤

孟庆花¹, 田伟², 李琳¹, 张维智^1*, 彭双春³

1.山西省儿童医院/山西省妇幼保健院麻醉科,山西太原 030025;
2.山西省人民医院麻醉科,山西太原 030012;
3.乐山市中医医院麻醉科,四川乐山 614000

收稿日期:2025-08-18 修回日期:2025-12-03 出版日期:2026-10-05 发布日期:2026-09-18
通讯作者: ^*Mengqinhua1984@aliyun.com
基金资助:
山西省基础研究计划(202203021221290)

CX3CR1 aggravates cerebral ischemia/ reperfusion injury by regulating microglial polarization

MENG Qinghua¹, TIAN Wei², LI Lin¹, ZHANG Weizhi^1*, PENG Shuangchun³

1. Department of Anesthesiology, Shanxi Maternal and Child Health Hospital, Taiyuan 030025;
2. Department of Anesthesiology, Shanxi People′s Hospital, Taiyuan 030012;
3. Department of Anesthesiology, Leshan Hospital of Traditional Chinese Medicine, Leshan 614000, China

Received:2025-08-18 Revised:2025-12-03 Online:2026-10-05 Published:2026-09-18
Contact: ^*Mengqinhua1984@aliyun.com

摘要/Abstract

摘要： 目的探究CX3C趋化因子受体1(CX3CR1)通过乳脂球表皮生长因子8(MFGE8)/Janus激酶2(JAK2)/信号转导与转录激活因子3(STAT3)信号通路调节小胶质细胞极化,在脑缺血/再灌注损伤(CI/RI)中的作用及机制。方法采用短暂性大脑中动脉闭塞/再灌注(tMCAO)模型,将小鼠分为假手术组、tMCAO组、shNC组、shCX3CR1组及shCX3CR1+shMFGE8组。通过TTC染色评估脑梗死体积;Longa评分评估神经功能缺损;HE染色和尼氏染色观察脑组织病理变化;Western blot和RT-qPCR检测脑组织中MFGE8/JAK2/STAT3通路相关蛋白及小胶质细胞极化标志物基因的表达;ELISA法检测炎性因子(TNF-α、IL-6、IL-1β等)含量。结果与假手术组相比,tMCAO组脑梗死体积和神经功能评分显著升高,神经元坏死增多,核固缩及结构破坏明显,促炎细胞因子含量增加;脑组织中 Cx3cr1 mRNA和CX3CR1蛋白水平升高,Mfge8 mRNA和MFGE8蛋白水平降低(P＜0.05)。与shNC组相比,shCX3CR1组脑梗死体积和神经功能评分降低,神经元坏死减少,促炎细胞因子水平下降;小胶质细胞M2型标志物基因(Arg1、CD206、YM1/2)表达升高,M1型标志物基因(Nos2、TNF和Il1b)表达降低;MFGE8蛋白水平升高,而JAK2和STAT3总蛋白水平不变,p-JAK2和p-STAT3磷酸化水平降低(P＜0.05)。与shCX3CR1组相比,shCX3CR1+shMFGE8组上述指标呈相反趋势(P＜0.05)。结论 CX3CR1可能通过抑制MFGE8激活JAK2/STAT3信号通路,促进小胶质细胞向M1型极化,加重神经元坏死和CI/RI。

关键词: 脑缺血/再灌注, 小胶质细胞极化, CX3C趋化因子受体1, 乳脂球-表皮生长因子8/Janus激活激酶2信号转导与转录激活因子3信号通路

Abstract: Objective To investigate the role and mechanism of CX3C chemokine receptor 1 (CX3CR1) in regulating microglial polarization via the MFGE8/Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway in cerebral ischemia/reperfusion injury (CI/RI). Methods A transient middle cerebral artery occlusion (tMCAO) model was established in mice, which were randomly divided into the following groups: sham operation, tMCAO, shNC, shCX3CR1, and shCX3CR1+shMFGE8. Infarct volume was assessed by TTC staining; neurological deficits were evaluated using the Longa scoring system; and histopathological changes in brain tissue were observed via HE staining and Nissl staining. Western blot and RT-qPCR were used to detect the expression of proteins related to the MFGE8/JAK2/STAT3 pathway and marker genes of microglial polarization. The levels of inflammatory cytokines (TNF-α, IL-6, IL-1β, etc.) in brain tissue were measured by ELISA. Results Compared with the sham group, the tMCAO group showed significantly increased infarct volume and neurological scores, accompanied by increased neuronal necrosis, nuclear pyknosis, and structural disruption, as well as elevated pro-inflammatory cytokine levels. The mRNA and protein levels of Cx3cr1 were up-regulated, while those of Mfge8 were down-regulated (P＜0.05). Compared with the shNC group, the shCX3CR1 group exhibited reduced infarct volume and neurological scores, decreased neuronal necrosis, and lower pro-inflammatory cytokine levels. Additionally, the expression of M2-type microglial marker genes (Arg1, Cd206, YM1/2) was increased, whereas M1-type marker genes (Nos2, Tnf, Il1b) were decreased. MFGE8 protein levels were elevated, while total JAK2 and STAT3 protein levels remained unchanged, with reduced phosphorylation levels of p-JAK2 and p-STAT3 (P＜0.05). Compared with the shCX3CR1 group, the shCX3CR1+shMFGE8 group showed opposite trends in the above indicators (P＜0.05). Conclusions CX3CR1 may aggravate neuronal necrosis and CI/RI by inhibiting MFGE8 to activate the JAK2/STAT3 signaling pathway, thereby promoting M1-type microglial polarization.

Key words: cerebral ischemia/reperfusion, microglia polarization, CX3C chemokine receptor 1, milk fat globule-EGF factor 8/janus activated kinase / signal transducer and activator of transcription 3 signaling pathway

中图分类号:

孟庆花, 田伟, 李琳, 张维智, 彭双春. CX3CR1调节小胶质细胞极化加重脑缺血/再灌注损伤[J]. 基础医学与临床, 2026, 46(10): 1336-1343.

MENG Qinghua, TIAN Wei, LI Lin, ZHANG Weizhi, PENG Shuangchun. CX3CR1 aggravates cerebral ischemia/ reperfusion injury by regulating microglial polarization[J]. Basic & Clinical Medicine, 2026, 46(10): 1336-1343.

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CX3CR1调节小胶质细胞极化加重脑缺血/再灌注损伤

CX3CR1 aggravates cerebral ischemia/ reperfusion injury by regulating microglial polarization

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