| 摘要: |
| 目的：本研究旨在评估益生菌对高脂饮食(High-fat diet,HFD)诱导的非酒精性脂肪性肝病(Non-alcoholic fatty liver disease,NAFLD)的保护作用,并进一步探索基于肠道菌群调控的可能机制。方法：通过HFD诱导建立大鼠NAFLD模型,并随机分为六组：对照组、HFD组、DM9054组(鼠李糖乳杆菌)、86066组(植物乳杆菌)、N1115组(副干酪乳杆菌)组和复合益生菌组。各益生菌的浓度均为1×101? CFU/mL,通过灌胃给药,每天一次,持续150天。对照组和HFD组灌胃等量生理盐水。实验期间,记录大鼠体重、Lee’s指数、肝指数及生化指标。随后,利用油红O染色和苏木精-伊红(Hematoxylin and eosin,H E)染色观察肝组织病理变化,并通过qPCR和Western blot检测Toll样受体4(Toll-like receptor,TLR4)、髓样分化因子88(Myeloid differentiation factor 88,MyD88)、核因子κB(Nuclear factor kappa B,NF-κB)的mRNA和蛋白表达水平。最后,采用16S rRNA测序分析肠道菌群的组成和结构变化。结果：与HFD组相比,单独或复合益生菌组的大鼠,其最终体重和肝指数显著降低,Lee’s指数下降,肝脏损伤显著改善,炎症因子水平显著降低,TLR4、MyD88、NF-κB p65 mRNA表达和蛋白表达下调,其中复合益生菌组的效果最明显。此外,复合益生菌处理后,肠道菌群中g_Shigella、f_Prevotellaceae、g_Prevotella、f_Verrucomicrobiaceae、o_Verrucomicrobiales、p_Verrucomicrobia、c_Verrucomicrobiae和g_Akkermansia等菌的相对丰度显著增加。结论：益生菌可降低NAFLD大鼠的炎症水平,并改善肠道菌群组成,其调控机制可能与TRL4/NF-κB通路相关。 |
| 关键词: 非酒精性脂肪性肝病 益生菌 肠道菌群 TLR4/NF-κB通路 |
| DOI： |
| 分类号: |
| 基金项目:金华市科技计划项目 |
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| Study on the Effect and Mechanism of Probiotic Complex on Nonalcoholic Fatty Liver Disease |
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SHAO Honghua, ZHU Liang, WANG Qunxing
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Jinhua Central Hospital
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| Abstract: |
| OBJECTIVE: The aim of this study was to evaluate the protective effects of probiotics against high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) and to further explore possible mechanisms based on intestinal flora. METHODS: A rat NAFLD model was established by high-fat diet (HFD) induction and randomly divided into six groups: control group, HFD group, DM9054 group (Lactobacillus rhamnosus), 86066 group (Lactobacillus plantarum), N1115 group (Lactobacillus paracasei), and the combined probiotics group. The concentration of each probiotic was 1 × 101? CFU/mL, administered by gavage once daily for 150 days. The control and HFD groups were gavaged with equal amounts of saline. During the experimental period, body weight, Lee's index, liver index and biochemical indices of rats were recorded. Subsequently, oil red O staining and Hematoxylin and eosin (H&E) staining were used to observe the pathological changes of liver tissue, and the mRNA and protein expression levels of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and nuclear factor kappa B (NF-κB) were detected by qPCR and Western blot. Finally, 16S rRNA sequencing was used to analyze the compositional and structural changes of the intestinal flora. RESULTS: Compared with the HFD group, rats in the probiotic alone or in combination groups had significantly lower final body weights and liver indices, lower Lee's index, improved liver injury, significantly lower levels of inflammatory factors, and down-regulated expression of TLR4, MyD88, NF-κB p65 mRNA expression and protein expression. The effect was most pronounced in the probiotic complex group. In addition, the relative abundance of g_Shigella、f_Prevotellaceae、g_Prevotella、f_Verrucomicrobiaceae、o_Verrucomicrobiales、p_Verrucomicrobia、c_Verrucomicrobiae and g_Akkermansiain the intestinal flora was significantly increased by the complex probiotic treatment. CONCLUSION: Probiotics reduced inflammation levels and improved the composition of intestinal flora in NAFLD rats, and their regulatory mechanisms may be related to the TRL4/NF-κB pathway. |
| Key words: NAFLD Probiotics Intestinal flora TRL4/NF-κB pathway |