首页|丹参来源纳米囊泡通过PPAR-γ/LXR-α/ABCA1信号通路抑制平滑肌细胞泡沫化

丹参来源纳米囊泡通过PPAR-γ/LXR-α/ABCA1信号通路抑制平滑肌细胞泡沫化

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目的:探讨丹参来源纳米囊泡(SDNV)通过氧化物酶体增殖物激活受体γ(PPAR-γ)/肝X受体α(LXR-α)/三磷酸腺苷结合盒转运体A1(ABCA1)信号通路抑制氧化低密度脂蛋白(ox-LDL)诱导的平滑肌细胞源性泡沫细胞形成的作用机制.方法:采用透射电镜、纳米颗粒跟踪分析对超高速差速离心法提取的SDNV进行鉴定;选择MOVAS小鼠主动脉血管平滑肌细胞株和ox-LDL诱导建立泡沫细胞模型;通过激光共聚焦观察MOVAS细胞对SDNV的摄取情况;采用CCK8法检测SDNV对MOVAS细胞存活率的影响;将细胞分为对照组、模型组、SDNV组及辛伐他汀组,微板法检测各组细胞内总胆固醇(TC)、游离胆固醇(FC)、胆固醇酯(CE)含量,并计算CE/TC比值;油红O染色观察各组细胞内脂质蓄积的情况;Western Blot分析各组细胞中PPAR-γ、LXR-α、ABCA1蛋白表达水平.结果:SDNV通过透射电镜、纳米颗粒跟踪分析鉴定SDNV符合纳米囊泡的表征及粒径要求;激光共聚焦观察到SDNV可以被MOVAS细胞摄取;CCK8实验结果显示SDNV对MOVAS细胞无明显毒性;油红O染色及CE/TC值的改变表明SDNV能够抑制MOVAS细胞的脂质蓄积,抑制泡沫细胞的形成;与模型组比较,SDNV组PPAR-γ、LXR-α、ABCA1蛋白表达水平显著升高(P＜0.01).结论:SDNV可以通过PPAR-γ/LXR-α/ABCA1信号通路抑制平滑肌源性泡沫细胞的形成,进而防治动脉粥样硬化.
Salvia miltiorrhiza-derived nanometer vesicles mitigate foam production of vascular smooth muscle cell via PPAR-γ/LXR-α/ABCA1 signal pathway
Objective:To investigate the mechanism by which Salvia miltiorrhiza-derived nanometer vesicles(SDNV)inhibit the formation of smooth muscle cell-derived foam cells induced by oxidized low density lipoprotein(ox-LDL)via the PPAR-γ/LXR-α/ABCA1 signal pathway.Methods:Transmission electron microscopy and nanoparticle tracking analysis were used to identify SDNV extracted by ultra-high speed differential centrifugation method.The foam cell model was established by using MOVAS mouse aortic smooth muscle cell line and oxidized low density lipoprotein.The uptake of SDNV by MOVAS cells was observed by confocal laser.The effect of SDNV on the survival rate of MOVAS cells was detected by CCK8 method.The cells were divided into control group,model group,SDNV group and simvastatin group.The contents of total cholesterol(TC),free cholesterol(FC)and cholesteryl ester(CE)in each group were detected by microplate method,and the CE/TC ratio was calculated.The intracellular lipid accumulation in each group was observed by oil red O staining.The protein expression levels of PPAR-γ,LXR-α and ABCA1 in cells of each group were analyzed by Western Blot.Results:SDNV was identified by transmission electron microscopy and nanoparticle tracking analysis to meet the requirements of characterization and particle size of nanovesicles.The laser confocal observation showed that SDNV could be taken up by MOVAS cells.The results of CCK8 experiment showed that SDNV had no obvious toxicity to MOVAS cells.Oil red O staining and CE/TC values showed that SDNV could inhibit the accumulation of lipids and the formation of foam cells in MOVAS cells.Compared with the model group,the protein expression levels of PPAR-γ,LXR-α and ABCA1 in SDNV group significantly increased(P＜0.01).Conclusion:SDNV can inhibit the formation of smooth muscle derived foam cells through PPAR-γ/LXR-α/ABCA1 signal pathway,and then prevent atherosclerosis.

Salvia miltiorrhizaNanometer vesiclesSmooth muscle cellFoam cellOxidized low density lipoprotein(ox-LDL)MechanismAtherosclerosis(AS)PPAR-γ/LXR-α/ABCA1 signal pathway

张林琦、武若愚、徐红俊、陈鸿旭、安胜军

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河北中医药大学,石家庄 050200

丹参 纳米囊泡 平滑肌 泡沫细胞 氧化低密度脂蛋白 机制 动脉粥样硬化 氧化物酶体增殖物激活受体γ/肝X受体α/三磷酸腺苷结合盒转运体A1信号通路

国家自然科学基金项目河北省中医药管理局科研计划项目河北省重点研发计划项目河北省自然科学基金中医药联合基金重点项目

822046582019073213777100DH2022423319

2024

中华中医药杂志
中华中医药学会

中华中医药杂志

CSTPCD北大核心
影响因子：1.135
ISSN：1673-1727
年,卷(期)：2024.39(7)
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