益生菌联合低聚果糖对小鼠非酒精性脂肪肝的影响及机制探讨

Combined treatment with probiotics and fructooligosaccharides in a mouse model of nonalcoholic fatty liver disease and its possible mechanism

二维码有效期 120s

摘要目的探讨副干酪乳杆菌N1115联合低聚果糖对小鼠非酒精性脂肪肝病的影响及其可能机制.方法 50只雄性C57BL/6小鼠随机分为5组,分别给予正常饮食(ND)、高脂饮食(HFD)、高脂饮食+副干酪乳杆菌N1115(2.2×109 CFU/ml)(HFD+L)、高脂饮食+低聚果糖(4 g/kg)(HFD+FOS)、高脂饮食+副干酪乳杆菌N1115+低聚果糖(HFD+L+FOS),所有实验组小鼠连续干预16周.干预结束后,检测各组小鼠甘油三酯(TG)、胆固醇(TC)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)水平以及血清内毒素(LPS)、二胺氧化酶(DAO)水平;检测小肠黏膜紧密连接蛋白Claudin-1和Occludin的表达水平,并检测小肠p38、p-p38的表达.结果与高脂饮食组相比,副干酪乳杆菌N1115联合低聚果糖干预可显著降低非酒精性脂肪性肝病(non-alcoholic fatty liver disease, NAFLD)小鼠血清TC、TG、LDL、LPS、DAO水平,升高血清HDL水平,差异均有统计学意义(P<0.05).同时改善肝脏脂质沉积,增加肠道紧密连接蛋白Claudin-1和Occludin的表达,抑制肠道p38的激活,差异均有统计学意义 (P<0.05).结论副干酪乳杆菌N1115联合低聚果糖可能通过抑制肠道p38的激活,增加肠道紧密连接蛋白Claudin-1和Occludin的表达,增加肠黏膜屏障的完整性,从而起到改善NAFLD的作用.

abstractsObjective To investigate the effectiveness of Lactobacillus paracasei N1115 combined with fructooligosaccharides (FOS) in the treatment of nonalcoholic fatty liver disease(NAFLD) in a mouse model and to analyze the possible mechanism.Methods Fifty male C57BL/6 mice were randomly divided into five groups and respectively given normal diet (ND group), high-fat diet (HFD group), HFD containing Lactobacillus paracasei N1115 (HFD+L) (2.2×109 CFU/ml), HFD containing FOS (HFD+FOS) (4 g/kg per day) and HFD containing Lactobacillus paracasei N1115 and FOS for 16 consecutive weeks.Levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), lipopolysaccharide (LPS) and diamine oxidase (DAO) in serum samples from each group were measured.Expression of tight-junction proteins (Claudin-1 and Occludin), p38 and phosphorylated p38 (p-p38) in intestinal tissues were analyzed.Results Compared with the HFD group, the HFD+FOS+L group showed decreased levels of TC, TG, LDL, LPS and DAO in serum samples, but increased serum HDL level (P<0.05).Moreover, combined treatment with Lactobacillus paracasei N1115 and FOS alleviated liver lipid deposition, significantly increased the expression of Claudin-1 and Occludin in intestine and inhibited the phosphorylation of p38 (P<0.05).Conclusion Lactobacillus paracasei N1115 combined with FOS may increase the expression of Claudin-1 and Occludin through inhibiting the phosphorylation of intestinal p38, which is conducive to maintaining the intestinal mucosal barrier integrity and alleviating NAFLD.

作者姚芳芳 ^[1] 黄煌 ^[2] 白利梅 ^[2] 丁一芮 ^[2] 梅璐 ^[2] 刘思濛 ^[2] 郑鹏远 ^[2] 学术成果认领

作者单位 450052 郑州大学第五附属医院消化内科;450014 郑州大学第二附属医院临床营养科 ^[1] 450052,郑州大学第五附属医院消化内科 ^[2]

关键词 NAFLD 副干酪乳杆菌N1115 低聚果糖肠黏膜屏障 NAFLD Lactobacillus paracasei N1115 Fructooligosaccharides Intestinal mucosal barrier

主题词果糖(Fructose)小鼠(Mice)副干酪乳杆菌(Lactobacillus paracasei)脂肪肝, 酒精性(Fatty Liver, Alcoholic)肠黏膜(Intestinal Mucosa)

栏目名称 基础免疫学

DOI 10.3760/cma.j.issn.0254-5101.2017.07.009

发布时间 2017-08-28

基金项目

国家自然科学基金 国家科技部十二五课题 国家973计划前期研究专项 河南省科技厅重点攻关 郑州市创新型科技人才队伍建设工程基金 河南省科技创新杰出人才基金(134200510022).National Natural Science Foundation of China National Science & Technology Pillar Program during the 12th Five-Year Plan Period (2012BAI35B00) Special Prophase Research Project for National Program on Key Basic Research Project (973 Program) Key Technologies R & D Program of Henan Province of China Zhengzhou Municipal Fund for Fostering Innovative Talents in Science and Technology Henan Provincial Foundation for Outstanding Innovative Talents in Science and Technology