敲降MALAT1减轻ox-LDL诱导的巨噬细胞炎性反应和细胞损伤

doi:10.16352/j.issn.1001-6325.2026.03.0352

基础医学与临床 ›› 2026, Vol. 46 ›› Issue (3): 352-358.doi: 10.16352/j.issn.1001-6325.2026.03.0352

敲降MALAT1减轻ox-LDL诱导的巨噬细胞炎性反应和细胞损伤

宋宁¹, 罗俊一¹, 冀伟¹, 李艳红¹, 李晓梅^1*, 杨毅宁^2*

1.新疆医科大学第一附属医院心脏中心,新疆乌鲁木齐 830054;
2.新疆维吾尔自治区人民医院心内科,新疆乌鲁木齐 830001

收稿日期:2025-04-23 修回日期:2025-07-14 出版日期:2026-03-05 发布日期:2026-02-25
通讯作者: ^*yangyn5126@163.com; lixm505@163.com
基金资助:
新疆维吾尔自治区自然科学基金青年科学基金(2022D01C765);国家自然科学基金(8216020109,82460099)

Knock-down MALAT1 reduces ox-LDL- induced-inflammation and cell damage of macrophages

SONG Ning¹, LUO Junyi¹, JI Wei¹, LI Yanhong¹, LI Xiaomei^1*, YANG Yining^2*

1. Heart Center, the First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054;
2. Department of Cardiology, People′s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, China

Received:2025-04-23 Revised:2025-07-14 Online:2026-03-05 Published:2026-02-25
Contact: ^*yangyn5126@163.com; lixm505@163.com

摘要/Abstract

摘要： 目的探讨肺腺癌转移相关转录本1(MALAT1)在氧化型低密度脂蛋白(ox-LDL)诱导的巨噬细胞炎性反应和细胞损伤中的作用及潜在机制。方法使用佛波脂(PMA)诱导人单核细胞白血病细胞系(THP-1)分化为巨噬细胞,将巨噬细胞与ox-LDL共培养构建细胞损伤模型,并通过红油O染色观察脂质积累,转染shRNA敲降MALAT1的表达。实验组包括对照组、ox-LDL组、ox-LDL+shNC组和ox-LDL+shMALAT1组。细胞处理后,检测细胞内总胆固醇和三酰甘油的含量,流式细胞测量术检测凋亡,ELISA检测 IL-6、TNFα、MCP-1水平;RT-qPCR和Western blot检测NLRP3、RIPK1、caspase-8、p65和SR-A的表达。结果与对照组相比,ox-LDL组中细胞的脂质积累增加,总胆固醇和三酰甘油含量显著升高,细胞凋亡显著增加,IL-6、TNFα和MCP-1水平显著增加,且NLRP3、RIPK1、caspase-8、p-p65和SR-A的表达显著升高(P＜0.05)。与ox-LDL组相比,ox-LDL+shMALAT1组细胞中总胆固醇和三酰甘油含量显著下降,细胞凋亡显著降低, IL-6、TNFα和MCP-1显著减少,NLRP3、RIPK1、caspase-8、p-p65和SR-A的表达显著降低(P＜0.05)。结论 MALAT1在ox-LDL诱导的细胞损伤中可能通过调节NLRP3炎性小体及相关信号通路发挥重要作用。MALAT1的敲降可显著减轻ox-LDL诱导的炎性反应和细胞损伤,为动脉粥样硬化的治疗提供了新的潜在靶点。

