乳酸片球菌AS185调节高脂高糖饮食诱导的代谢综合征

目的：研究乳酸片球菌（Pediococcus acidilactici）AS185对代谢综合征小鼠的调节作用，并探讨其作用机制。方法：高脂高糖饮食诱导小鼠代谢综合征造模（6 周），灌胃乳酸片球菌AS185，每天1 次，连续8 周，通过测量体质量、血糖浓度、血脂和血清炎症因子水平并进行Western blot检测，评价乳酸片球菌AS185菌株改善代谢综合征的作用和机制。结果：灌胃乳酸片球菌AS185可降低高脂高糖饮食诱导的代谢综合征小鼠血清中总胆固醇、甘油三酯、低密度脂蛋白胆固醇、肿瘤坏死因子-α、白细胞介素-1β、白细胞介素-6、胰岛素、空腹血糖、游离脂肪酸、C-反应蛋白和脂多糖水平。Western blot分析结果表明，乳酸片球菌AS185抑制了高脂高糖诱导的核因子κB蛋白的活化、Toll样受体4（Toll-like receptor 4，TLR4）及髓样分化因子（myeloid differentiation factor 88，MyD88）蛋白的表达，抑制炎症通路和炎症因子的表达。乳酸片球菌AS185通过激活肝组织中肝激酶B1（liver kinase B1，LKB1）和腺苷酸活化蛋白激酶（adenylate activated protein kinase，AMPK）的表达，提高磷酸化AMPK和磷酸化乙酰辅酶A羧化酶蛋白表达，并抑制固醇调节元件结合蛋白1c蛋白的表达，调节脂类代谢通路。结论：乳酸片球菌AS185通过激活TLR4-MyD88-NF-κB通路，降低小鼠血清中的炎症因子的水平，并通过激活LKB1-AMPK信号通路，改善代谢综合征小鼠的血脂紊乱，调节高脂高糖饮食导致的代谢综合征。

Pediococcus acidilactici AS185 Improves Metabolic Syndrome Induced by a High-Fat and High-Fructose Diet

Objective:To study the regulatory effect and underlying mechanism of Pediococcus acidilactici AS185 on metabolic syndrome(MS)in mice.Methods:ICR mice were given a high-fat and high-fructose diet once a day for 6 consecutive weeks to establish an MS model,and AS185 was administered by gavage to the animals once a day from week 7 to 14.The body mass,blood glucose,blood lipid and serum inflammatory factors were determined and Western blot was performed to analyze the expression of relevant proteins.Results:The administration of P.acidilactici AS185 could reduce the serum levels of total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),tumor necrosis factor(TNF)-α,interleukin(IL)-1β,IL-6,insulin(INS),fasting blood glucose(FBG),free fatty acid(FFA),C-reactive protein(CRP)and lipopolysaccharide(LPS)in the mouse model.Western blot analysis showed that P.acidilactici AS185 inhibited the activation of nuclear factor(NF)-κB,and the expression of Toll-like receptor 4(TLR4)and myeloid differentiation factor 88(MyD88),suppressed inflammatory signaling pathways and the expression of inflammatory factors in the high-fat and high-fructose diet-fed mice.Moreover,it activated liver kinase B1(LKB1)and the expression of adenylate activated protein kinase(AMPK),thereby enhancing the expression of phosphorylated AMPK(p-AMPK)and phosphorylated acetyl-CoA carboxylase(p-ACC),down-regulating the expression of sterol regulatory element-binding protein-1c(SREBP-1c)and finally regulating the lipid metabolism pathway.Conclusion:P.acidilactici AS185 can improve high-fat and high-fructose diet-induced metabolic syndrome in mice by activating the TLR4-MyD88-NF-κB pathway to regulate inflammatory factor levels,and activating the LKB1-AMPK signaling pathway to improve blood lipid disorders.