This study investigated the relationship between endothelial pyroptosis and the occurrence of systemic inflammatory response (SIR) after radiofrequency (RF) ablation of hepatic hemangiomas. Thirty-two patients with hepatic hemangiomas were treated with RF ablation and blood samples of the patients were collected at different time points. Immunohistochemistry staining was performed to evaluate the expression of caspase-1, gasdermin D (GSDMD), IL-1β and IL-18 in hepatic hemangioma and subablated hemangioma tissue. In vitro experiments, human umbilical vein endothelial cells (HUVECs) were treated with sub-ablative hyperthermia with or without the addition of caspase-1 inhibitor, Ac-YVAD-CMK in the medium. Lactate dehydrogenase (LDH), IL-18, IL-1β, caspase-1 and GSDMD were measured by enzyme-linked immunosorbent assay, real-time PCR and Western blot methods. An elevation of general SIR parameters (CRP and WBC), pyroptosis-related inflammatory cytokines (IL-1β and IL-18) and LDH were observed 1-day post-RF ablation and their peak values were significantly correlated with ablated volume (p < .001) and ablation time (p < .001). Moreover, levels of pyroptosis-related inflammatory cytokines correlated well with general SIR parameters, respectively (p < .001). Immunohistochemical analysis showed the increased expression of caspase-1, GSDMD, IL-18 and IL-1β in the endothelial cells of subablated hemangioma. In vitro experiments showed that subablative hyperthermia induced the caspase-1-associated endothelial pyroptosis and Ac-YVAD-CMK attenuated pyroptosis. In conclusion, SIR in patients treated by RF ablation for hepatic hemangiomas was significantly associated with the ablated volume and ablation time and endothelial pyroptosis may involve in the occurrence of SIR following RF ablation of hepatic hemangiomas.

这项研究调查了肝血管瘤射频消融后内皮细胞焦磷酸化与全身炎症反应（SIR）发生之间的关系。32例肝血管瘤患者接受射频消融治疗，并在不同时间点采集患者血液。进行免疫组织化学染色以评估肝血管瘤和消融性血管瘤组织中caspase-1，gasdermin D（GSDMD），IL-1β和IL-18的表达。在体外实验中，用亚烧蚀性高温治疗人脐静脉内皮细胞（HUVEC），在介质中添加或不添加caspase-1抑制剂Ac-YVAD-CMK。酶联免疫吸附法测定乳酸脱氢酶（LDH），IL-18，IL-1β，caspase-1和GSDMD，实时PCR和Western印迹方法。射频消融后1天观察到一般SIR参数（CRP和WBC），与凋亡相关的炎性细胞因子（IL-1β和IL-18）和LDH升高，并且它们的峰值与消融量显着相关（p  <.001）和消融时间（p  <.001）。此外，与凋亡相关的炎性细胞因子的水平分别与一般SIR参数相关性很好（p  <.001）。免疫组织化学分析显示，消融性血管瘤内皮细胞中caspase-1，GSDMD，IL-18和IL-1β表达增加。体外实验表明，亚烧蚀性热疗诱导了caspase-1相关的内皮细胞凋亡，而Ac-YVAD-CMK减弱了细胞凋亡。总之，经射频消融治疗肝血管瘤的患者的SIR与消融量和消融时间显着相关，并且内皮细胞凋亡可能与射频消融肝血管瘤后发生SIR有关。