首页|解毒化瘀颗粒对肝衰竭大鼠miR-146a-5p/NF-κB途径及肠道菌群的干预效应研究

解毒化瘀颗粒对肝衰竭大鼠miR-146a-5p/NF-κB途径及肠道菌群的干预效应研究

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目的 探讨解毒化瘀颗粒对急性肝衰竭大鼠的miR-146a-5p/NF-κB途径及肠道菌群结构的干预效应。方法 构建急性肝衰竭大鼠模型(Model),并予以解毒化瘀颗粒(JDHY)、抗生素复合物(ABX)干预,48h后取材进行病理、qPCR、16S rRNA等检测。结果 病理检测显示肝衰竭大鼠的肝组织出现不同程度的肝细胞坏死,残存肝细胞的PCNA蛋白表达减少,与Control组比较,Model组大鼠肝组织PCNA蛋白表达显著下降(P<0。001),与Model组比较,JDHY组、ABX组大鼠肝组织的PCNA蛋白表达显著上升(P<0。001)。FISH检测发现miR-146a-5p与NF-κB发生交互作用。与Model组比较,JDHY组、ABX组的miR-146a-5p的基因水平显著上升,TNF-α、IL-1β、TRL4的基因水平下降;Model组的NF-κB的基因水平与JDHY组比较有显著性差异(P<0。05)。16S rRNA检测显示Model组以变形菌门为主,而正常组、JDHY组、ABX组以厚壁菌门、拟杆菌门为主;α、β多样性分析显示各组大鼠肠道菌群的相对丰富度、特征微生物及多样性具有显著性差异。结论 解毒化瘀颗粒可能调控miR-146a-5p/NF-κB途径并能够改善肝衰竭大鼠肠道微生态失衡发挥增强肝再生、拮抗肝衰竭的疗效作用。
Intervention effect of Jiedu Huayu Granules regulating miR-146a-5p/NF-κB/intestinal flora against liver failure
Objective To investigate the effects of Jiedu Huayu Granules on miR-146a-5p/NF-κB pathway and intestinal flora in rats with acute liver failure.Methods The rat Model of acute liver failure was constructed and treated with Jiedu Huayu granules(JDHY)and antibiotic complex(ABX).After 48h,the samples were collected for pathology,qPCR and 16S rRNA detection.Results HE and IHC staining showed that the liver tissue structure of rats with liver failure showed a large number of liver cells necrosis to varying de-grees,and the expression of PCNA protein in the surviving liver cells was decreased.Compared with the Control group,the expression of PCNA protein in the liver tissue of rats in the Model group was significantly decreased(P<0.001).The expression of PCNA protein in liver tissue of rats in JDHY group and ABX group was significantly increased(P<0.01 and P<0.05).FISH detected the interaction between miR-146a-5p and NF-κB.Compared with Model group,the gene levels of miR-146a-5p in JDHY group and ABX group were significantly increased,while the gene levels of TNF-α,IL-1 β and TRL4 were decreased.The NF-κB gene level in Model group was significantly different from that in JDHY group(P<0.05).16S rRNA detection showed that Proteobacteria were dominant in Model group,while Firmicutes and Bacteroidetes were dominant in normal group,JDHY group and ABX group.α and β diversity analy-sis showed that there were significant differences in the relative richness,characteristic microorganisms and diversity of intestinal flora a-mong all groups.Conclusion Jiedu Huayu granules may regulate the miR-146a-5p/NF-κB pathway and improve the intestinal micro-ecological imbalance in rats with liver failure,which can enhance liver regeneration and antagonize liver failure.

Jiedu Huayu GranulesAcute liver failure ratsmiR-146a-5p/NF-κB pathwayIntestinal floraLiver regen-eration

蓝艳梅、陆正峰、毛德文、张荣臻、王娜、严惠萍、王明刚、吴凤兰、林玉培、刘好

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广西中医药大学第一附属医院,中医临床研究重点实验室,广西南宁 530023

广西医科大学附属民族医院,广西南宁 530001

解毒化瘀颗粒 急性肝衰竭 miR-146a-5p/NF-κB途径 肠道菌群 肝再生

2024

时珍国医国药
时珍国医国药杂志社

时珍国医国药

北大核心
影响因子:0.887
ISSN:1008-0805
年,卷(期):2024.35(15)