海南医科大学学报2025，Vol.31Issue(21)：1630-1638,9.DOI:10.13210/j.cnki.jhmu.20250221.005
基于Nrf2/SLC7A11/GPX4通路调控铁死亡探讨黄连厚朴汤对溃疡性结肠炎模型小鼠的影响
Effect of Huanglian Houpo Decoction on mice with ulcerative colitis based on Nrf2/SLC7A11/GPX4 signal pathway in mediated ferroptosis
摘要
Abstract
Objective:To observe the effects of Huanglian Houpo Decoction(HLHPD)on ulcerative colitis(UC)model mice based on the nuclear factor E2-associated factor 2(Nrf2)/Cystine/Glutamate reverse transporter solute carrier family 7 mem-ber 11(SLC7A11)/glutathione peroxidase 4(GPX4)pathway,and to explore its possible mechanism of action.Methods:A to-tal of 60 mice were randomly divided into 6 groups:the blank group,the model group(DSS group),the Western medicine Sul-fasalazine group,the low-dose,medium-dose and high-dose HLHPD groups(HLHPD-L,HLHPD-M,and HLHPD-H),with 10 mice in each group.The UC model was established using dextran sulfate sodium salt(DSS)except the blank group.After the UC moldel was established,except for the blank group and the model group,which were administered equal volumes of distilled water via gavage,the HLHPD-L,HLHPD-M,HLHPD-H,and Western medicine groups(4 g/kg)were given the respective doses of the HLHPD and drug by gavage once a day for 14 consecutive days.The general conditions and disease activity index of mice were observed.The concentrations of serum cytokines,including IL-6,IL-1β,and TNF-α,were quantified using enzyme-linked immunosorbent assay kits.The levels of MDA,SOD,and GSH were quantitatively analyzed in colonic tissue sam-ples using standardized biochemical assays.Histopathological alterations in colonic tissues were observed through hematoxylin-eosin(H&E)staining.Furthermore,transmission electron microscopy was utilized to examine the ultrastructural characteristics of co-lonic specimens.The protein levels of Nrf2,SLC7A11 and GPX4 in the colon tissue of mice was detected by Western Blot.Results:Compared to the blank group,the disease activity index,the serum levels of IL-6,IL-1β and TNF-α,and MDA in colon tissue were significantly increased in the DSS group,while SOD and GSH contents were significantly decreased(P<0.01).Com-pared to the DSS group,the serum levels of IL-6,IL-1β and TNF-α in each drug intervention groups were decreased(P<0.01),the MDA levels in colon tissue of the HLHPD-M and HLHPD-H were decreased(P<0.01),while the SOD and GSH levels were increased(P<0.05).H&E staining results showed that HLHPD could effectively improve the histopathological damage and reduce the depth and range of tissue necrosis.Transmission electron microscope results showed that the structure of intestinal mu-cosa,microvilli,desmosome,and the connections of intestinal epithelial cells recovered obviously.Western blot results revealed a statistically significant downregulation(P<0.01)in the protein expression levels of Nrf2,SLC7A11,and GPX4 in the DSS group when compared to the blank group.The protein expression levels of Nrf2,GPX4 and SLC7A11 in each group were signifi-cantly increased after administration of HLHPD(P<0.01)when compared to the DSS group.Conclusion:HLHPD can effective-ly improve the inflammatory injury of UC,and its mechanism may be related to the regulation of ferroptosis mediated by the Nrf2/SLC7A11/GPX4 pathway.关键词
黄连厚朴汤/溃疡性结肠炎/铁死亡/Nrf2/SLC7A11/GPX4信号通路Key words
Huanglian Houpo Decoction/Ulcerative colitis/Ferroptosis/Nrf2/SLC7A11/GPX4 signaling pathway分类
中医学引用本文复制引用
高猎防,牛美兰,马俊远,郑梦晓,谷娟,李静,胡晓凤,刘晨,李琛祺,刘家宝..基于Nrf2/SLC7A11/GPX4通路调控铁死亡探讨黄连厚朴汤对溃疡性结肠炎模型小鼠的影响[J].海南医科大学学报,2025,31(21):1630-1638,9.基金项目
This study was supported by the Henan Province Medical Science and Technology Research Program(Joint Construction)Project(LHGJ20190273) （Joint Construction）
National College Students'Innovation and Entrepreneurship Training Program Project(202111834031) （202111834031）
College Students'Innovation and Entrepreneurship Training Program(2023xscxcy084) 河南省医学科技攻关计划(联合共建)项目(LHGJ20190273) （2023xscxcy084）
国家级大学生创新创业训练计划项目(202111834031) （202111834031）
大学生创新创业训练项目(2023xscxcy084) （2023xscxcy084）
