基于肠道菌群调节的GLP-1降糖作用机制研究

目的从肠道群调节角度探讨胰高血糖素样肽-1（GLP-1）的降糖作用机制。方法40RsD雄性大鼠，随机分为正常组（N组）、模型组（M组）、二甲双胍组（MET组）、GLP-1组（GLP-1组），每组各10只。除N组外，其余大鼠高脂饲料喂养8周后，按30mg/kg腹腔注射链脲佐菌素（STZ）进行2型糖尿病造模。造模后，MET组、GLP-1组分别以二甲双胍及GLP-1治疗，N组和M组等量生理盐水皮下注射，治疗6N后，收集大鼠粪便，进行肠道群16SrDNA测序分析。结果治疗6N后，与N组比较，M组、MET组、GLP-1组大鼠空腹血糖均显著升高（P〈0．01）；与M组比较，MET组与GLP．1组空腹血糖均显著下降（P〈0．01），且两组差异无统计学意义（P〉0．05）。Alpha多样性上．observed_species、shanno、chao3个指数均为N组〉GLP-1组〉MET组〉M组，与N组比较，M组、MET组3指数差异均有显著统计学意义（P〈0．01）．GLP-1组仅chao指数差异有统计学意义（P〈0．05）。与N组比较，M组拟杆菌门比例显著下降（P〈0.01），变形门、厚壁门比例显著升高（P〈0．01）；与M组比较，GLP-1组拟杆菌门比例显著升高（P〈0．01），变形菌门比例显著下降（P〈0．01）。与N组比较，M组乳酸杆菌属、双歧杆菌属比例显著下降（P〈0．01），大肠杆菌属、链球菌属比例显著升高（P〈0．01）；与M组比较，GLP-1组乳酸杆菌属、双歧杆菌属比例显著升高（P〈0．01），大肠杆菌属、链球菌属比例显著下降（P〈0．01）。结论GLP-1可能通过增加T2DM大鼠肠道菌群物种多样性．同时提高乳杆菌、双歧杆菌等益生菌比例，从而起到调控血糖的作用。

Objective To explore the mechanism of hypoglycemic effect of GLP-1 on the regulation of intestinal flora. Methods 40 SD male rats were randomly divided into normal group, model group, metformin group and GLP-1 group, 10 rats in each group. In addition to the N group, the other rats were fed with high fat diet for 8 weeks and intraperitoneal injection of STZ according to the 30mg/kg for type 2 diabetes model. MET and GLP-1 group were treated respectively with metformin and GLP-1, N and M groups were subcutaneous injected with normal saline for 6 weeks, then collected of rat feces to intestinal flora 16SrDNA sequence. Results Compared with N group, the fasting blood glucose of M, MET and GLP- 1 group rats were significantly elevated （ P〈0.01 ） ; compared with M group, MET and GLP-1 group were significantly decreased （ P〈0.01 ） , and no significant difference between the two groups （ P〈0.01 ） .The 3 indexes of observed species,shanno,and cbao were N grouP〉GLP-1 grouP〉MET grouP〉M group. Compared with N group, the 3 indexes＇ difference of M group and MET group had statistical significance （ P〈0.01 ） , while only Chao index difference of GLP-1 group had statistical significance （P〈0.01） . Compared with the N group, the proportion of Bacteroidetes of M group was significantly decreased （P〈0.01） , and the proportion of Proteobacteria and Firmicutes were significantly increased （P〈0.01） .Compared with the M group, the proportion of Bacteroidetes of GLP-1 group was significantly increased （P〈0.01） , and the proportion of Proteobacteria was significantly decreased （P〈0.01） .Compared with N group, the proportion of Lactobacillus and Bifidobacterium of M group were significantly decreased （P〈0.01） , and the proportion of Escheriehia and Streptococcus were significantly increased （P〈0.01） .Compared with M group, the proportion of Lactobacillus and Bifidobacterium of GLP-1 group were significantly increased （P〈0.01） , and the proportion of Escherichia and Streptococcus were significantly decreased （ P〈0.01 ） . Conclusion GLP-1 may increase the species diversity of the intestinal flora of T2DM rats, and increase the proportion of probiotics such as Lactobacillus and Bifidobacteria, thus playing a role in regulating blood glucose.