基于TLR4/NF-κB信号通路探究涤浊汤对高尿酸血症大鼠肠道菌群紊乱的调节作用  

Regulatory effect of Dizhuo decoction on intestinal dysbiosis in hyperuricemic rats based on TLR4/NF-κB signaling pathway

作　　者：王菲[1] 辛凯[1] 陈丽[1] 李珊珊[1] 李金凤 WANG Fei;XIN Kai;CHEN Li;LI Shanshan;LI Jinfeng(Laboratory Department of the Third Affiliated Hospital of He′nan University of Traditional Chinese Medicine,Nanyang,He′nan 450000,China;不详)

机构地区：[1]河南中医药大学第三附属医院检验科,河南南阳450000

出　　处：《中国微生态学杂志》2024年第1期10-17,28,共9页Chinese Journal of Microecology

基　　金：河南省中医药科学研究专项课题(2023ZY2114)。

摘　　要：目的探究TLR4/NF-κB信号通路能否成为涤浊汤调节高尿酸血症大鼠肠道菌群紊乱的机制。方法将70只SPF级雄性SD大鼠随机分为NC组、HUA组、DZTL组、DZTM组、DZTH组、阳性对照组和DZTH+LPS组,每组10只。检测大鼠血清中尿酸(SUA)、肌酐(Cr)、尿素氮(BUN)、黄嘌呤氧化酶(XOD)和内毒素(LPS)水平。HE染色观察肾组织病理学变化;16S rDNA测序检测肠道菌群alpha多样性与肠道菌群群落结构;蛋白质印迹法检测肾组织中TLR4和p-NF-κB p65蛋白表达。结果与NC组相比,HUA组大鼠血清中SUA、Cr、BUN、XOD及LPS水平均显著升高(均P<0.05);与HUA组相比,DZTL组、DZTM组、DZTH组和阳性对照组大鼠血清中SUA、Cr、BUN、XOD、LPS水平以及Shannon指数、Sobs指数、Chao1指数、Ace指数均显著降低,DZTH组和阳性对照组变化最显著(均P<0.05);与DZTH组相比,DZTH+LPS组大鼠血清中SUA、Cr、BUN、XOD、LPS水平以及Shannon指数、Sobs指数、Chao1指数、Ace指数均显著升高(均P<0.05)。与NC组相比,HUA组厚壁菌门、放线菌门、梭状芽胞杆菌属、瘤胃菌属、乳杆菌属、颤螺菌属和双歧杆菌属相对丰度均显著降低,拟杆菌门、变形菌门、TM7菌门、拟杆菌属、产芽胞菌属和TM-3菌属相对丰度均显著升高(均P<0.05);与HUA组相比,DZTL组、DZTM组、DZTH组和阳性对照组厚壁菌门、放线菌门、梭状芽胞杆菌属、瘤胃菌属、乳杆菌属、颤螺菌属和双歧杆菌属相对丰度均显著升高,拟杆菌门、变形菌门、TM7菌门、拟杆菌属、产芽胞菌属和TM-3菌属相对丰度均显著降低(均P<0.05);与DZTH组相比,DZTH+LPS组厚壁菌门、放线菌门、梭状芽胞杆菌属、瘤胃菌属、乳杆菌属、颤螺菌属和双歧杆菌属相对丰度均显著降低,拟杆菌门、变形菌门、TM7菌门、拟杆菌属、产芽胞菌属和TM-3菌属相对丰度均显著升高(均P<0.05)。与NC组相比,HUA组大鼠肾组织中TLR4、p-NF-κB p65蛋白表达均显著增加(均P<0.0Objective To observe the regulatory effect of Dizhuo decoction on intestinal dysbiosis in hyperuricemic rats via the TLR4/NF-κB signaling pathway.Methods Seventy SPF male rats were randomly divided into NC group,HUA group,DZTL group,DZTM group,DZTH group,positive control group,and DZTH+LPS group,with 10 rats in each group.The levels of serum uric acid(SUA),creatinine(Cr),blood urea nitrogen(BUN),xanthine oxidase(XOD)and endotoxin(LPS)in the sera of rats were detected.The pathological changes of kidney tissue were observed with HE staining.Theα-diversity and community structure of intestinal flora were analyzed with 16S rDNA sequencing.The expressions of TLR4 and p-NF-κB p65 proteins in kidney tissue were detected using Western blot.Results Compared with the NC group,the levels of SUA,Cr,BUN,XOD and LPS in the serum of rats in the HUA group significantly increased(all P<0.05).Compared with the HUA group,the levels of SUA,Cr,BUN,XOD and LPS in the sera of rats in the DZTL,DZTM,DZTH and positive control groups significantly decreased.The Shannon index,Sobs index,Chao1 index and Ace index also significantly reduced,with the most significant changes observed in the DZTH and positive control groups(all P<0.05).Compared with the DZTH group,the levels of SUA,Cr,BUN,XOD and LPS in the serum of rats in the DZTH+LPS group significantly increased,and the Shannon index,Sobs index,Chao1 index and Ace index also significantly increased(all P<0.05).Compared with the NC group,the relative abundances of Firmicutes,Actinomycetes,Clostridiaceae,Ruminococcaceae,Lactobacillaceae,Helicobacter and Bifidobacterium in the HUA group significantly reduced,while those of Spirochaetaceae,Bacteroidetes,TM7,Prevotella,Bacillaceae and TM-3 significantly increased(all P<0.05).Compared with the HUA group,the relative abundances of Firmicutes,Actinomycetes,Clostridiaceae,Ruminococcaceae,Lactobacillaceae,Helicobacter and Bifidobacterium in the DZTL,DZTM,DZTH,and positive control groups significantly increased,while those of Spirochaetaceae,Bacter

关 键 词：TLR4/NF-κB信号通路 涤浊汤 高尿酸血症 肠道菌群 

分 类 号：R285.5[医药卫生—中药学]