中国病理生理杂志2025，Vol.41Issue(3)：545-554,10.DOI:10.3969/j.issn.1000-4718.2025.03.015
基于网络药理学、分子对接及动物实验探讨芍药苷对脓毒症肠损伤的作用及机制
Study on role and mechanism of paeoniflorin in septic intestinal injury based on network pharmacology,molecular docking and animal experi-ments
摘要
Abstract
AIM:To investigate the effects and underlying mechanisms of paeoniflorin(PF)on lipopolysac-charide(LPS)-induced intestinal injury in septic mice,using a combination of network pharmacology,molecular docking,and animal experiments.METHODS:Network pharmacology was used to identify key active components and therapeutic targets of Red Peony for treating sepsis.Molecular docking was performed to explore the binding affinity be-tween PF and silent information regulator 1(SIRT1).An LPS-induced mouse model of sepsis with intestinal injury was es-tablished.Samples were collected 24 h after modeling,and hematoxylin-eosin(HE)staining was performed to observe pathological changes in intestinal tissues.Chiu's scoring system was utilized to evaluate the extent of intestinal injury.En-zyme-linked immunosorbent assay(ELISA)was employed to measure levels of inflammatory factors in intestinal tissues,including interleukin-1β(IL-1β)and IL-18,as well as indicators of intestinal permeability such as diamine oxidase(DAO)and intestinal-type fatty acid-binding protein(I-FABP),alongside serum levels of D-lactate and the aerobic gly-colysis product L-lactate.Western blot analysis was performed to assess changes in protein levels of SIRT1,M2-type pyru-vate kinase(PKM2),and NOD-like receptor protein 3(NLRP3)in intestinal tissues.RESULTS:Network pharmacolo-gy suggested that paeoniflorin,an active component of Red Peony,treats sepsis by targeting SIRT1 among other proteins.Molecular docking revealed a strong binding affinity of PF with SIRT1.In vivo experimentation revealed significant patho-logical damage in intestinal tissues in the LPS group compared to the control group as evidenced by HE staining.Chiu's score,along with levels of IL-1β,IL-18,D-lactate,and L-lactate were significantly elevated,while DAO and I-FABP levels were reduced(P＜0.05).SIRT1 expression decreased,while PKM2 and NLRP3 levels increased(P＜0.05).In contrast,the LPS+PF group displayed reduced intestinal histopathological injury,lower Chiu's scores,and decreased levels of IL-1β,IL-18,D-lactate,and L-lactate,along with increased DAO and I-FABP levels(P＜0.05).Notably,SIRT1 protein expression increased while PKM2 and NLRP3 levels decreased(P＜0.05).Furthermore,compared to the LPS+PF group,the LPS+PF+EX527 group exhibited exacerbated intestinal histopathological injury,increased Chiu's scores,as well as elevated levels of IL-1β,IL-18,D-lactate,and L-lactate,alongside reduced DAO and I-FABP levels(P＜0.05),decreased SIRT1 expression,and increased PKM2 and NLRP3 levels(P＜0.05).CONCLUSION:Paeoni-florin effectively alleviates intestinal injury in mice with sepsis,potentially through the upregulation of SIRT1 expression and the inhibition of PKM2-mediated aerobic glycolysis,which subsequently reduces the activation of NLRP3 inflamma-somes,mitigates the release of inflammatory factors,and lessens intestinal inflammation.关键词
脓毒症/肠损伤/芍药苷/沉默信息调节因子1/M2型丙酮酸激酶Key words
sepsis/intestinal injury/paeoniflorin/silent information regulator 1/M2-type pyruvate kinase分类
医药卫生引用本文复制引用
雷娇,张铭,龚禹,李若男,谢菁,张彬枫,马玉清..基于网络药理学、分子对接及动物实验探讨芍药苷对脓毒症肠损伤的作用及机制[J].中国病理生理杂志,2025,41(3):545-554,10.基金项目
甘肃省自然科学基金资助项目(No.24JRRA1075) （No.24JRRA1075）
兰州大学第一医院院内基金(No.ldyyyn2022-5) （No.ldyyyn2022-5）