关键词: 动脉粥样硬化, 肺腺癌转移相关转录本1(MALAT1), NOD样受体蛋白3(NLRP3), 炎性反应

Abstract: Objective To explore the role and potential mechanism of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in inflammatory response and cell damage of macrophages induced by oxidized low density lipoprotein (ox-LDL). Methods THP-1 cells were induced to differentiate into macrophages by phorbol ester(PMA). Macrophages were co-cultured with ox-LDL to construct a cell injury model. Lipid accumulation was observed by Oil Red O staining microscopy. MALAT1 was knocked down by transfection of shRNA. The experimental group included control group, ox-LDL group, ox-LDL+shNC group and ox-LDL+shMALAT1 group. Total cholesterol and triglyceride in cells were measured. Apoptosis was detected by flow cytometry. The level of IL-6, TNFα and MCP-1 were detected by ELISA. The expression of NLRP3, RIPK1, caspase-8, p65 and SR-A was detected by RT-qPCR and Western blot. Results Compared with the control group, the cell lipid accumulation, total cholesterol and triglyceride contents, cell apoptosis, IL-6, TNFα and MCP-1 levels and the expression of NLRP3, RIPK1, caspase-8, p-p65 and SR-A increased significantly in ox-LDL group(P＜0.05). Compared with ox-LDL group, ox-LDL+shMALAT1 group the contents of total cholesterol and triglyceride, apoptosis, IL-6, TNFα and MCP-1, and the expression of NLRP3, RIPK1, caspase-8, p-p65 and SR-A all significantly decreased(P＜0.05). Conclusions MALAT1 may play an important role in ox-LDL-induced cell injury by regulating NLRP3 inflammatory corpuscles and related signal pathways. Knockdown of MALAT1 can significantly reduce the inflammatory reaction and cell damage induced by ox-LDL, which provides a potential target for the treatment of atherosclerosis.

Key words: atherosclerosis, metastasis-associated lung adenocarcinoma transcript 1(MALAT1), Nod-like receptor protein 3 (NLRP3), inflammation

中图分类号:

R543.5

宋宁, 罗俊一, 冀伟, 李艳红, 李晓梅, 杨毅宁. 敲降MALAT1减轻ox-LDL诱导的巨噬细胞炎性反应和细胞损伤[J]. 基础医学与临床, 2026, 46(3): 352-358.

SONG Ning, LUO Junyi, JI Wei, LI Yanhong, LI Xiaomei, YANG Yining. Knock-down MALAT1 reduces ox-LDL- induced-inflammation and cell damage of macrophages[J]. Basic & Clinical Medicine, 2026, 46(3): 352-358.

参考文献 12

[1]	You FF, Gao J, Gao YN, et al. Association between atherogenic index of plasma and all-cause mortality and specific-mortality: a nationwide population-based cohort study[J]. Cardiovasc Diabetol, 2024, 23: 276. doi:10.1186/S12933-024-02370-4.
[2]	Lampsas S, Xenou M, Oikonomou E, et al. Lipoprotein(a) in atherosclerotic diseases: from pathophysiology to diagnosis and treatment[J]. Molecules, 2023, 28: 969. doi: 10.3390/MOLECULES28030969.
[3]	Zeng W, Wu D, Sun Y, et al. The selective NLRP3 inhibitor MCC950 hinders atherosclerosis development by attenuating inflammation and pyroptosis in macrophages. Sci Rep. 2021, 29;11:19305. doi: 10.1038/S41598-021-98437-3.
[4]	Taghvimi S, Soltani Fard E, Khatami SH, et al. lncRNA HOTAIR and cardiovascular diseases[J]. Funct Integr Genomics, 2024, 24: 165. doi: 10.1007/S10142-024-01444-6.
[5]	Blevins HM, Xu Y, Biby S, et al. The NLRP3 inflammasome pathway: a review of mechanisms and inhibitors for the treatment of inflammatory diseases[J]. Front Aging Neurosci, 2022, 14: 879021. doi: 10.3389/FNAGI.2022.879021.
[6]	Lu N, Cheng W, Liu D, et al. NLRP3-mediated inflammation in atherosclerosis and associated therapeutics[J]. Front Cell Dev Biol, 2022, 10: 823387. doi: 10.3389/FCELL.2022.823387.
[7]	Bhansali S, Yadav AK, Bakshi C, et al. Interleukin-35 mitigates ox-ldl-induced proatherogenic effects via modulating mirnas associated with coronary artery disease (CAD)[J]. Cardiovasc Drugs Ther, 2023, 37: 667-682.
[8]	Bai W, Huo T, Chen X, et al. Sacubitril/valsartan inhibits oxLDLinduced MALAT1 expression, inflammation and apoptosis by suppressing the TLR4/NFkappaB signaling pathway in HUVECs[J]. Mol Med Rep, 2021, 23: 1-8.
[9]	Tyrrell D J, Goldstein DR. Ageing and atherosclerosis: vascular intrinsic and extrinsic factors and potential role of IL-6[J]. Nat Rev Cardiol, 2021, 18: 58-68.
[10]	Zeng W, Wu D, Sun Y, et al. The selective NLRP3 inhibitor MCC950 hinders atherosclerosis development by attenuating inflammation and pyroptosis in macrophages[J]. Sci Rep, 2021, 11: 19305. doi:10.1038/S41598-021-98437-3.
[11]	Sharma BR, Karki R, Rajesh Y, et al. Immune regulator IRF1 contributes to ZBP1-, AIM2-, RIPK1-, and NLRP12-PANoptosome activation and inflammatory cell death (PANoptosis)[J]. J Biol Chem, 2023, 299: 105141. doi: 10.1016/J.JBC.2023.105141.
[12]	Huang X, Liu Y, Liu X, et al. OTUB1 facilitates lipid accumulation in oxLDL-induced THP-1 macrophages by stabilizing scavenger receptor-A[J]. IUBMB Life, 2025, 77: e70012.doi:10.1002/iub.70012.

