【摘要】 目的:研究大鼠体内不同肠道菌群状态的改变对其非酒精性脂肪性肝病(NAFLD)发生发展的影响,为菌群失调动物模型的造模提供新方法,也为NAFLD在肠道菌群方面的防治提供可靠的理论依据。方法:50只雄性SD大鼠随机分为5组,其中3组使用高剂量抗生素头孢曲松溶液灌胃,建立肠道菌群失调模型后分为C组、D组和E组,C组饲以普通饲料、D组为高脂饲料、E组高脂饲料喂养同时使用益生菌灌胃,此3组在喂养期间,继续饮用低浓度头孢曲松溶液以保持肠道菌群失调状态;另2组生理盐水灌胃,作为肠道菌群正常模型,分为A组和B组,分别饲以普通饲料、高脂饲料。12周后收集标本,检测血脂、肝功能指标,行病理组织学检查明确肝组织病变程度,采用ELISA法测定血清脂联素水平。结果:同为普通饲料喂养的A组肝脏正常,而C组大鼠则出现少量的脂肪空泡。高脂饲料喂养的大鼠均造模NAFLD成功,B组肝脏为单纯性脂肪肝改变,抗生素作用的D组出现脂肪性肝炎(NASH),而益生菌干预的E组肝脏虽有炎症改变,但病变程度较D组大为改善。除D组血清脂联素水平明显降低外(P<0.05),其余各组大鼠均与A组无明显差异(P>0.05)。结论:肠道菌群的变化与NAFLD的发展存在明显的相关性,肠道菌群越紊乱,NAFLD病变程度越严重。微生态制剂可调节肠道菌群构成、改善NAFLD病变;血清脂联素浓度可能受血脂和肠道菌群双重影响,对肝脏起保护性作用,当NAFLD病变进展到NASH阶段时出现明显降低。更多还原

【Abstract】 Objective: To investigate the impact of dysregulated intestinal flora on occurrence and development of non-alcoholic fatty liver disease( NAFLD),so as to provide a new method for animal modeling of dysregulated intestinal flora,and to provide a reliable theoretical basis for the prevention and treatment of dysregulated intestinal flora in NAFLD. Methods: Fifty male SD rats were randomly divided into five groups.Three groups of rats received garvage of high-dose oral ceftriaxone for modeling of dysregulated intestinal flora,and were then assigned as groups C,D and E. The group C was fed on usual diet,D on high-fat diet,and group E on high-fat diet plus oral probiotics. During the feeding,these three groups were kept on low-dose oral ceftriaxone to maintain a status of dysregulated intestinal flora. The other two groups,assigned as groups A and B,received garvage of normal saline for modeling of normal intestinal flora,and were fed on usual diet and highfat diet,respectively. After 12 weeks,rat liver tissue specimens were collected. Serum lipid level and liver functions were measured. Histopathological study was performed to examine the severity liver lesions. ELISA assay was used to determine the serum adiponectin level. Results: For rats on usual diet,the liver tissues of group A appeared normal,whereas those of group C presented a few fatty vacuoles. Rats fed on high-fat diet were successfully modeled for NAFLD. the liver tissues of group B presented simple signs of liver steatosis,whereas those of the ceftriaxone-treated group D showed signs of non-alcoholic steatohepatitis( NASH). With probiotics intervention,the liver tissues of group E presented inflammatory changes,but the severity was greatly improved compared with group D. Except for group E with significantly lower adiponectin level( P < 0.05),there was no significant difference in serum adiponectin level between group A and the other groups of rats( P > 0. 05).Conclusion: Alteration in intestinal flora is significantly related to development of NAFLD,with greater severity of dysregualted intestinal flora,more serious NAFLD. Probiotics may modify the composition of intestinal flora,and improve the NAFLD lesions. The level of serum adiponectin which appears to be hepatoprotective,may be affected both by serum lipids and intestinal flora,and may become significantly lowered when NAFLD evolves into NASH.更多还原