| 谢伟, 方超华, 陈枫楠, 沈凯, 关丽萍.岩藻聚糖硫酸酯联合吲哚布芬经TLR4/NF-κB/NLRP3通路改善高脂诱导冠心病的机制[J].海南师范大学学报自科版,2026,(2):192-199 |
| 岩藻聚糖硫酸酯联合吲哚布芬经TLR4/NF-κB/NLRP3通路改善高脂诱导冠心病的机制 |
| Fucoidan Sulfate and Indobufen Ameliorate High-Fat-Induced CAD via TLR4/NF-κB/NLRP3 Pathway |
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| DOI：10.12051/j.issn.1674-4942.2024.04.010 |
| 中文关键词: 岩藻聚糖硫酸酯 吲哚布芬 冠状动脉粥样硬化性心脏病 TLR4/NF-κB/NLRP3信号通路 细胞焦亡 |
| 英文关键词: fucoidan indobufen coronary atherosclerotic heart disease TLR4/NF-κB/NLRP3 signaling pathway pyroptosis |
| 基金项目:浙江省医学会临床医学科研专项资金项目（2023ZYC-A65）；舟山市医药卫生科技计划项目（2023YA10） |
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| 中文摘要: |
| 本文探讨岩藻聚糖硫酸酯联合吲哚布芬通过抑制TLR4/NF-κB/NLRP3信号通路介导的细胞焦亡改善高脂诱导冠状动脉粥样硬化性心脏病（CAD）的作用机制，为CAD的海洋药物防治提供理论依据。采用高脂饲料喂养联合垂体后叶素诱导建立大鼠CAD模型，体外使用LPS诱导人冠状动脉内皮细胞（HCAEC）炎症模型。将大鼠随机分为空白组、高血脂+冠心病组、岩藻聚糖硫酸酯+吲哚布芬组（n = 8）。通过检测血脂指标（TC、TG、HDL-C、LDL-C）、细胞活性（MTT法）、一氧化氮（NO）水平、脂滴数量（油红O染色），利用Western Blot法检测TLR4、NLRP3、p-p65蛋白表达，评估药物效果。结果表明：与空白组比较，高血脂+冠心病组血清TC、TG、LDL-C水平显著升高（P < 0.05），HDL-C降低（P < 0.05），NO浓度上升（P < 0.05），且细胞形态改变（弯曲呈圆环形）和脂滴积累明显；与高血脂+冠心病组比较，联合用药组血清TC ［（2.81±1.31） vs. （3.86±0.92） mmol/L］、TG ［（1.57±0.59 ）vs. （2.13±1.09） mmol/L］、LDL-C［（1.13±0.95） vs. （1.80±1.06） mmol/L］显著降低（P < 0.05），HDL-C显著升高［（1.11±0.72） vs. （0.97±1.04） mmol/L，P < 0.05］，NO浓度显著下降（P < 0.05），细胞形态恢复（细长梭形），脂滴减少；同时，TLR4、NLRP3、p-p65蛋白表达显著被抑制（P < 0.05）。岩藻聚糖硫酸酯（1 mg/mL）联合吲哚布芬（10 μmol/L）通过抑制TLR4/NF-κB/NLRP3信号通路介导的细胞焦亡有效改善高脂诱导CAD，为海洋药物防治心血管疾病提供了新途径。 |
| 英文摘要: |
| This study investigated the mechanism by which fucoidan sulfate combined with indobutfen improved hyperlipidemia-induced coronary artery disease (CAD) by inhibiting cell pyroptosis mediated through the TLR4/NF-κB/NLRP3 signaling pathway, providing a theoretical basis for marine-based therapeutic interventions in CAD. A rat CAD model was established using a high-fat diet combined with pituitrin administration, while an in vitro inflammatory model was induced in human coronary artery endothelial cells (HCAEC) with LPS. Rats were randomly divided into a control group, a hyperlipidemia + coronary artery disease group, and a fucoidan sulfate + indobutafen group (n = 8). Drug efficacy was evaluated by measuring lipid parameters (TC, TG, HDL-C, LDL-C), cellular viability (MTT assay), nitric oxide (NO) levels, lipid droplet formation (oil red O staining), and protein expression levels of TLR4, NLRP3, and p-p65 via Western blot. The results demonstrated that, compared with the control group, the hyperlipidemia + coronary artery disease (CAD) group exhibited significantly elevated serum levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) (P < 0.05), decreased high-density lipoprotein cholesterol (HDL-C) (P < 0.05), and increased nitric oxide (NO) concentration (P < 0.05), along with marked cellular morphological changes (curved and annular shapes) and lipid droplet accumulation. Compared with the hyperlipidemia + CAD group, the combined drug therapy group showed significantly reduced serum TC [(2.81 ± 1.310) vs. (3.86 ± 0.92) mmol/L], TG [(1.57 ± 0.59) vs. (2.13 ± 1.09) mmol/L], and LDL-C [(1.13 ± 0.95) vs. (1.80 ± 1.06) mmol/L] (P <0.05), elevated HDL-C [(1.11 ± 0.72) vs. (0.97 ± 1.04) mmol/L, P <0.05], decreased NO concentration (P <0.05), restored cellular morphology (elongated spindle-shaped), and reduced lipid droplet accumulation. Additionally, protein expression of TLR4, NLRP3, and p-p65 was significantly inhibited (P < 0.05). Fucoidan sulfate (1 mg/mL) combined with indobutfen (10 μmol/L) effectively improved hyperlipidemia-induced CAD by inhibiting cell pyroptosis mediated through the TLR4/NF-κB/NLRP3 signaling pathway, providing a novel approach for marine-based therapeutic interventions in cardiovascular diseases. |
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