涉及远端穿支皮瓣的手术后,血管坏死通常是并发症。二氢辣椒素(DHC)可以保护组织免受缺血再灌注(I/R)损伤,但其在多区穿支皮瓣中的具体作用尚不清楚。在这项研究中,使用网络药理学分析预测I/R损伤背景下DHC的前瞻性目标.通过存活面积分析确定皮瓣活力,激光多普勒血流,血管造影,和组织学检查。血管生成的表现,凋亡,NLR家族pyrin结构域含3(NLRP3)炎性体,氧化应激,和分子相关的环磷酸鸟苷(GMP)-腺苷一磷酸合成酶(cGAS)-干扰素基因刺激(STING)途径使用蛋白质印迹进行评估,免疫荧光,TUNEL染色,和二氢乙锭(DHE)染色。我们的发现显示DHC促进了穿支皮瓣的存活,涉及到cGAS-STING途径,氧化应激,NLRP3炎性体,凋亡,和血管生成。DHC诱导抗氧化应激和抑制NLRP3炎性体,防止血管内皮细胞凋亡。通过STING途径的调节,DHC控制缺血皮瓣中内皮细胞的氧化应激和NLRP3水平。然而,cGAS-STING途径的激活导致活性氧(ROS)和NLRP3炎性体的积累,从而降低DHC的保护作用。DHC通过抑制cGAS-STING通路增强多域穿支皮瓣的存活,氧化应激,和NLRP3炎性体的形成。这些发现揭示了促进多域穿支皮瓣存活的潜在新机制,具有临床意义。
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. DHC enhanced the survival of multidomain perforator flaps by suppressing the cGAS-STING pathway, oxidative stress, and the formation of NLRP3 inflammasome. These findings unveil a potentially novel mechanism with clinical significance for promoting the survival of multidomain perforator flaps.