Objective: To investigate the effects of Lactobacillus paracasei N1115 combined with fructooligosaccharides (FOS) on non-alcoholic fatty liver disease (NAFLD) in mice and its possible mechanism. Methods: A total of 50 male C57 mice were randomly and equally divided into five experimental groups. Group 1 received a normal diet (ND). Other four groups received a high-fat diet (HFD) to establish NAFLD models. In addition to HFD, group 3 received Lactobacillus paracasei N1115 (2.2×10(9) CFU/mL), group 4 received FOS (4 g/kg per day), and group 5 received Lactobacillus paracasei N1115 (2.2×10(9) CFU/mL) and FOS (4 g/kg per day). All groups received continuous intervention for 16 weeks. The following indices were measured for all groups after intervention: general condition, the levels of fasting blood glucose, insulin, and lipopolysaccharide (LPS), and the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and interferon (IFN)-γ in the serum and liver. The mRNA levels of Toll-like receptor (TLR)4, nuclear factor (NF)-κb, insulin receptor (InsR), and insulin receptor substrate (IRS)-1 were measured by real-time RT-PCR. The data were subjected to one-way analysis of variance and comparison between groups was made by Bonferroni method. Results: Compared with group 2, groups 3, 4, and 5 had significantly lower body weight, Lee's index, liver index, and the levels of blood glucose and insulin resistance (P < 0.05). The serum level of LPS in group 2 was significantly higher than that in the other experimental groups (group 1: 8.80 ± 0.85 U/L, group 3: 12.31 ± 1.01 U/L, group 4: 12.27 ± 0.98 U/L, and group 5: 10.17 ± 0.79 U/L vs group 2: 15.45 ± 1.14 U/L, F = 55.117, P < 0.001). The levels of TNF-α, IL-1β, IL-6, and IFN-γ in the serum and liver in group 2 were also significantly higher than those in the other groups (P < 0.05). Group 2 had significantly higher mRNA levels of TLR4 and NF-κb in the liver than the other groups (F = 82.933, P < 0.001; F = 149.033, P < 0.001); however, it had significantly lower mRNA levels of InsR and IRS-1 in the liver than the other groups (F = 33.347, P < 0.001; F = 70.225, P < 0.001). Conclusion: Lactobacillus paracasei N1115 combined with FOS can reduce the level of LPS in the blood circulation, inhibit activation of the LPS/TLR4 signaling pathway, and reduce the release of inflammatory factor and the body's insulin resistance, so it can relieve NAFLD.
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性肝病的影响及其可能机制。 方法： 50只雄性C57小鼠随机分为5组，分别给予正常饮食、高脂饮食、高脂饮食+副干酪乳杆菌N1115（2.2×10(9) CFU/ml）、高脂饮食+低聚果糖（4 g/kg）、高脂饮食+副干酪乳杆菌N1115 +低聚果糖，所有实验组小鼠连续干预16周。干预结束后，检测各组小鼠空腹血糖、胰岛素、脂多糖（LPS）以及血清和肝脏的肿瘤坏死因子α、白细胞介素（IL）-1β、IL-6和干扰素γ水平；RT-PCR检测小鼠肝脏Toll样受体（TLR）4、核因子-κB、胰岛素受体、胰岛素受体底物-1 mRNA表达水平。对数据采用单因素方差分析，两两比较用Bonferroni法。 结果： 与高脂饮食组相比，副干酪乳杆菌N1115、低聚果糖干预明显降低高脂饮食小鼠的体质量、Lee's指数、肝指数以及血糖、胰岛素抵抗水平，正常饮食组血清LPS水平为（8.80±0.85）U/L，副干酪乳杆菌N1115、低聚果糖及二者联合干预组血清LPS水平分别为（12.31±1.01）U/L、（12.27±0.98）U/L、（10.17±0.79）U/L，而高脂饮食组为（15.45±1.14）U/L，明显高于其他各实验组（F = 55.117，P < 0.01）；各干预组血清和肝脏中肿瘤坏死因子α、IL-1β、IL-6、干扰素γ水平与高脂饮食组相比，亦明显降低（P < 0.05）；同时下调了肝脏TLR4、核因子-κB mRNA的表达（F值分别为82.933,149.033，P值均< 0.01），并上调肝脏胰岛素受体、胰岛素受体底物-1 mRNA的表达(F值分别为33.347，70.225，P值均< 0.01)。 结论： 副干酪乳杆菌N1115联合低聚果糖可通过减少循环LPS的水平，抑制LPS/TLR4信号通路的激活，减少炎症因子的释放，减轻机体胰岛素抵抗，从而起到改善非酒精性脂肪性肝病的作用。.
Keywords: Fatty liver; Fructooligosaccharides; Inflammation; Lactobacillus paracasei N1115.