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井冈山大学基础医学院,江西 吉安 343009
肖智勇,第一作者,副主任医师,研究方向:神经损伤与修复,E-mail: hanbaobaoinlove@163.com
收稿日期:2024-07-27,
录用日期:2025-04-06,
纸质出版日期:2025-05-20
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肖智勇,魏楚蓉.全氟辛烷磺酸诱导血脑屏障损伤的信号通路研究进展[J].中山大学学报(医学科学版),2025,46(03):384-390.
XIAO Zhiyong,WEI Churong.Research Progress on the Signaling Pathway of the Blood-Brain Barrier Injuries Induced by PFOS[J].Journal of Sun Yat-sen University(Medical Sciences),2025,46(03):384-390.
肖智勇,魏楚蓉.全氟辛烷磺酸诱导血脑屏障损伤的信号通路研究进展[J].中山大学学报(医学科学版),2025,46(03):384-390. DOI: 10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2025.0303.
XIAO Zhiyong,WEI Churong.Research Progress on the Signaling Pathway of the Blood-Brain Barrier Injuries Induced by PFOS[J].Journal of Sun Yat-sen University(Medical Sciences),2025,46(03):384-390. DOI: 10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2025.0303.
全氟辛烷磺酸(PFOS)具有显著生物毒性,能够破坏血脑屏障的结构和功能。PFOS暴露可使血脑屏障紧密连接蛋白降解和星形胶质细胞损伤,进而导致血脑屏障通透性增加;以及多条信号通路的激活,包括PI3K/AKT、p38 MAPK、氧化应激和钙信号通路。血脑屏障的损伤可能引发多种神经系统疾病,而PFOS通过多种机制影响血脑屏障的功能,进而干扰中枢神经系统的正常运转。本文旨在综述PFOS诱导血脑屏障损伤相关信号通路的研究进展,并建议未来研究可聚焦于发展更精确的体内模型、利用更先进的分子生物学技术揭示更细致的分子机制、探讨PFOS与其他环境毒素的协同作用,以期为临床防治PFOS诱导的神经系统疾病提供科学依据。
Perfluorooctane sulfonate (PFOS) has significant biotoxicity and can disrupt the structure and function of the blood-brain barrier. PFOS exposure can lead to the degradation of tight junction proteins in the blood-brain barrier and damage to astrocytes, resulting in increased permeability of the blood-brain barrier, as well as the activation of multiple signaling pathways, including PI3K/AKT, p38 MAPK, oxidative stress, and calcium signaling pathways. Damage to the blood-brain barrier may trigger various neurological diseases, and PFOS affects the function of the blood-brain barrier through multiple mechanisms, thereby interfering with the normal operation of the central nervous system. This article aims to review the research progress on the signaling pathways related to PFOS-induced blood-brain barrier damage and suggests that future studies could focus on developing more precise
in vivo
models, utilizing advanced molecular biology techniques to reveal more detailed molecular mechanisms, and exploring the synergistic effects of PFOS with other environmental toxins, in order to provide scientific evidence for the clini
cal prevention and treatment of PFOS-induced neurological diseases.
Wang QY , Huang J , Liu Sh , et al . Aberrant hepatic lipid metabolism associated with gut microbiota dysbiosis triggers hepatotoxicity of novel PFOS alternatives in adult zebrafish [J]. Environ Int , 2022 , 166 : 107351 .
Xu DM , Li L , Tang LL , et al . Perfluorooctane sulfonate induces heart toxicity involving cardiac apoptosis and inflammation in rats [J]. Exp Ther Med , 2022 , 23 ( 1 ) : 14 .
Torres L , Redko A , Limper C , et al . Effect of perfluorooctanesulfonic acid (PFOS) on immune cell development and function in mice [J]. Immunol Lett , 2021 , 233 : 31 – 41 .
Alamo A , Vignera SL , Mogioì LM . In-vitro effects of perfluorooctanoic acid on human sperm function: what are the clinical consequences? [J]. J Clin Med , 2024 , 13 ( 8 ) : 2201 .
