戊糖片球菌ATCC33316通过上调肠道中吲哚3丙酮酸改善ApoE-/-小鼠动脉粥样硬化

    Pediococcus pentosaceus ATCC33316 ameliorates atherosclerosis in ApoE-/- mice by upregulating indol-3-yl pyruvic acid in the intestine

      摘要
    • 摘要:
      目的 探讨口服益生菌在改善动脉粥样硬化过程中的作用及其分子机制。
      方法 体内实验：将高脂高胆固醇饲料喂养的雄性载脂蛋白E基因敲除（ApoE-/-）小鼠分为PBS组与ATCC33316组，PBS组灌胃无菌PBS，ATCC33316组灌胃戊糖片球菌ATCC33316。观察主动脉病变程度，检测血脂及血清中肿瘤坏死因子-alpha（tumor necrosis factor-alpha，TNF-α)、白细胞介素-6(interleukin 6，IL-6)及IL-10水平；非靶向代谢组学技术分析小鼠结肠（含内容物）。体外实验：采用50 mg/L 氧化低密度脂蛋白（oxidized low-density lipoprotein，ox-LDL）诱导THP-1源性的巨噬细胞建立泡沫细胞模型组，在此基础上加入1 mmol/L吲哚3丙酮酸（indol-3-yl pyruvic acid，I3P）作为给药组，观察细胞脂质蓄积。M1极化细胞模型中，将THP-1源性的巨噬细胞分为M0组、M1组（20 ng/mL IFN-γ + 100 ng/mL LPS）与M1+I3P组（1 mmol/L I3P + 20 ng/mL IFN-γ + 100 ng/mL LPS），通过qRT-PCR分析各组 IL-1β及TNF-α的表达，检测细胞上清液中IL-1及TNF-α水平。
      结果 ①体内实验：ATCC33316组主动脉及主动脉窦斑块病变程度减轻（P<0.01，P<0.05），甘油三酯（P<0.01）、TNF-α及IL-6（P<0.05）水平下降，IL-10（P<0.05）水平升高，肠道中I3P水平上调（P<0.05）。②体外实验：I3P处理抑制泡沫细胞模型中细胞的脂滴累积（P<0.01），降低了M1极化细胞模型中IL-1β及TNF-α的表达及上清液中IL-1及TNF-α水平（P<0.01）。
      结论 戊糖片球菌ATCC33316可通过上调I3P水平减轻炎症，从而改善动脉粥样硬化病变。

       

      Abstract:
      AIM To investigate the role of oral probiotics in ameliorating the process of atherosclerosis and its molecular mechanism.
      METHODS In vivo experiments: Male apolipoprotein E knockout (ApoE-/-) mice fed with high-fat and high-cholesterol diets were divided into PBS group and ATCC33316 group; PBS group was fed with sterile PBS by gavage and ATCC33316 group was fed with pediococcus pentosaceus ATCC33316 by gavage. The extent of aortic lesions was observed; blood lipids and serum tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6) and IL-6 were detected; untargeted metabolomics techniques were used to analyze these mouse colons (with contents). In vitro experiments: THP-1-derived macrophages were induced by 50 mg/L oxidized low-density lipoprotein (ox-LDL) to establish a foam cell model group, to which 1 mmol/L indol-3-yl pyruvic acid (I3P) was added as the drug-delivery group, cellular lipid accumulation was observed. In the M1-polarised cell model, THP-1-derived macrophages were divided into M0 group, M1 group (20 ng/mL IFN-γ+100 ng/mL LPS) and M1+I3P group (1 mmol/L I3P+ 20 ng/mL IFN-γ+ 100 ng/mL LPS), and the expression of IL-1β and TNF-α were analyzed in each group by qRT-PCR, and the levels of IL-1 and TNF-α were detected in the cell supernatant.
      RESULTS ①In vivo experiments: In ATCC33316 group, the extent of aortic and aortic sinus plaque lesions was reduced (P<0.01, P<0.05), triglyceride (P<0.01), TNF-α, and IL-6 levels (P<0.05) were decreased, IL-10 levels (P<0.05) were elevated and I3P levels were upregulated in the intestine (P<0.05). ② In vitro experiments: I3P treatment inhibited the accumulation of lipid droplets in cells in the foam cell model (P<0.01) and decreased the expression of IL-1β and TNF-α and the levels of IL-1 and TNF-α in the supernatant in the M1 polarized cell model (P<0.01).
      CONCLUSION Pediococcus pentosaceus ATCC33316 reduces inflammation by up-regulating I3P levels, thereby ameliorating atherosclerotic lesions.

       

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