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嗜黏蛋白阿克曼菌及Amuc_1100对高脂饮食联合链脲佐菌素诱导的糖尿病大鼠的保护作用

Protective Effects of Akkermansia muciniphila and Amuc_1100 Protein on Rats on High-Fat Diet Combined with Streptozotocin Injection

  • 摘要:
      目的  探究嗜黏蛋白阿克曼菌活菌、巴氏灭活菌及Amuc_1100蛋白干预对高脂饮食联合链脲佐菌素(streptozotocin, STZ)诱导的糖尿病大鼠的预防保护作用。
      方法  将96只SD大鼠随机分成8组,包括6组实验组和2组对照组,每组12只。采用高脂饲料喂养联合STZ注射模拟大鼠2型糖尿病进展。同时用不同剂量的嗜黏蛋白阿克曼菌活菌、巴氏灭活菌及Amuc_1100蛋白灌胃干预8周。收集大鼠血浆样本测定脂质和葡萄糖代谢、炎症相关指标因子,收集结肠组织样本进行HE染色。收集大鼠粪便样本进行16S rRNA基因测序。
      结果  与高脂饮食对照组相比,嗜黏蛋白阿克曼菌干预组大鼠体质量增加减少(P<0.01)、血浆肿瘤坏死因子-α水平降低(P<0.05);嗜黏蛋白阿克曼菌或Amuc_1100干预可导致杯状细胞数量和黏蛋白分泌增加。各干预组样本β多样性分析显示总体上无差异。
      结论  口服嗜黏蛋白阿克曼菌可以有效减轻高脂饮食引起的代谢紊乱,包括体质量增加和全身炎症等。嗜黏蛋白阿克曼菌及Amuc_1100干预对改善肠道屏障功能具有一定作用,干预8周后对肠道菌群结构没有明显影响。

     

    Abstract:
      Objective  To explore the protective effects of live or pasteurized Akkermansia muciniphila and Amuc_1100 protein on a rat model of diabetes mellitus induced by high-fat diet (HFD) combined with streptozotocin (STZ).
      Methods  A total of 96 Sprague-Dawley (SD) rats were randomly assigned to 8 groups, including 6 experimental groups and 2 control groups, with 12 rats in each group. HFD combined with STZ injection was given to the rats to create a simulated model of the progression of diabetes mellitus type 2. In addition, the rats were treated with different doses of live or pasteurized Akkermansia muciniphila or Amuc_1100 protein by way of gavage for 8 weeks simultaneously. Plasma samples were collected to determine the level of parameters related to lipid and glucose metabolism, and inflammation mediators. Colon tissue specimens were collected for HE staining. Stool samples of the rats were collected for 16S rRNA gene sequencing.
      Results  Compared with the HFD control group, rats in the group treated with Akkermansia muciniphila exhibited significantly lower body mass gain (P<0.01) and lower plasma TNF-α level (P<0.05). Administration of Akkermansia muciniphila or Amuc_1100 protein increased the number of goblet cells and mucin secretion. The β diversity analysis of the samples showed no overall difference in the intervention groups.
      Conclusion  Oral administration of Akkermansia muciniphila can effectively ameliorate HFD-induced metabolic disorders, including body mass gain and systemic inflammation. Akkermansia muciniphila and Amuc_1100, to a certain degree, improved the gut barrier function. After eight weeks of intervention, there was no significant impact on the structure of the gut microbiota.

     

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