Foguth RM , Flynn RW , Perre CD , et al . Developmental exposure to perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) selectively decreases brain dopamine levels in northern leopard frogs [J]. Toxicol Appl Pharmacol , 2019 , 15 : 377 .
Gaballah S , Swank A , Sobus JR , et al . Evaluation of developmental toxicity, developmental neurotoxicity, and tissue dose in zebrafish exposed to GenX and other PFAS [J]. Environ Health Perspect , 2020 , 128 ( 4 ) : 47005 .
Cipollini V , Troili F , Giubilei F . Emerging biomarkers in vascular cognitive impairment and dementia: from pathophysiological pathways to clinical application [J]. Int J Mol Sci , 2019 , 20 ( 11 ) : 281 .
Daneman R , Prat A . The blood-brain barrier [J]. Csh Perspect Biol , 2015 , 7 ( 1 ) : a20412 .
Andjelkovic AV , Situ M , Citalan-Madrid AF , et al . Blood-brain barrier dysfunction in normal aging and neurodegeneration: mechanisms, impact, and treatments [J]. Stroke , 2023 , 54 ( 3 ) : 661 - 672 .
Haruwaka K , Ikegami A , Tachibana Y , et al . Dual microglia effects on blood-brain barrier permeability induced by systemic inflammation [J]. Nat Commun , 2019 , 10 ( 1 ) : 5816 .
Ronaldson PT , Davis TP . Regulation of blood-brain barrier integrity by microglia in health and disease: a therapeutic opportunity [J]. J Cereb Blood Flow Metab , 2020 , 40 ( 1 ) : S6 - S24 .
Chai AB , Callaghan R , Gelissen IC . Regulation of p-glycoprotein in the brain [J]. Int J Mol Sci , 2022 , 23 ( 23 ) : 14667 .
Cai ZY , Qiao PF , Wan CQ , et al . Role of blood-brain barrier in Alzheimer's disease [J]. J Alzheimers Dis , 2018 , 63 ( 4 ) : 1223 - 1234 .
Rempe RG , Hartz AMS , Soldner ELB , et al . Matrix metalloproteinase-mediated blood-brain barrier dysfunction in epilepsy [J]. J Neurosci , 2018 , 38 ( 18 ) : 4301 - 4315 .
Kim H , Shin JY , Lee YS , et al . Brain endothelial p-glycoprotein level is reduced in Parkinson's disease via a vitamin D receptor-dependent pathway [J]. Int J Mol Sci , 2020 , 21 ( 22 ) : 8538 .
陈家苗 , 王建设 . 新型全氟和多氟烷醚类化合物的环境分布与毒性研究进展 [J]. 生态毒理学报 , 2020 , 15 ( 5 ) : 28 - 34 .
Chen JM , Wang JS . Research progress in environmental distribution and toxicity of per- and polyfluoroalkyl ether substances [J]. Asi J Ecot , 2020 , 15 ( 5 ) : 28 - 34 .
Lochhead JJ , Yang J , Ronaldson PT , et al . Structure, function, and regulation of the blood-brain barrier tight junction in central nervous system disorders [J]. Front Physiol , 2020 , 11 : 914 .
Wang X , Li B , Zhao W , et al . Perfluorooctane sulfonate triggers tight junction “opening” in brain endothelial cells via phosphatidylinositol 3-kinase [J]. Biochem Bioph Res Co , 2011 , 410 ( 2 ) : 258 - 263 .
Wang J , Pan Y , Cui Q , et al . Penetration of PFASs across the blood cerebrospinal fluid barrier and its determinants in humans [J]. Environ Sci Technol , 2018 , 52 ( 22 ) : 13553 - 13561 .
Yu Y , Wang C , Zhang X , et al . Perfluorooctane sulfonate disrupts the blood-brain barrier through the crosstalk between endothelial cells and astrocytes in mice [J]. Environ Pollut , 2020 , 256 : 113429 .
