中国临床药理学杂志2026，Vol.42Issue(7)：968-974,7.DOI:10.13699/j.cnki.1001-6821.2026.07.011
山奈酚通过调控GPX4介导的铁死亡及NLRP3/Caspase-1/GSDMD改善大鼠皮瓣缺血再灌注损伤的机制研究
Research of kaempferol improves rat skin flap ischemia-reperfusion injury by regulating GPX4 mediated iron death and NLRP3/Caspase-1/GSDMD pathway
摘要
Abstract
Objective To investigate the protective effect and underlying mechanism of kaempferol(Kae)on flap ischemia-reperfusion injury(FIRI)in rats by regulating glutathione peroxidase 4(GPX4)-mediated ferroptosis and gasdermin D(GSDMD)-mediated pyroptosis.Methods McFarlane method was used to establish the ischemia-reperfusion model of rat dorsal flap.A total of 91 SPF SD rats were randomly divided into sham group,model group,experimental group,agonist group,inhibitor group,Kae+agonist group and Kae+inhibitor group,with 13 rats in each group.After successful modeling,the experimental group was given kaempferol 50 mg·kg-1 by gavage;the agonist group was intraperitoneally injected with 2 mg·kg-1 NOD like receptor thermoprotein domain associated protein 3(NLRP3)activator once a week;the inhibitor group was intraperitoneally injected with 30 mg·kg-1 disulfiram once a week;the Kae+agonist group received intraperitoneal injection of 2 mg·kg-1 NLRP3 activator+50 mg·kg-1 kaempferol;the Kae+inhibitor group received intraperitoneal injection of 30 mg·kg-1 disulfiram+50 mg·kg-1 kaempferol for 2 weeks.The iron content in tissues was detected by iron content detection kit;the levels of serum interleukin-1 β(IL-1 β)and IL-18 were detected by enzyme linked immunosorbent assay(ELISA);the expressions of proliferating cell nuclear antigen(Ki67)and platelet endothelial cell adhesion molecule-1(CD31)were detected by immunohistochemistry;the protein expressions of GPX4,Caspase-1 and GSDMD-NT were detected by Western blot.Results The flap survival rates of the sham group,model group,experimental group,agonist group,inhibitor group,Kae+agonist group and Kae+inhibitor group were(96.73±1.10)％,(67.04±1.60)％,(85.39±1.22)％,(57.96±1.52)％,(75.80±1.72)％,(80.28±0.95)％and(90.49±0.76)％,respectively;the tissue iron content levels were(11.57±4.89),(68.04±7.64),(43.87±9.13),(85.97±8.41),(47.78±11.11),(69.68±6.17)and(29.36±7.66)μmol·L1;the levels of IL-1 β were(43.83±13.96),(246.02±37.60),(172.19±29.46),(354.39±36.05),(153.56±26.89),(271.13±39.54)and(97.53±24.67)pg·mL-1,respectively;the relative expression levels of CD31 were 6 694.96±711.29,2 126.32±277.21,3 592.33±317.33,484.36±56.24,3 568.83±316.65,1 901.66±383.85 and 4 804.18±360.03,respectively;the relative expression levels of Ki67 were 75.56±6.57,24.11±4.02,37.94±4.08,12.17±2.28,38.01±3.80,24.32±2.76 and 54.65±7.01,respectively;the relative expression levels of GPX4 were 0.92±0.02,0.30±0.07,0.47±0.08,0.12±0.04,0.47±0.08,0.27±0.07 and 0.62±0.13,respectively;the relative expression levels of Caspase-1 were 0.08±0.03,0.40±0.07,0.29±0.04,0.68±0.07,0.28±0.03,0.40±0.06 and 0.18±0.06,respectively;the relative expression levels of GSDMD were 0.06±0.04,0.57±0.05,0.30±0.04,0.93±0.09,0.30±0.03,0.56±0.07 and 0.16±0.02 respectively.There were statistically significant differences in the above indexes between model group and sham group,between experimental group and model group,and between Kae+agonist group,Kae+inhibitor group and experimental group(all P＜0.05).Conclusion Kaempferol can alleviate flap ischemia-reperfusion injury in rats,and its protective effect may be related to upregulating GPX4 expression,inhibiting ferroptosis,and regulating the NLRP3/Caspase-1/GSDMD pyroptosis signaling pathway.关键词
山奈酚/皮瓣缺血再灌注损伤/铁死亡/细胞焦亡/谷胱甘肽过氧化物酶4/消皮素DKey words
kaempferol/flap ischemia-reperfusion injury/ferroptosis/pyroptosis/glutathione peroxidase 4/gasdermin D分类
医药卫生引用本文复制引用
刘涛,顾玉彪,蒋振兴,何志军,李岩,陈文,李金鹏,李非,魏晓涛,白璧辉..山奈酚通过调控GPX4介导的铁死亡及NLRP3/Caspase-1/GSDMD改善大鼠皮瓣缺血再灌注损伤的机制研究[J].中国临床药理学杂志,2026,42(7):968-974,7.基金项目
国家自然科学基金地区项目基金资助项目(81860863、81660544、82460942) （81860863、81660544、82460942）
甘肃省联合科研基金重大项目基金资助项目(25JRRA1218) （25JRRA1218）
甘肃省自然基金资助项目(25JRRA275、25JRRA269) （25JRRA275、25JRRA269）
