姜黄素通过影响巨噬细胞的极性延缓动脉粥样硬化进展

Curcumin alleviates the progression of atherosclerosis through its action on macrophage polarization

目的研究姜黄素对ApoE基因敲除(ApoE^(-/-))小鼠动脉粥样硬化进展及斑块中巨噬细胞极性的影响。方法用高脂高胆固醇饮食饲养ApoE^(-/-)小鼠建立动脉粥样硬化模型,设立姜黄素治疗组、阿托伐他汀治疗组和高脂组;通过免疫组织化学(HE染色、油红O染色、Masson染色、苏木精染色)及免疫荧光染色检测主动脉斑块形态及不同亚型巨噬细胞的含量。通过实时荧光定量PCR检测主动脉组织中炎症因子的表达。结果姜黄素干预能减轻ApoE^(-/-)小鼠主动脉粥样硬化病变,并降低动脉粥样硬化斑块的易损指数。姜黄素降低动脉粥样硬化斑块内M1/M2巨噬细胞的比值,减少M1型巨噬细胞分泌的促炎因子白细胞介素1β(IL-1β)、诱导型一氧化氮合酶(iNOS)和肿瘤坏死因子α(TNF-α)的表达,促进M2型细胞因子IL-10、Ym1和Fizz1的表达。结论姜黄素可通过影响斑块中巨噬细胞的极性、抑制相关的炎症反应,从而延缓ApoE^(-/-)小鼠动脉粥样硬化的进展。

Aim To investigate the effect of curcumin on the progression of atherosclerosis and macrophage polarization in vivo. Methods The apolipoprotein E deficient (ApoE^-/-) mice were fed with high fat diet to establish atherosclerosis model. The aortas were isolated for haematoxylin and eosin, masson trichrome, picrosirus red, oil red O and immunofluorescence staining. Inducible nitric oxide synthase (iNOS) and CD206 were utilized as biomarkers of M1 and M2 phenotypes, respectively. Quantitative real-time polymerase chain reaction (PCR) was carried out to examine the gene expression of inflammatory factors. Results Curcumin significantly decreased atherosclerotic burden and plaque vulnerability in the experimental atherosclerosis model. Furthermore, curcumin decreased the ratio of M1/M2 macrophages together with the gene expressions of pro-inflammatory interleukin 1beta (IL-1β), inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), but promoted the levels of anti-inflammatory cytokines IL-10, Ym1, Fizz1 in the atherosclerotic plaque. Conclusion Curcumin could alleviate the progression of atherosclerosis by inhibiting macrophage polarizing towards M1 phenotype as well as inflammatory response.