杨茗惠 , 刘辉 , 佟湃舸 , 等 . 星形胶质细胞在血脑屏障发育与稳态维持中的作用机制 [J]. 生命科学 , 2023 , 35 ( 12 ) : 1569 - 1577 .
Yang MH , Liu H , Tong PG , et al . The role of astrocyte in development and maintenance of the blood brain barrier [J]. Chin Bull Lif Sci , 2023 , 35 ( 12 ) : 1569 - 1577 .
Chen X , Nie X , Mao J , et al . Perfluorooctane sulfonate mediates secretion of IL-1β through PI3K/AKT-NF-κB pathway in astrocytes [J]. Neurotoxicol Teratol , 2018 , 67 : 65 - 75 .
Dong L , Yang X , Gu W , et al . Connexin 43 mediates PFOS-induced apoptosis in astrocytes [J]. Chemosphere , 2015 , 132 : 8 - 16 .
Wang Y , Wang L , Hu T , et al . Hydrogen improves cell viability partly through inhibition of autophagy and activation of PI3K/Akt/GSK3β signal pathway in a microvascular endothelial cell model of traumatic brain injury [J]. Neurol Res , 2020 , 42 ( 6 ) : 487 - 496 .
Sweatt JD . The neuronal MAP kinase cascade: a biochemical signal integration system subserving synaptic plasticity and memory [J]. J Neurochem , 2001 , 76 ( 1 ) : 1 - 10 .
张震 , 王梅芳 , 宋远见 . 瞬态受体电位香草酸1通过抑制p-JNK和p-p38MAPK信号通路减轻小鼠脑缺血后血脑屏障损伤及焦虑样行为的机制 [J]. 实用医学杂志 , 2021 , 37 ( 17 ): 2182 - 2186 .
Zhang Z , Wang MF , Song YJ . Mechanism of TRPV1 attenuating blood-brain barrier damage and anxiety-like behaviors after cerebral ischemia in mice by inhibiting p-JNK and p-p38 MAPK signaling pathways [J]. J Pract Med , 2021 , 37 ( 17 ): 2182 - 2186 .
Nito C , Kamada H , Endo H , et al . Role of the p38 mitogen-activated protein kinase/cytosolic phospholipase A2 signaling pathway in blood-brain barrier disruption after focal cerebral ischemia and reperfusion [J]. J Cereb Blood Flow Metab , 2008 , 28 ( 10 ) : 1686 - 1696 .
Nito C , Kamada H , Endo H , et al . Involvement of mitogen-activated protein kinase pathways in expression of the water channel protein aquaporin-4 after ischemia in rat cortical astrocytes [J]. J Neurotrauma , 2012 , 29 ( 14 ) : 2404 - 2412 .
Shirley R , Ord E , Work L . Oxidative stress and the use of antioxidants in stroke [J]. Antioxidants , 2014 , 3 ( 3 ) : 472 - 501 .
Zheng DD , Liu J , Piao HL . ROS-triggered endothelial cell death mechanisms: focus on pyroptosis, parthanatos, and ferroptosis [J]. Front Immunol , 2022 , 13 : 1039241 .
Wang L , Mao B , Fan KY , et al . ROS attenuates TET2-dependent ZO-1 epigenetic expression in cerebral vascular endothelial cells [J]. Fluids Barriers CNS , 2022 , 19 ( 1 ) : 73 .
徐玮 , 梁文意 , 郭彩娟 , 等 . 白果内酯通过Nrf2/HO-1信号通路改善氧化应激所致体外血脑屏障损伤的研究 [J]. 广东药科大学学报 , 2019 , 35 ( 1 ) : 69 - 75 .
Xu W , Liang WY , Guo CJ , et al . Bilobalide attenuates in vitro blood-brain barrier damage caused by oxidative stress via Nrf2/HO-1 signaling pathway [J]. J Guangdong Pharm Univ , 2019 , 35 ( 1 ) : 69 - 75 .
