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OA
Fucoidan Sulfate and Indobufen Ameliorate High-Fat-Induced CAD via TLR4/NF-κB/NLRP3 Pathway
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.
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.
谢伟;方超华;陈枫楠;沈凯;关丽萍
浙江海洋大学 食品与药学学院,浙江 舟山 316000浙江海洋大学 食品与药学学院,浙江 舟山 316000舟山市妇女儿童医院心内科,浙江 舟山 316000舟山市妇女儿童医院心内科,浙江 舟山 316000浙江海洋大学 食品与药学学院,浙江 舟山 316000
医药卫生
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
fucoidanindobufencoronary atherosclerotic heart diseaseTLR4/NF-κB/NLRP3 signaling pathwaypyroptosis
《海南师范大学学报（自然科学版）》 2026 (2)
192-199,8
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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