高脂饮食对NAFLD模型大鼠肠道菌群及血清LPS水平的影响

摘要

Objective To observe the changes of intestinal flora and serum lipopolysaccharide(LPS) levels in rats with nonalcoholic fatty liver disease (NAFLD) induced by feeding with fat diet,and to explore the changes of intestinal flora and the role of endotoxin in the pathogenesis of NAFLD.Methods Male SD rats were randomly divided into control group and high fat group.The control group was fed with normal diet,high fat group was fed with high fat diet.The rats were sacrificed at the end of 16th week.Biochemical indexes were measured by automatic biochemical analyzer,the pathological changes of liver in two groups were observed by electron microscope,the changes of serum LPS,IL-1 β,IL-18 levels detected by ELISA,and the expression of Escherichia coli(E.cali) and Lactobacillus in fecal were detected by real-time fluorescence quantitative PCR method.Results The levels of serum ALT,AST,TC,TG and VLDL in high fat were significantly higher than those of control group.The serum level of LPS,IL-1 β,IL-18 were significantly increased in high fat group,and the difference was statistically significant(P ＜ 0.05);Compared with the control group,E.coli in high fat group was significantly increased,while the Lactobacillus was significantly decreased (P ＜ 0.05).There was a correlation between the level of serum endotoxin and the amount of E.coli.Conclusion There is change of intestinal flora and endotoxin in NAFLD model rats induced by high fat diet.Irrational dietary structure and changes in fecal flora play important roles in the pathogenesis of NAFLD.%目的 观察高脂饮食诱导的非酒精性脂肪肝病(NAFLD)模型大鼠肠道菌群及血清内毒素(LPS)水平的变化,探讨肠道菌群改变及LPS血症在NAFLD发病过程中的作用.方法 雄性SD大鼠12只随机分为对照组和高脂组,对照组以普通饮食饲养,高脂组给予高脂饲料喂养,于实验第16周末处死大鼠,采用全自动生化分析仪测定血清生化指标,电镜观察两组大鼠肝脏病理改变,ELISA法检测血清LPS、白介素(IL)-1β、IL-18水平的变化,通过实时荧光定量PCR法检测粪便大肠杆菌和乳酸杆菌的表达水平.结果 高脂组大鼠血清谷丙转氨酶、谷草转氨酶、三酰甘油、总胆固醇、极低密度脂蛋白水平较对照组明显升高,高密度脂蛋白水平明显降低,差异均有统计学意义(P＜0.05);与对照组相比,高脂组大鼠血清LPS、IL-1β、IL-18水平明显升高,差异均有统计学意义(P＜0.05).与对照组相比,高脂组大鼠的的大肠杆菌显著升高,而乳酸杆菌明显减少,差异有统计学意义(P＜0.05).血清LPS水平与大肠杆菌量存在相关性.结论 高脂饮食诱导的NAFLD模型大鼠存在LPS血症和肠道菌群的改变,不合理的饮食结构及粪便菌群的改变在NAFLD的发病过程中起着重要的作用.