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| Paeonol alleviates rat skin flap ischemia-reperfusion injury by reducing endothelial cell pyroptosis via regulating p38MAPK-Nrf2 signaling pathway |
| Hits 21 Download times 5 Received:December 15, 2025 |
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| DOI
10.11656/j.issn.1673-9043.2026.04.08 |
| Key Words
paeonol;p38 mitogen-activated protein kinase;rat;skin flap;ischemia-reperfusion injury;oxidative stress |
| Author Name | Affiliation | | CHEN Yuhong | Department of Hand and Trauma Surgery, The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha 410000, China | | ZHOU Qing | Department of Hand and Trauma Surgery, The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha 410000, China | | TANG Qingni | Department of Hand and Trauma Surgery, The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha 410000, China | | CHEN Jiaofeng | Department of Hand and Trauma Surgery, The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha 410000, China |
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| Abstract
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| [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. |
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