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基于肠道菌群和代谢组学的芜菁多糖改善小鼠酒精性肝损伤机制研究
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| 篇名： | 基于肠道菌群和代谢组学的芜菁多糖改善小鼠酒精性肝损伤机制研究 |
| TITLE： | Study on the mechanism of Brassica rapa polysaccharide in improving alcoholic liver injury of mice based on intestinal microbiota and metabolomics |
| 摘要： | 目的 研究芜菁多糖（BRP）对酒精性肝损伤小鼠肝组织中Toll样受体4（TLR4）/髓样分化因子88（MyD88）/核因子κB（NF-κB）、AMP活化蛋白激酶（AMPK）/固醇调节元件结合蛋白1c（SREBP-1c）信号通路，肠道菌群和肝脏代谢的影响，初步阐明其改善酒精性肝损伤的机制。方法将72只小鼠随机分为空白组（生理盐水）、模型组（生理盐水）、联苯双酯组（阳性对照，300mg/kg）和BRP低、中、高剂量组（75、150、300mg/kg），每天灌胃给药1次，连续9d。末次给药后，除空白组外的其余各组小鼠均灌胃白酒建立酒精性肝损伤模型。检测小鼠血清中丙氨酸转氨酶、天冬氨酸转氨酶以及肝组织中总胆固醇、甘油三酯、低密度脂蛋白胆固醇、白细胞介素6、白细胞介素1β、肿瘤坏死因子α、脂多糖水平和TLR4、MyD88、NF-κBp65、磷酸化NF-κBp65（p-NF-κB65）、AMPK、磷酸化AMPK（p-AMPK）、SREBP-1c的蛋白表达水平；观察肝组织和结肠组织病理形态学变化。利用16SrRNA技术检测小鼠肠道菌群的变化，利用代谢组学技术检测肝脏代谢物的变化。结果与模型组比较，BRP各剂量组小鼠上述生化指标和肝组织中TLR4、MyD88、p-NF-κBp65、SREBP-1c的蛋白表达水平均显著降低（P＜0.05或P＜0.01），p-AMPK的蛋白表达水平均显著升高（P＜0.05或P＜0.01）；肝组织和结肠组织病理损伤均显著改善。中剂量BRP可在一定程度上升高小鼠肠道内容物中艾克曼菌属、norank_f_Muribaculaceae、Lachnospiraceae_NK4A136_group等的相对丰度，降低乳杆菌属的相对丰度和大肠埃希菌属-志贺菌属的相对丰度；代谢组学共鉴定出尿黑酸、肉豆蔻酰溶血磷脂酰胆碱等9个差异代谢物，涉及酪氨酸代谢等通路。结论BRP可回调有益菌群的相对丰度、降低有害菌群的相对丰度，改善肠道菌群结构，减少促炎介质脂多糖进入肝组织，影响肝脏中酪氨酸代谢等代谢通路和TLR4/MyD88/NF-κB、AMPK/SREBP-1c信号通路的表达，最终改善酒精性肝损伤。 |
| ABSTRACT： | OBJECTIVE To investigate the effects of Brassica rapa polysaccharide （BRP） on the Toll-like receptor 4 （TLR4）/ myeloid differentiation factor 88 （MyD88）/nuclear factor-κB （NF-κB）， AMP-activated protein kinase （AMPK）/sterol regulatory element-binding protein-1c （SREBP-1c） pathways， intestinal microbiota and liver metabolism of mice with alcoholic liver injury， and preliminarily elucidate its mechanism for improving alcoholic liver injury. METHODS Seventy-two mice were randomly divided into blank group （normal saline）， model group （normal saline）， bifendate group （positive control， 300 mg/kg） and BRP low-， medium- and high-dose groups （75， 150 and 300 mg/kg）. They were given relevant medicine intragastrically， once a day， for consecutive 9 d. After the last administration， mice in all groups except the blank group were gavaged with white liquor to establish an alcoholic liver injury model. The levels of alanine aminotransferase and aspartate aminotransferase in serum， total cholesterol， triglycerides， low-density lipoprotein cholesterol， interleukin-6， interleukin-1β， tumor necrosis factor- α and lipopolysaccharide， as well as protein expressions of TLR4， MyD88， NF-κB p65， phosphorylated NF-κB p65 （p-NF-κB p65）， AMPK， phosphorylated AMPK （p-AMPK）， and SREBP-1c were all detected； pathological morphological changes of liver tissue and colon were observed. 16S rRNA was used to detect the changes of intestinal microbiota in mice， and metabolomics 2022B02058） technology was used to detect the changes of liver metabolites. RESULTS Compared with model group， the above biochemical indicators and the protein expressions of TLR4， MyD88， p-NF-κB p65， and SREBP-1c in liver tissues were all significantly decreased （P＜0.05 or P＜0.01）， while the protein expression of p-AMPK was significantly increased （P＜0.05 or P＜0.01）. Pathological damage to liver and colon tissues was significantly improved. Medium dose of BRP could increase the relative abundance of Akkermansia， norank_f_Muribaculaceae and Lachnospiraceae_NK4A136_group in the intestinal contents of mice to a certain extent， and decrease the relative abundance of Lactobacillus and Escherichia-Shigella. A total of 9 differential metabolites were identified by metabolomics， including homogentisic acid， myristyl lysophosphatidylcholine， which were involved in pathways such as tyrosine metabolism. CONCLUSIONS BRP can regulate the relative abundance of beneficial flora， reduce the relative abundance of harmful flora， improve the structure of intestinal colonies， reduce the entry of pro-inflammatory mediator lipopolysaccharides into liver tissue， affect metabolic pathways such as tyrosine metabolism and the expression of TLR4/MyD88/NF- κB and AMPK/SREBP-1c signaling pathways in the liver， and ultimately improve alcoholic liver injury. |
| 期刊： | 2025年第36卷第16期 |
| 作者： | 马鑫莹；许瑞娜；李勺玄；叶瑞银；马越兴；叶耀辉 |
| AUTHORS： | MA Xinying，XU Ruina，LI Shaoxuan，YE Ruiyin，MA Yuexing，YE Yaohui |
| 关键字： | 酒精性肝损伤；芜菁多糖；肠道菌群；代谢组学 |
| KEYWORDS： | alcoholic liver injury； Brassica rapa polysaccharides； intestinal microbiota； metabolomics |
| 阅读数： | 4 次 |
| 本月下载数： | 0 次 |
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