天津中医药大学学报2026，Vol.45Issue(4)：428-435,8.DOI:10.11656/j.issn.1673-9043.2026.04.08
丹皮酚调控p38MAPK-Nrf2信号通路减轻内皮细胞焦亡影响大鼠皮瓣缺血再灌注损伤机制
Paeonol alleviates rat skin flap ischemia-reperfusion injury by reducing endothelial cell pyroptosis via regulating p38MAPK-Nrf2 signaling pathway
摘要
Abstract
[Objective]To explore the mechanism of paeonol in improving skin flap ischemia-reperfusion injury(I/R)in rats.[Methods]Sixty male Sprague-Dawley rats were randomly divided into four groups:sham group,I/R group,paeonol group,and paeonol+ML385 group,with 15 rats in each group.Except for the sham group,the other groups were used to establish flap I/R injury models.The paeonol group and paeonol+ML385 group were treated with 50 mg/kg paeonol.The paeonol+ML385 group was intraperitoneally injected with 30 mg/kg ML385.After 7 days,the survival area of the rat flaps and blood flow in the flaps were analyzed.The expressions of actin alpha cardiac muscle 2(ACTA2),CD31,and the N-terminal domain of gasdermin D(GSDMD-N)in the flaps were analyzed by immunofluorescence staining.Reactive oxygen species(ROS)levels were analyzed by dihydroethidium staining.The p38 mitogen-activated protein kinase(p38MAPK)-nuclear factor E2-related factor 2(Nrf2)signaling pathway was analyzed by Western blot.[Results]Compared with the sham group,the I/R group showed significantly decreased flap survival area,flap blood flow signal intensity,area of CD31 and ACTA2 co-localized positive vessels,and protein expressions of vascular endothelial growth factor(VEGF)and matrix metalloproteinase 9(MMP9)(P<0.05),while the number of CD31 and GSDMD-N co-localized positive cells was significantly increased(P<0.05).Compared with the I/R group,the paeonol group showed significantly increased flap survival area,flap blood flow signal intensity,area of CD31 and ACTA2 co-localized positive vessels,and protein expressions of VEGF and MMP9(P<0.05),while the number of CD31 and GSDMD-N co-localized positive cells was significantly decreased(P<0.05).The relative fluorescence intensity of ROS and malondialdehyde(MDA)level in the flap of the paeonol group were significantly lower than those in the I/R group(P<0.05),while the glutathione(GSH)level was significantly higher(P<0.05).Compared with the paeonol group,the paeonol+ML385 group showed significantly decreased Nrf2 protein expression(P<0.05)and significantly increased p-p38 protein expression(P<0.05)in the flaps.Furthermore,the addition of ML385 reversed the beneficial effects of paeonol on flap survival area,blood flow signal intensity,angiogenesis,pyroptosis,and oxidative stress in the rat flap I/R model.[Conclusion]Paeonol protects dermal vascular endothelial cells from oxidative stress injury and reduces pyroptosis by enhancing the antioxidant defense system in rats with flap I/R injury.Its mechanism may be related to the regulation of the p38MAPK-Nrf2 signaling pathway.关键词
丹皮酚/P38丝裂原激活蛋白激酶/大鼠/皮瓣/缺血再灌注损伤/氧化应激Key words
paeonol/p38 mitogen-activated protein kinase/rat/skin flap/ischemia-reperfusion injury/oxidative stress分类
医药卫生引用本文复制引用
陈宇虹,周青,唐庆妮,陈姣凤..丹皮酚调控p38MAPK-Nrf2信号通路减轻内皮细胞焦亡影响大鼠皮瓣缺血再灌注损伤机制[J].天津中医药大学学报,2026,45(4):428-435,8.基金项目
湖南省卫生健康委员会科研项目(20241317). （20241317）
