宁心涤痰汤通过STAT1/LXR-α通路介导的巨噬细胞内质网应激治疗支架内再狭窄的机制研究  

Mechanism of Ningxin Ditan Decoction Improves In-stent Restenosis by Inhibiting Macrophage Endoplasmic Reticulum Stress through STATi/LXR-αPathway

作　　者：曹丽娟[1,2] 于玲 刘莉 Cao Lijuan;Yu Ling;Liu Li(Heilongjiang University of Chinese Medicine,Heilongjiang,Harbin 150006,China)

机构地区：[1]黑龙江中医药大学,黑龙江哈尔滨150006 [2]黑龙江省齐齐哈尔市中医医院,黑龙江齐齐哈尔161099 [3]广东省中医院,广东广州510120 [4]黑龙江中医药大学附属第一医院,黑龙江哈尔滨150040

出　　处：《中国中医急症》2023年第6期969-973,共5页Journal of Emergency in Traditional Chinese Medicine

基　　金：国家自然科学基金青年科学基金项目(82104962);黑龙江省青年人才托举工程项目(2022-QNRC1-28)。

摘　　要：目的观察宁心涤痰汤对STAT1/LXR-α信号通路介导的巨噬细胞内质网应激的影响,从而阐明其抑制支架内再狭窄的分子机制。方法人急性单核细胞白血病细胞(THP-1)体外诱导分化成巨噬细胞后分为空白组、模型组、宁心涤痰汤组和辛伐他汀组。通过ox-LDL诱导构建泡沫细胞模型,并给予相应的药物进行干预。分别采用Western blotting和ELISA法检测各组巨噬细胞STAT1/LXR-α通路与内质网应激相关蛋白的表达水平和炎症因子的含量。构建巨噬细胞与血管平滑肌细胞共培养体系,通过CCK8法和划痕实验检测各组平滑肌细胞增殖和迁移能力的改变。结果与空白组相比,模型组巨噬细胞中p-STAT1、p-PERK、p-elf2α及CHOP蛋白的表达及细胞上清中肿瘤坏死因子-6(IL-6)、人单核细胞趋化蛋白-1(MCP-1)和肿瘤坏死因子-α(TNF-α)的含量均显著升高,LXR-α蛋白表达显著降低,差异有统计学意义(P<0.01);与模型组比较,宁心涤痰汤组能够显著抑制巨噬细胞中p-STAT1、p-PERK、p-elf2α及CHOP蛋白的表达和上清中IL-6、MCP-1和TNF-α的含量,上调LXR-α蛋白的表达,差异均有统计学意义(P<0.05或P<0.01)。此外,与空白组相比,模型组平滑肌细胞增殖与迁移率显著增加(P<0.01);与模型组比较,宁心涤痰汤组能够显著抑制平滑肌细胞增殖与迁移率,差异均有统计学意义(P<0.01)。结论宁心涤痰汤通过促进STAT1/LXR-α通路的活化从而抑制巨噬细胞内质网应激,达到治疗PCI后支架内再狭窄的作用。Objective:To observetheeffectsof Ningxin Ditan Decoction on endoplasmic reticulumstressof macrophages and vascular smooth muscle phenotype mediated by STAT1/LXR-αsignaling pathway,and to eluci-date the molecular mechanism of inhibiting in-stent restenosis.Methods:THP-1 was induced to differentiate in-to macrophages in vitro,and were divided into the control group,model group,Ningxin Ditan Decoction group and simvastatin group.In addition to the control group,the remaining groups were induced by oxidized low-density li-poprotein(ox-LDL)to build a foam cell model,and the corresponding drug containing serum was given for inter-vention.Western blotting and ELISA were used to detect the expression levels of related proteins in STAT1/LXR-αpathway and endoplasmic reticulum stress and the content of inflammatory factors in macrophages.Macrophages from the above groups were extracted and co-cultured with vascular smooth muscle cells.The changes of prolifera-tion and migration ability of smooth muscle cells in each group were detected by CCK8 method and scratch test re-spectively.Results:Compared with the control group,the expression of p-SATA1,p-PERK,p-elf2a and CHOP proteins in macrophages and the contents of IL-6,MCP-1 and TNF-αin supernatant in model group were signifi-cantly increased,while the expression of LXR-a protein was significantly decreased,the differences were statisti-cally significant(P<0.01).Compared with the model group,Ningxin Ditan Decoction significantly inhibited the ex-pression of p-SATA1,p-PERK,p-elf2a and CHOP proteins in macrophages and the contents of IL-6,MCP-1 and TNF-αin supernatant,and upregulated the expression of LXR-a proteins,the differences were statistically sig-nificant(P<0.05 and P<0.01).In addition,compared with the control group,the proliferation and mobility of smooth muscle cells in model group were significantly increased(P<0.01).Compared with model group,Ningxin Ditan Decoction could significantly inhibit proliferation and mobility of smooth muscle cell,and the differences

关 键 词：支架内再狭窄 宁心涤痰汤 巨噬细胞 内质网应激 STAT1/LXR-α信号通路 

分 类 号：R285.5[医药卫生—中药学]