Chen HS , Chen X , Li WT , et al . Targeting RNS/Caveolin-1/MMP signaling cascades to protect against cerebral ischemia-reperfusion injuries: potential application for drug discovery [J]. Acta Pharmacol Sin , 2018 , 39 ( 5 ) : 669 - 682 .
Omoike OE , Pack RP , Mamudu HM , et al . Association between per and polyfluoroalkyl substances and markers of inflammation and oxidative stress [J]. Environ Res , 2021 , 196 : 110361 .
Alharthy SA , Hardej D . The role of transcription factor Nrf2 in the toxicity of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) in C57BL/6 mouse astrocytes [J]. Environ Toxicol Pharmacol , 2021 , 86 : 103652 .
Qian Y , Ducatman A , Ward R , et al . Perfluorooctane sulfonate (PFOS) induces reactive oxygen species (ROS) production in human microvascular endothelial cells: role in endothelial permeability [J]. J Toxic Environ Health A , 2010 , 73 ( 12 ) : 819 - 836 .
Ge JB , Wang C , Nie XK , et al . ROS-mediated apoptosis of HAPI microglia through p53 signaling following PFOS exposure [J]. Environ Toxicol Pharmacol , 2016 , 46 : 9 - 16 .
Wang C , Nie XK , Zhang Y . Reactive oxygen species mediate nitric oxide production through ERK/JNK MAPK signaling in HAPI microglia after PFOS exposure [J]. Toxicol Appl Pharmacol , 2015 , 288 ( 2 ): 143 - 151 .
Ludtmann MHR , Abramov AY . Mitochondrial calcium imbalance in Parkinson's disease [J]. Neurosci Lett , 2018 , 663 : 86 - 90 .
Negri S , Sanford M , Shi H , et al . The role of endothelial TRP channels in age-related vascular cognitive impairment and dementia [J]. Front Aging Neurosci , 2023 , 15 : 1149820 .
Luo HL , Saubamea B , Chasseigneaux S , et al . Molecular and functional study of transient receptor potential vanilloid 1-4 at the rat and human blood-brain barrier reveals interspecies differences [J]. Front Cell Dev Biol , 2020 , 8 : 578514 .
Stoica R , Rusu CM , Staicu CE , et al . Ca²⁺ homeostasis in brain microvascular endothelial cells [J]. Int Rev Cell Mol Biol , 2021 , 362 : 55 - 110 .
Vazana U , Veksler R , Pell GS , et al . Glutamate-mediated blood-brain barrier opening: implications for neuroprotection and drug delivery [J]. J Neurosci , 2016 , 36 ( 29 ) : 7727 - 7739 .
Ding XW , Sun X , Shen XF , et al . Propofol attenuates TNF-α-induced MMP-9 expression in human cerebral microvascular endothelial cells by inhibiting Ca²⁺/CAMKⅡ/ERK/NF-κB signaling pathway [J]. Acta Pharmacol Sin , 2019 , 40 ( 10 ) : 1303 - 1313 .
Berntsen HF , Bjørklund CG , Strandabø R , et al . PFOS-induced excitotoxicity is dependent on Ca²⁺ influx via NMDA receptors in rat cerebellar granule neurons [J]. Toxicol Appl Pharmacol , 2018 , 357 : 19 - 32 .
Yang JW , Wang Y , Xia YY , et al . PFOS elicits cytotoxicity in neuron through astrocyte-derived CaMKII - DLG1 signaling in vitro rat hippocampal model [J]. Neurochem Res , 2024 , 49 ( 5 ): 1226 - 1238 .
Xie MY , Lin ZY , Sun XF , et al . Per- and polyfluoroalkyl substances (PFAS) exposure in plasma and their blood-brain barrier transmission efficiency-a pilot study [J]. Environ Int , 2024 , 187 : 108719 .
Hong XW , Tao L , Guo L , et al . PFASs in cerebrospinal fluids and blood-CSF barrier permeability in patients with cognitive impairment [J]. Environ Sci Technol , 2024 , 58 ( 11 ): 5129 - 5138 .
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