基于肠道菌群和短链脂肪酸代谢探讨不同饮食条件下高脂血症大鼠发病机制
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1.甘肃农业大学动物医学院;2.山东省中医药研究院

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Study on the pathogenesis of hyperlipidemia rats under different dietary conditions based on intestinal flora and short-chain fatty acid metabolism
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1.College of Veterinary medicine,Gansu Agriculture University;2.Shandong Academic of Chinese Medicine;3.Shandong Institute of traditional Medicine

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    摘要:

    目的 本研究拟对比两种不同高脂饮食方式诱导的高脂血症大鼠肠道菌群变化与短链脂肪酸代谢特征,以宿主-肠道菌群-代谢角度探讨高脂血症可能的微观机制。 方法 SPF级SD大鼠分为:(1)正常饮食组(CG组),饲喂大鼠维持饲料(2)高脂饮食组(HFD1组),每天足量饲喂高脂饲料,(3)限饲高脂饮食组(HFD2组),每天限量饲喂高脂饲料80g,不限量饲喂维持饲料。8周后检测血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)水平;苏木精-伊红(HE)染色观察大鼠肝脏组织和肾周脂肪病理学变化;取结肠内容物进行16S rRNA高通量测序,观察肠道菌群结构与功能的变化,并检测结肠内容物中短链脂肪酸的含量。结果 与CG组相比较,HFD1组和HFD2组大鼠摄食量下降,体重升高;血清中TC 、TG、LDL-C均显著升高;肝脏组织发生明显脂肪变性,肾周脂肪出现炎性病变;高脂干预后大鼠肠道菌群相对丰度显著变化,其中乳杆菌属相对丰度明显降低,菌群结构和功能变化明显,总短链脂肪酸、乙酸、丁酸、异丁酸下降显著。结论 两种高脂饮食方式均能引起大鼠高脂血症,且发病机制基本一致,均与脂质代谢以及肠道菌群紊乱有关。每日限制一定的高脂饲料饲喂量不仅能够降低高脂饲料对大鼠食欲的影响,还能提高大鼠高脂血症模型制备的稳定性,是一种值得推广应用的大鼠高脂模型制备方法。

    Abstract:

    Objective The purpose of this study was to compare the changes of intestinal flora and the characteristics of short-chain fatty acid metabolism in hyperlipidemic rats induced by two different high-fat diets, and to explore the possible microscopic mechanism of hyperlipidemia from the point of view of host-intestinal flora-metabolism. Methods SPF SD rats were divided into two groups: (1) normal diet group (CG group), fed with high fat diet group (HFD1 group), fed with high fat diet group (HFD1 group), and fed with high fat diet group (HFD2 group). Rats were fed with 80g high fat diet and unlimited maintenance diet.燗fter 8 weeks, the levels of serum total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) were measured, and the pathological changes of liver tissue and perirenal fat were observed by hematoxylin-eosin (HE) staining.燭he contents of colon were taken for 16s rRNA high-throughput sequencing to observe the changes of the structure and function of intestinal flora and the content of short-chain fatty acids in colon contents. Result Compared with CG group, food intake decreased and body weight increased in HFD1 group and HFD2 group, serum TC, TG and LDL-C increased significantly, liver tissue showed obvious steatosis and perirenal fat showed inflammatory lesions. After high-fat intervention, the relative abundance of intestinal microflora in rats changed significantly and there were gender differences, in which the relative abundance of Lactobacillus decreased significantly, and the structure and function of Lactobacillus decreased significantly, including total short-chain fatty acids, acetic acid, butyric acid and isobutyric acid. Conclusion The two kinds of high-fat diet can cause hyperlipidemia in rats, and the pathogenesis is basically the same, which is related to lipid metabolism and intestinal flora disorder. Daily restriction of a certain amount of high-fat diet can not only reduce the effect of high-fat diet on rat appetite, but also improve the stability of rat hyperlipidemia model preparation.

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  • 收稿日期:2023-04-24
  • 最后修改日期:2023-09-25
  • 录用日期:2023-10-19
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