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

[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.

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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

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