大气细颗粒物PM<sub>2.5</sub>对人微血管内皮细胞坏死性凋亡的影响<sup>*</sup>

doi:10.3969/j.issn.1671-7171.2021.04.003

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摘要 【目的】 观察大气细颗粒物PM_2.5对体外培养血管内皮细胞坏死性凋亡的影响。【方法】 以人微血管内皮细胞株(HMEC-1)为研究对象,应用系列浓度PM_2.5处理24 h后,CCK-8检测HMEC-1细胞活力,试剂盒法检测培养上清液乳酸脱氢酶(LDH)的活性,Western blot法检测坏死性凋亡相关蛋白RIPK3和MLKL的表达及磷酸化水平,Transwell法检测HMEC-1细胞通透性改变。采用坏死性凋亡抑制剂(Necrostatin-1)处理后,观察PM_2.5对HMEC-1坏死性凋亡、细胞损伤和通透性的影响。【结果】 PM_2.5可呈剂量依赖性抑制HMEC-1的增殖,并增加培养上清液中LDH活性、RIPK3和MLKL的蛋白表达以及其磷酸化水平。Transwell检测结果表明PM_2.5可增加单层血管内皮细胞通透性,而坏死性凋亡抑制剂Necrostatin-1预处理可显著性抑制PM_2.5应激下血管内皮细胞RIPK3和MLKL的蛋白表达及磷酸化水平,降低上清液LDH活性和单层血管内皮细胞通透性。【结论】 PM_2.5可诱导HMEC-1坏死性凋亡,损伤血管内皮完整性。

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关键词 ：颗粒物, 内皮,血管/细胞学, 内皮细胞/代谢, 体外培养技术, 细胞凋亡

Abstract：【Objective】 To investigate the effect of atmospheric fine particles (particulate matter) PM_2.5 on necroptosis of human vascular endothelial cells.【Methods】 After 24 hours of treatment with a series of concentrations of PM_2.5, CCK-8 was used to detect cell viability in HMEC-1 cells (human microvascular endothelial cell line); and the culture supernatant was used to detect the level of lactate dehydrogenase (LDH) produced by HMEC-1 cells. Western blot method was applied to detect the expression and phosphorylation level of necroptosis-related proteins RIPK3 and MLKL. The permeability changes of vascular endothelial cells were measured by trans-well method. After treatment with necrostatin-1, an inhibitor of necroptosis, the effects of PM_2.5 on necroptosis, cell damage and permeability of vascular endothelial cells were observed and evaulated. 【Results】 PM_2.5 inhibited the proliferation of human microvascular endothelial cells in a dose-dependent manner. It increased the LDH activity in the culture supernatant and upregulated protein expression and phosphorylation levels of RIPK3 and MLKL. The result of trans-well assay showed that PM_2.5 increased the permeability of monolayer vascular endothelial cells. The pretreatment of necrostatin-1, an inhibitor of necroptosis, significantly inhibited the protein expression and phosphorylation levels of RIPK3 and MLKL in vascular endothelial cells under PM_2.5 stimulation, and reduced the activity of LDH in the supernatant and the permeability of monolayer vascular endothelial cells.【Conclusion】 PM_2.5 induces necroptosis of vascular endothelial cells and impairs the integrity of vascular endothelium.

Key words： Particulate Matter Endothelium, Vascular/CY Endothelial Cells/ME In Vitro Techniques Apoptosis

收稿日期: 2021-03-18

中图分类号:

R135.98

基金资助:* 国家自然科学基金资助项目(编号:81760019)

通讯作者: ** E-mail: 731734181@qq.com

引用本文:

黄一丹, 马丽, 周祎琦, 董良, 黄春波. 大气细颗粒物PM_2.5对人微血管内皮细胞坏死性凋亡的影响^*[J]. 医学临床研究, 2021, 38(4): 488-492.
HUANG Yi-dan, MA Li, ZHOU Yi-qi, et al. Effects of Atmospheric Fine Particulate Matter PM_2.5 on Necroptosis of Human Microvascular Endothelial Cells. JOURNAL OF CLINICAL RESEARCH, 2021, 38(4): 488-492.

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http://journal07.magtech.org.cn/yxlcyj/CN/10.3969/j.issn.1671-7171.2021.04.003 或 http://journal07.magtech.org.cn/yxlcyj/CN/Y2021/V38/I4/488

