中国中医急症2025，Vol.34Issue(7)：1138-1142,5.DOI:10.3969/j.issn.1004-745X.2025.07.003
炎调方调节AMPK/SIRT1/PGC-1α信号通路对脓毒症大鼠肠屏障损伤的影响
Effect of Yantiao Formula on Intestinal Barrier Injury in Sepsis Rats via Regulating the AMPK/SIRT1/PGC-1α Signaling Pathway
摘要
Abstract
Objective:To investigate the effect of Yantiao Formula on intestinal barrier injury in septic rats by modulating the 5'-adenosine monophosphate-activated protein kinase(AMPK)/silent information regulator-related enzyme 1(SIRT1)/peroxisome proliferator-activated receptor γ coactivator 1α(PGC-1α)signaling pathway.Meth-ods:A rat model of sepsis was established using cecal ligation and puncture(CLP).The animals were randomly divided into 5 groups:model group,Yantiao Formula group(9.8 g/kg),compound C(CC,AMPK inhibitor,0.2 mg/kg)group,Yantiao Formula+CC group,with 12 rats in each group.Another 12 rats underwent sham surgery and served as the sham group.After treatment with Yantiao Formula and/or CC,sepsis scores were evaluated.Intesti-nal permeability was assessed by intraintestinal perfusion with fluorescein isothiocyanate(FITC)-dextran.Histologi-cal changes including intestinal mucosal thickness and villus height were analyzed using HE staining.Serum lev-els of inflammatory cytokines IL-1β,IL-6,and IL-18 were measured by ELISA.Expression levels of tight junc-tion proteins and key proteins in the AMPK/SIRT1/PGC-1α pathway in intestinal tissues were detected by West-ern blotting.Results:Compared with the sham group,the model group showed significantly increased sepsis scores,serum FITC-dextran,and levels of IL-1β,IL-6,and IL-18(P＜0.05).In contrast,intestinal mucosal thick-ness,villus height,and expression levels of ZO-1,claudin-1,occludin,SIRT1,PGC-1α,and phosphorylated AMPK/total AMPK(p-AMPK/AMPK)were significantly decreased(P＜0.05).Compared with the model group,the Yantiao Formula group exhibited reduced serum FITC-dextran and inflammatory cytokine levels(P＜0.05),along with improved mucosal thickness,villus height,and upregulated expression of ZO-1,claudin-1,occludin,SIRT1,PGC-1α,and p-AMPK/AMPK(P＜0.05).In contrast,the CC group showed elevated serum FITC-dextran and cy-tokine levels(P＜0.05),with further decreases in mucosal thickness,villus height,and protein expression levels(P＜0.05).Compared with the Yantiao Formula group,the Yantiao Formula+CC group showed increased serum FITC-dextran and cytokine levels(P＜0.05),while mucosal thickness,villus height,and expression of ZO-1,clau-din-1,occludin,SIRT1,PGC-1α,and p-AMPK/AMPK were significantly reduced(P＜0.05).Conclusion:Yan-tiao Formula can inhibit systemic inflammation and alleviate intestinal barrier injury in septic rats,potentially through activation of the AMPK/SIRT1/PGC-1α signaling pathway.关键词
脓毒症/炎调方/AMPK/SIRT1/PGC-1α/肠屏障损伤/大鼠Key words
Sepsis/Yantiao Formula/AMPK/SIRT1/PGC-1α/Intestinal barrier injury/Rats分类
医药卫生引用本文复制引用
韩丹,周桢,陈天阳,许婉,吴琪琪,王倍倍,方荣..炎调方调节AMPK/SIRT1/PGC-1α信号通路对脓毒症大鼠肠屏障损伤的影响[J].中国中医急症,2025,34(7):1138-1142,5.基金项目
国家自然科学基金项目(82074156) （82074156）
上海市卫健委科研课题(20204Y0473) （20204Y0473）
