益生菌调节肠道微生物群/Nrf2/HO-1信号通路对高脂喂养大鼠非酒精性脂肪肝的影响  

Probiotics reduce nonalcoholic fatty liver disease in rats fed with high-fat diet through the intestinal microbiota/Nrf2/HO-1 signaling pathway

作　　者：李文娟 潘美民 刘阳珍 何娟 蔡春琳 LI Wenjuan;PAN Meimin;LIU Yangzhen;HE Juan;CAI Chunlin(Infection Department of Changsh First Hospital,Changsha 410005,China)

机构地区：[1]长沙市第一医院感染科,湖南长沙410005

出　　处：《中国病原生物学杂志》2024年第1期42-46,共5页Journal of Pathogen Biology

基　　金：湖南省卫生健康委科研计划项目(No.202203103003)。

摘　　要：目的 探究益生菌对非酒精性脂肪肝(nonalcoholic fatty liver disease, NAFLD)大鼠肠道微生物群的调节作用,以及益生菌调节大鼠Nrf2/HO-1信号通路的可能机制。方法 建立喂食高脂饮食(high-fat diet, HFD)14周的NAFLD大鼠模型,并对其进行不同干预(312 mg/(kg·d)益生菌)或(10 mg/(kg·d)阿托伐他汀),采用相应的试剂盒测定各组大鼠血清脂质和总胆汁酸(total bile acids, TBA);通过苏木精-伊红染色检测大鼠肝脂肪变性和脂质积聚情况;采用Western blot检测大鼠肝脏中Nrf2和HO-1蛋白水平;采用RT-PCR检测16S rDNA,分析大鼠肠道微生物群的变化。结果 苏木精-伊红染色染色显示,对照组大鼠肝小叶结构清晰完整,无脂质浸润。HFD组有明显的脂肪变性、脂肪泡、肝索结构紊乱和炎症细胞浸润。HFD-P和HFD-A组肝脏脂肪变性和炎症细胞浸润显著减少。NAS的结果显示,HFD组的肝脏炎症较NC组严重;HFD-P组和HFD-A组治疗后肝脏炎症显著改善。与HFD组相比,益生菌和阿托伐他汀显著降低了血脂和TBA水平。益生菌显著增加肝脏中Nrf2和HO-1蛋白质的表达。但阿托伐他汀组无明显变化。益生菌和阿托伐他汀可以上调NAFLD模型大鼠肠道微生物群的多样性,并下调致病菌的丰度。结论 益生菌通过调节肠道微生物群/Nrf2/HO-1信号通路减轻HFD大鼠的NAFLD,这些结果提示益生菌治疗可能是改善非酒精性脂肪肝病的有效策略。Objective To explore the regulatory effect of probiotics on intestinal microbiota in rats with nonalcoholic fatty liver disease(NAFLD),and to explore the possible mechanism of probiotics regulating Nrf2/HO-1 signaling pathway in rats.Methods A NAFLD rat model was established by feeding high-fat diet(HFD)for 14 weeks,and different interventions(312 mg/(kg·d)probiotics or 10 mg/(kg·d)atorvastatin)were performed.Serum lipids and total bile acids(TBA)were measured by corresponding kits.Hepatic steatosis and lipid accumulation in rats were detected by hematoxylin-eosin staining.The protein levels of Nrf2 and HO-1 in rat liver were detected by Western blot.RT-PCR was used to detect 16 S rDNA,and the changes of intestinal microflora in rats were analyzed.Results Hematoxylin-eosin staining showed that the structure of hepatic lobules in the control group was clear and complete without lipid infiltration.The HFD group had obvious steatosis,fat bubbles,hepatic cord structure disorder and inflammatory cell infiltration.Hepatic steatosis and inflammatory cell infiltration were significantly reduced in HFD-P and HFD-A groups.The results of NAS showed that the liver inflammation in the HFD group was more serious than that in the NC group.Liver inflammation was significantly improved in HFD-P group and HFD-A group after treatment.Compared with the HFD group,probiotics and atorvastatin significantly reduced blood lipid and TBA levels.Probiotics significantly increased the expression of Nrf2 and HO-1 proteins in the liver.However,there was no significant change in the atorvastatin group.Probiotics and atorvastatin can up-regulate the diversity of intestinal microflora in NAFLD model rats and down-regulate the abundance of pathogenic bacteria.Conclusion Probiotics alleviate NAFLD in HFD rats by regulating the gut microbiota/Nrf2/HO-1 signaling pathway.These results suggest that probiotic treatment may be an effective strategy to improve non-alcoholic fatty liver disease.

关 键 词：益生菌 肠道微生物群 Nrf2/HO-1信号通路 非酒精性脂肪肝 

分 类 号：R575.5[医药卫生—消化系统]