菊粉对ApoE -/-小鼠动脉粥样硬化症的保护作用

Protective Effects of Inulin on Atherosclerosis in ApoE-/- Mice

摘要:

该研究旨在评价菊粉（INU）干预动脉粥样硬化症（AS）的作用及可能机制。8周龄雄性ApoE-\-小鼠随机分为3组：对照组（CON）给予正常饮食，AS组（AS）采用高脂饮食，INU干预组（AS+INU）在AS造模基础上采用INU口服干预。干预12周后，采用病理切片油红O、马松和HE染色评价INU干预AS的效果，16S rRNA测序分析肠道菌群，鲎试剂法检测血浆脂多糖（LPS），流式多重蛋白定量技术（CBA）检测炎症因子，气质联用（GC-MS）检测肠道短链脂肪酸（SCFAs）。结果显示，INU干预缓解了AS脂质斑块沉积、纤维化及病理损害；血浆总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白（LDL）显著降低至14.04 mmol/L、0.35 mmol/L、2.31 mmol/mL（p均<0.05）；Alistipes、Intestinimonas、Bilophila、Oscillibacter、Negativibacillus相对丰度显著减少至1.09×10-3、3.46×10-4、1.86×10-4、1.56×10-4、3.72×10-4（p均<0.05），Faecalibaculum显著增加至0.28（p<0.05）；SCFAs和血浆LPS显著改善；主动脉根部组织和血浆肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1β、IL-6、IL-17A显著降低至27.32和6.59 pg/mL、19.15和4.60 pg/mL、49.81和8.57 pg/mL、16.70和3.57 pg/mL（p<0.05）。该研究表明膳食INU通过调节肠道菌群和抑制炎症改善AS。

Abstract:

In this study, the effects and possible mechanism of inulin (INU) on atherosclerosis (AS) were investigated. Eight-week male ApoE-/- mice were randomly divided into control group (CON), atherosclerosis model group (AS) and INU treatment group (AS+INU), in which CON group fed with a standard chow diet, AS group fed with a high-fat diet, AS+INU group fed with dietary INU based on AS model. After 12 weeks of treatments, oil red O, Masson’s trichrome and HE stainings were used to evaluate the effects of INU on AS, 16S rRNA sequencing analysis was used to determine the community of gut microbiota. Limulus amebocyte lysate method was adopted to measure lipopolysaccharide (LPS) levels in plasma. Flow cytometry multiple proteins cytometric bead array (CBA) was used to measure the inflammatory cytokines. Fecal short-chain fatty acids (SCFAs) were determined using gas chromatography-mass spectrometer (GC-MS) method. The results showed that the lipid acceleration, fibrosis and vascular lesion of aorta plague were attenuated with dietary INU intervention. Total cholesterol (TC) Triglyceride (TG) and low density lipoprotein (LDL) in plasma with INU treatment were separately reduced to 14.04 mmol/L, 0.35 mmol/L, 2.31 mmol/mL, respectively (p<0.05). The gut microbiota was modulated in long-term INU administration by significantly reducing Alistipes (1.09×10-3), Intestinimonas (3.46×10-4), Bilophila (1.86×10-4), Oscillibacter (1.56×10-4), Negativibacillus (3.72×10-4) (p<0.05), as well as intriguingly increasing the relative abundance of Faecalibaculum (0.28) (p<0.05). Moreover, gut mcirobiota-derived SCFAs and plasma translocated LPS were improved with INU treatment. The pro-inflammatory tumor necrosis factor (TNF)-ɑ, interleukin (IL)-1β, IL-6, IL-17A in plasma and aorta root tissuewere notably decreased to 27.32 and 6.59 pg/mL, 19.15 and 4.60 pg/mL, 49.81 and 8.57 pg/mL, 16.70 and 3.57 pg/mL, respectively, in AS with long-term dietary INU intervention(p<0.05). Collectively, this study highlights that INU ameliorates AS via modulating gut microbiota and anti-inflammation.