Gongying-Jiedu-Xiji recipe promotes the healing of venous ulcers by inhibiting ferroptosis via the CoQ-FSP1 axis.

Gongying-Jiedu-Xiji recipe promotes the healing of venous ulcers by inhibiting ferroptosis via the CoQ-FSP1 axis.
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DOI:
10.3389/fphar.2023.1291099
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发表时间:
2023
影响因子:
5.6
通讯作者:
--
中科院分区:
医学2区
文献类型:
--
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目的:宫营解毒习集方(DDL,批号Z01080175)具有降体温、解毒、活血、消肿、祛腐、化脓等功效。本研究旨在探讨DDL治疗静脉性溃疡的作用机制。方法:收集经伦理学批准的9例VU患者DDL治疗前后的正常组织和VU组织。采用普鲁士蓝铁染色、免疫印迹、免疫组织化学、免疫荧光和实时定量聚合酶链式反应检测铁下垂抑制蛋白1(FSP1)、辅酶Q(CoQ)、4-羟基壬烯醛(4-HNE)和谷胱甘肽过氧化物酶4(Gpx4)的表达。在成功建立人包皮成纤维细胞(HFF)铁下垂模型后,加入冻干DDL粉,对细胞进行活性检测、免疫印迹、流式细胞仪、谷胱甘肽(GSH)和丙二醛(MDA)检测、电子显微镜和qPCR检测。结果:VU组织下垂较正常组织明显加重,DDL治疗后VU组织下垂较治疗前减弱。抑制辅酶Q和FSP1的表达以及FSP1的转染会影响DDL的作用。结论:DDL可能通过调节辅酶Q-FSP1轴促进VU愈合。
Objective: Gongying-Jiedu-Xiji recipe (DDL, batch number Z01080175) reduces body temperature, detoxifies, activates the blood circulation, reduces swelling, and dispels decay and pus. The aim of this study was to investigate the mechanism of action by which DDL functions in the treatment of venous ulcers (VUs). Methods: Normal tissues as well as VU tissues before and after DDL treatment were collected from nine VU patients in the hospital with ethical approval. These three tissues were subjected to Prussian blue iron staining, immunoblotting, immunohistochemistry, immunofluorescence, and quantitative real-time PCR to detect the expression of ferroptosis suppressor protein 1 (FSP1), coenzyme Q (CoQ), 4-hydroxynonenal (4-HNE), and glutathione peroxidase 4 (GPX4). After successful validation of the heme-induced human foreskin fibroblast (HFF) ferroptosis model, lyophilized DDL powder was added to the cells, and the cells were subjected to viability assays, immunoblotting, flow cytometry, glutathione (GSH) and malonaldehyde (MDA) assays, electron microscopy and qPCR assays. Results: Ferroptosis in VU tissues was stronger than that in normal tissues, and ferroptosis in VU tissues after DDL treatment was weaker than that before treatment. Inhibition of CoQ and FSP1 and transfection of FSP1 influenced the effects of DDL. Conclusion: Our results suggest that DDL may promote healing by attenuating ferroptosis in VUs and that DDL may promote VU healing by modulating the CoQ-FSP1 axis.
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发表时间: 2014-12
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DOI: 10.1186/s13063-023-07547-y
发表时间: 2023-08-02
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