[1] GUO H, LI W, YAO F, et al. Who are more exposed to PM_2.5 pollution: A mobile phone data approach[J].Environ Int,2020, 143: 105821.
[2] HENDRYX M, LUO J, CHOJENTA C, et al. Air pollution exposures from multiple point sources and risk of incident chronic obstructive pulmonary disease (COPD) and asthma [J].Environ Res,2019, 179(Pt A): 108783.
[3] TANG W, HUANG S, DU L, et al. Expression of HMGB1 in maternal exposure to fine particulate air pollution induces lung injury in rat offspring assessed with micro-CT [J].Chem Biol Interact,2018, 280: 64-69.
[4] CHEN J J, MA W M, YUAN J L, et al. PM_2.5 exposure aggravates left heart failure induced pulmonary hypertension [J].Acta Cardiol,2019, 74(3): 238-244.
[5] WANG Y, TANG M. PM_2.5 induces autophagy and apoptosis through endoplasmic reticulum stress in human endothelial cells [J].Sci Total Environ,2020, 710: 136397.
[6] SU X, TIAN J, LI B, et al. Ambient PM_2.5 caused cardiac dysfunction through FoxO1-targeted cardiac hypertrophy and macrophage-activated fibrosis in mice [J].Chemosphere,2020, 247: 125881.
[7] CAO J, QIN G, SHI R, et al. Overproduction of reactive oxygen species and activation of MAPKs are involved in apoptosis induced by PM_2.5 in rat cardiac H9c2 cells [J].J Appl Toxicol,2016, 36(4): 609-617.
[8] ZHE-WEI S, LI-SHA G, YUE-CHUN L. The Role of Necroptosis in Cardiovascular Disease [J].Front Pharmacol,2018, 9: 721.
[9] CHO YS. The role of necroptosis in the treatment of diseases [J].BMB Rep,2018, 51(5): 219-224.
[10] LIU Y, LIU T, LEI T, et al. RIP1/RIP3-regulated necroptosis as a target for multifaceted disease therapy (Review) [J].Int J Mol Med,2019, 44(3): 771-786.
[11] MARTIN-SANCHEZ D, FONTECHA-BARRIUSO M, CARRASCO S, et al. TWEAK and RIPK1 mediate a second wave of cell death during AKI [J].Proc Natl Acad Sci U S A,2018, 115(16): 4182-4187.
[12] JIA Y, WANG F, GUO Q, et al. Curcumol induces RIPK1/RIPK3 complex-dependent necroptosis via JNK1/2-ROS signaling in hepatic stellate cells [J].Redox Biol,2018, 19: 375-387.
[13] WANG Y. PM_2.5 induces EMT and promotes CSC properties by activating Notch pathway in vivo and vitro [J].Ecotoxicol Environ Saf,2019, 178: 159-167.
[14] LIANG S, LV ZT, ZHANG J M, et al. Necrostatin-1 Attenuates Trauma-Induced Mouse Osteoarthritis and IL-1beta Induced Apoptosis via HMGB1/TLR4/SDF-1 in Primary Mouse Chondrocytes [J].Front Pharmacol,2018, 9: 1378.
[15] HU S, PARK J, LIU A, et al. Mesenchymal Stem Cell Microvesicles Restore Protein Permeability Across Primary Cultures of Injured Human Lung Microvascular Endothelial Cells [J].Stem Cells Transl Med,2018, 7(8): 615-624.
[16] JUN X, JIN G, FU C, et al. PM_2.5 promotes abdominal aortic aneurysm formation in angiotensin Ⅱ-infused apoe-/- mice [J].Biomed Pharmacother,2018, 104: 550-557.
[17] NOH J, SOHN J, HAN M, et al. Long-term Effects of Cumulative Average PM_2.5 Exposure on the Risk of Hemorrhagic Stroke [J].Epidemiology,2019, 30(Suppl 1): S90-S98.
[18] ZHOU Z, SHAO T, QIN M, et al. The effects of autophagy on vascular endothelial cells induced by airborne PM_2.5 [J].J Environ Sci (China),2018, 66: 182-187.
[19] YIN J, XIA W, LI Y, et al. COX-2 mediates PM_2.5-induced apoptosis and inflammation in vascular endothelial cells [J].Am J Transl Res,2017, 9(9): 3967-3976.
[20] WANG Y, TANG M. PM_2.5 induces ferroptosis in human endothelial cells through iron overload and redox imbalance [J].Environ Pollut,2019, 254(Pt A): 112937.
[21] YANG SH, LEE DK, SHIN J, et al. Nec-1 alleviates cognitive impairment with reduction of Abeta and tau abnormalities in APP/PS1 mice [J].EMBO Mol Med,2017, 9(1): 61-77.
[22] MIAO X, LI W, NIU B, et al. Mitochondrial dysfunction in endothelial cells induced by airborne fine particulate matter (<2.5 mum) [J].J Appl Toxicol,2019, 39(10): 1424-1432.
[23] RUI W, GUAN L, ZHANG F, et al. PM_2.5-induced oxidative stress increases adhesion molecules expression in human endothelial cells through the ERK/AKT/NF-kappaB-dependent pathway [J].J Appl Toxicol,2016, 36(1): 48-59.
[24] RHO S S, ANDO K, FUKUHARA S. Dynamic Regulation of Vascular Permeability by Vascular Endothelial Cadherin-Mediated Endothelial Cell-Cell Junctions [J].J Nippon Med Sch, 2017, 84(4): 148-159.
[25] DAI J, SUN C, YAO Z, et al. Exposure to concentrated ambient fine particulate matter disrupts vascular endothelial cell barrier function via the IL-6/HIF-1alpha signaling pathway [J].FEBS Open Bio,2016, 6(7): 720-728.