[1]	刘翠玲, 于树娜. NLRP3炎性小体在肝缺血/再灌注损伤中作用的研究进展[J]. 基础医学与临床, 2026, 46(7): 1004-1008.
[2]	王勇豪, 张卓钰, 苏铭恒, 张琪. 外泌体在卒中后认知障碍诊疗中的研究进展[J]. 基础医学与临床, 2026, 46(6): 861-865.
[3]	张腾宇, 吴婷, 吴祥. 视黄酸在认知障碍类疾病中的研究进展[J]. 基础医学与临床, 2026, 46(5): 717-720.
[4]	武懿, 夏丽坤. 嗅素蛋白4调控免疫炎性反应的研究进展[J]. 基础医学与临床, 2026, 46(4): 587-591.
[5]	尹静, 陈春玲. 神经炎性反应介导的术后认知功能障碍的研究进展[J]. 基础医学与临床, 2026, 46(4): 602-606.
[6]	任磊磊, 吕钰麟, 王浩骅, 张婉君, 孟姝, 姜明红. 皮肌炎患者NK细胞衰老介导其“高炎性反应-弱抗感染”的矛盾表型[J]. 基础医学与临床, 2026, 46(3): 345-351.
[7]	何萍, 王艳. Isthmin-1对糖脂代谢的调控作用及其临床意义[J]. 基础医学与临床, 2026, 46(3): 445-449.
[8]	崔宇頔, 张丰川, 李元文, 杨碧莲. 青石止痒软膏减轻咪喹莫特诱导的银屑病小鼠皮肤损伤[J]. 基础医学与临床, 2026, 46(2): 164-169.
[9]	屈改茹, 席世兵, 张宗丽, 李涛. 槲皮素抑制TNF-α诱导的小鼠主动脉血管平滑肌细胞系MOVAS炎性反应[J]. 基础医学与临床, 2026, 46(1): 78-84.
[10]	刘婷婷, 郜玲, 李筱妍. 中性粒细胞胞外诱捕网在脓毒症诱导的急性呼吸窘迫综合征中的研究进展[J]. 基础医学与临床, 2026, 46(1): 139-143.
[11]	周淇, 孙许涛, 吴思雨, 瞿瑛, 宋运佳. Sp1翻译后修饰在动脉粥样硬化中的作用[J]. 基础医学与临床, 2026, 46(1): 134-138.
[12]	李楠, 张贵涛, 王彬, 冯瑶, 李淑娟, 周瑛华. 炎性反应相关指标与院内症状性卒中患者不良预后相关[J]. 基础医学与临床, 2025, 45(8): 1083-1087.
[13]	印华润, 赵宁, 吴志远, 李拥军, 尹洪超. 皮肤桥蛋白通过IL-1β-COL1A1轴促进腹主动脉瘤发展[J]. 基础医学与临床, 2025, 45(7): 918-925.
[14]	张芳龄, 张湲钫, 张立. 右美托咪定减轻丙泊酚诱导的新生大鼠神经损伤[J]. 基础医学与临床, 2025, 45(5): 644-650.
[15]	刘宇涵, 王莹莹, 王钰铖, 郭磊, 鞠瑞. 敲除Mcart1加重脓毒症模型小鼠巨噬细胞炎性反应水平[J]. 基础医学与临床, 2025, 45(5): 616-621.

敲降MALAT1减轻ox-LDL诱导的巨噬细胞炎性反应和细胞损伤

Knock-down MALAT1 reduces ox-LDL- induced-inflammation and cell damage of macrophages

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献 12

相关文章 15

编辑推荐

Metrics

本文评价