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目的探索阿托伐他汀作用于2型糖尿病小鼠对其肠道菌群的影响。方法 20只小鼠随机按照1∶3分成对照组和模型组,采用高糖高脂喂食及链脲佐菌素腹腔注射的15只成模模型组小鼠随机分为模型组、二甲双胍组、阿托伐他汀组,每组5只,二甲双胍组和阿托伐他汀组各分别给予20 mg/kg和4 mg/kg 20 d灌胃干预。干预后收集小鼠血清及新鲜粪便,血清检测随机血糖、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C),C反应蛋白(CRP)、内毒素(LPS)以及应用实时荧光定量核酸扩增检测系统(q PCR)绝对定量检测肠道菌群(肠杆菌、乳杆菌、双歧杆菌、拟杆菌、肠球菌和总菌)数量。结果对照组与模型组的血糖、TC、TG、HDL-C、LDL-C、体重、CRP、LPS比较差异均具有统计学意义(P<0.05);对照组与二甲双胍组的TC、TG、HDL-C、LDL-C、体重、CRP、LPS比较差异均具有统计学意义(P<0.05);对照组与阿托伐他汀组的血糖、TC、TG、HDL-C、LDL-C、体重、CRP比较差异均具有统计学意义(P<0.05)。二甲双胍组与阿托伐他汀组的血糖、TC、TG、HDL-C、LDL-C、LPS比较差异均具有统计学意义(P<0.05)。各组肠道总菌比较差异无统计学意义(P>0.05),表明各组肠道菌群总量一致。与对照组比较,模型组2型糖尿病肠道菌群中肠杆菌、肠球菌增加,乳杆菌、双歧杆菌和拟杆菌减少,且干预后具体菌属改变主要表现为:二甲双胍组和阿托伐他汀组肠杆菌和肠球菌均减少,乳杆菌、双歧杆菌和拟杆菌增加(P<0.05);而二甲双胍组较阿托伐他汀组更加能提高双歧杆菌和拟杆菌的数量(P<0.05),阿托伐他汀组较二甲双胍组更加能减少肠杆菌、肠球菌和提高乳杆菌的数量(P<0.05)。结论阿托伐他汀可以通过减少肠杆菌和肠球菌致病菌和增加乳杆菌益生菌以及减少其代谢产物LPS来调节2型糖尿病肠道菌群,其可能是他汀降脂药作用于2型糖尿病的机制之一。
Objective To explore the effect of atorvastatin on intestinal flora in type 2 diabetic mice. Methods Twenty mice were randomly divided into control group and model group according to 1: 3. 15 mice in model group were randomly divided into model group, metformin group, high fat and fat diet group and intraperitoneal injection of streptozotocin Atorvastatin group, each group of 5, metformin group and atorvastatin group were given 20 mg / kg and 4 mg / kg 20 d gavage intervention. Serum and fresh faeces were collected after intervention. Serum levels of blood glucose, TC, TG, LDL-C, HDL-C, C reactive protein (CRP), endotoxin (LPS), and absolute quantitative detection of intestinal flora (Enterobacter, Lactobacillus, Bifidobacterium, Bacteroides, Enterococcus and Total bacteria) quantity. Results The levels of TC, TG, HDL-C, LDL-C, body weight, CRP and LPS in the control group and the model group were significantly different (P <0.05) C, LDL-C, body weight, CRP and LPS in the control group and atorvastatin group were significantly different (P <0.05) CRP differences were statistically significant (P <0.05). Metformin group and atorvastatin group, blood glucose, TC, TG, HDL-C, LDL-C, LPS differences were statistically significant (P <0.05). The total intestinal bacteria in each group was no significant difference (P> 0.05), indicating that the total intestinal flora in each group the same. Compared with the control group, the enterobacteriaceae and enterococci in the model group were increased in the gut microbiota, and the number of Lactobacillus, Bifidobacterium and Bacteroides were decreased in the model group, and the changes in the specific bacteria were mainly metformin and atorvastatin Enterobacteriaceae and enterococci in the statin group were decreased, Lactobacillus, Bifidobacterium and Bacteroides increased (P <0.05), while those in the metformin group were more able to increase the number of Bifidobacterium and Bacteroides (P <0.05 ), Atorvastatin group more than the metformin group can reduce Enterobacter, enterococci and increase the number of Lactobacillus (P <0.05). Conclusions Atorvastatin can regulate intestinal flora of type 2 diabetes by reducing pathogenic bacteria of enterobacter and enterococci and increasing Lactobacillus probiotics as well as its metabolite LPS, which may be the effect of statin lipid-lowering drugs on type 2 diabetes mellitus One of the mechanisms.