Dihydrocapsaicin suppresses the STING ‐mediated accumulation of ROS and NLRP3 inflammasome and alleviates apoptosis after ischemia–reperfusion injury of perforator skin flap

作者：Yingying Lai, Ningning Yang, Xuankuai Chen, Xianhui Ma, Zhuliu Chen, Chengji Dong, Gaoxiang Yu, Yingying Huang, Donghao Shi, Pin Fang, Kejian Fu, Renhao Jiang, Cong Mao, Jian Ding, Weiyang Gao · 发表于：Phytotherapy Research · 年份：2024 · DOI：10.1002/ptr.8167 · 被引用次数：25 · 研究领域：Inflammasome and immune disorders、interferon and immune responses、S100 Proteins and Annexins

Avascular necrosis frequently occurs as a complication following surgery involving the distal perforator flap. Dihydrocapsaicin (DHC) can protect tissue from ischemia-reperfusion (I/R) injury, but its specific role in multizone perforator flaps remains unclear. In this study, the prospective target of DHC in the context of I/R injury was predicted using network pharmacology analysis. Flap viability was determined through survival area analysis, laser Doppler blood flow, angiograms, and histological examination. The expressions of angiogenesis, apoptosis, NLR family pyrin domain containing 3 (NLRP3) inflammasome, oxidative stress, and molecules related to cyclic guanosine monophosphate (GMP)-adenosine monophosphate synthase (cGAS)-interferon gene stimulant (STING) pathway were assessed using western blotting, immunofluorescence, TUNEL staining, and dihydroethidium (DHE) staining. Our finding revealed that DHC promoted the perforator flap survival, which involves the cGAS-STING pathway, oxidative stress, NLRP3 inflammasome, apoptosis, and angiogenesis. DHC induced oxidative stress resistance and suppressed the NLRP3 inflammasome, preventing apoptosis in vascular endothelial cells. Through regulation of STING pathway, DHC controlled oxidative stress in endothelial cells and NLRP3 levels in ischemic flaps. However, activation of the cGAS-STING pathway led to the accumulation of reactive oxygen species (ROS) and NLRP3 inflammasome, thereby diminishing the protective role of DHC. D...