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芦荟苷通过调控巨噬细胞极化改善动脉粥样硬化的机制研究
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| 篇名： | 芦荟苷通过调控巨噬细胞极化改善动脉粥样硬化的机制研究 |
| TITLE： | Mechanism of aloin ameliorating atherosclerosis through regulating macrophage polarization |
| 摘要： | 目的 探究芦荟苷（ALO）改善动脉粥样硬化（AS）的机制。方法将8只C57BL/6J小鼠设为对照组（CON组），基础饲料喂养；将32只载脂蛋白E基因敲除（APOE－/－）小鼠随机分为模型组（MOD组），ALO低、高剂量组[ALO-L、ALO-H组，20、40mg/（kg·d）]、阿托伐他汀阳性对照组[ATO组，4mg/（kg·d）]，每组8只，通过高脂饲料喂养构建AS小鼠模型。各组小鼠灌胃给药或等体积去离子水，持续8周。检测小鼠血脂水平，观察其主动脉病理结构变化，检测其主动脉中CD86+、CD206+表达，并检测其主动脉中诱导型一氧化氮合酶（iNOS）、肿瘤坏死因子α（TNF-α）、精氨酸酶1（Arg-1）、白细胞介素10（IL-10）mRNA和iNOS、Arg-1蛋白表达以及核因子κBp65（NF-κBp65）、信号转导和转录激活因子3（STAT3）蛋白的磷酸化水平。以脂多糖（LPS）诱导RAW264.7细胞构建巨噬细胞极化模型，考察ALO（400μmol/L）对巨噬细胞极化的影响。结果与MOD组相比，各给药小鼠的血脂（除ALO-L组小鼠血清中高密度脂蛋白胆固醇外）异常均被显著逆转（P＜0.05），主动脉内膜结构亦明显改善，斑块面积均显著缩小（P＜0.01），主动脉中CD86+相对荧光强度均显著降低、CD206+相对荧光强度均显著升高（P＜0.01），iNOS、TNF-αmRNA表达水平均显著降低（P＜0.05）；ALO-H组、ATO组小鼠主动脉中Arg-1、IL-10mRNA及Arg-1蛋白表达水平均显著升高（P＜0.05），iNOS蛋白表达水平及NF-κBp65、STAT3蛋白的磷酸化水平均显著降低（P＜0.05）。细胞实验结果显示，ALO可显著降低LPS诱导的M1型巨噬细胞比例（P＜0.01），升高M2型巨噬细胞比例（P＜0.01）。结论ALO可抑制巨噬细胞向M1型极化并促进其向M2型极化，改善AS模型小鼠血脂代谢紊乱，减少主动脉斑块形成，改善主动脉内膜结构；该作用机制可能与抑制NF-κB/STAT3信号通路有关。 |
| ABSTRACT： | OBJECTIVE To investigate the mechanism by which aloin （ALO） ameliorates atherosclerosis （AS）. METHODS Eight C57BL/6J mice were assigned to the control group （CON group） and fed a standard diet； thirty-two apolipoprotein E-knockout （APOE－/－） mice were randomly divided into model group （MOD group）， ALO low-dose and high-dose groups [ALO-L group， ALO-H group， 20， 40 mg/（kg·d）]， and atorvastatin positive control group [ATO group， 4 mg/（kg·d）]， with 8 mice in each group， establishing the AS model through feeding with a high-fat diet. The mice were administered the drug via gavage or given an equal volume of deionized water for 8 consecutive weeks. The lipid levels in the serum of mice were measured， and the pathological structural changes in their aortas were observed. The expressions of macrophage polarization markers （CD86+ ， CD206+） in the aorta were determined， along with the mRNA expressions of inducible nitric oxide synthase （iNOS）， tumor necrosis factor-α （TNF-α）， arginase-1 （Arg-1）， and interleukin-10 （IL-10）， as well as the protein expressions of iNOS and Arg- 1， and the phosphorylation levels of nuclear factor κB p65 （NF-κB p65） and signal transduction and activator of transcription 3 （STAT3） proteins. Additionally， a macrophage polarization model was established using lipopolysaccharide （LPS）-induced RAW264.7 cells， and the effect of ALO （400 μmol/L） on the cellular polarization phenotype was investigated. RESULTS Compared with the MOD group， administration groups all showed significant improvement in dyslipidemia （except for high-density lipoprotein cholesterol in the serum of ALO-L group） （P＜0.05）； aortic intimal structure improved significantly， plaque area was reduced significantly （P＜0.01）； the CD86+ relative fluorescence intensity in the aorta decreased significantly， the CD206+relative fluorescence intensity increased significantly （P＜0.01）， while the expressions of iNOS and TNF-α mRNA were down-regulated significantly （P＜0.05）； mRNA expressions of Arg-1 and IL-10， and protein expression of Arg-1 were increased significantly in ALO-H group and ATO group （P＜0.05）； the protein expressions of iNOS， and the phosphorylation levels of NF-κB p65 and STAT3 protein were decreased significantly （P＜0.05）. In vitro experiments further confirmed that ALO significantly reduced the proportion of LPS-induced M1-type macrophages but increased the proportion of M2-type macrophages （P＜0.01）. CONCLUSIONS ALO inhibits M1-type macrophage polarization and promotes M2-type polarization， ameliorates dyslipidemia and reduces arterial plaque formation in AS model mice， improve the structure of the aortic intima potentially through suppression of the NF-κB/STAT3 signaling pathway. |
| 期刊： | 2025年第36卷第22期 |
| 作者： | 田野；陈线茹；梅向辉；李百超；杜文涛 |
| AUTHORS： | TIAN Ye，CHEN Xianru，MEI Xianghui，LI Baichao，DU Wentao |
| 关键字： | 芦荟苷；动脉粥样硬化；巨噬细胞极化；NF-κB/STAT3信号通路 |
| KEYWORDS： | aloin； atherosclerosis； macrophage polarization； NF-κB/STAT3 signaling pathway |
| 阅读数： | 1 次 |
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