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凉血化瘀方通过抑制依赖于肽基精氨酸脱亚氨酶4的中性粒细胞胞外诱捕网形成改善盲肠结扎和穿刺诱导的脓毒症模型大鼠的凝血功能障碍

Liang-Ge Decoction Ameliorates Coagulation Dysfunction in Cecal Ligation and Puncture-Induced Sepsis Model Rats through Inhibiting PAD4-Dependent Neutrophil Extracellular Trap Formation.

作者信息

He Wenju, Xi Qiang, Cui Huantian, Zhang Pingping, Huang Rui, Wang Taihuan, Wang Dongqiang

机构信息

Department of Integration of Traditional Chinese and Western Medicine, First Central Hospital Affiliated to Nankai University, Tianjin First Central Hospital, Tianjin, China.

Department of Practice and Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

出版信息

Evid Based Complement Alternat Med. 2023 Apr 29;2023:5042953. doi: 10.1155/2023/5042953. eCollection 2023.

DOI:10.1155/2023/5042953
PMID:37159591
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10163969/
Abstract

Liang-Ge (LG) decoction could ameliorate coagulation dysfunction in septic model rats. However, the mechanism of LG in treating sepsis still needs to be clarified. Our current study established a septic rat model to evaluate the effect of LG on coagulation dysfunction in septic rats first. Second, we investigated the effect of LG on NET formation in septic rats. Finally, NETs and PAD4 inhibitors were further used to clarify if LG could improve the mechanism of sepsis coagulation dysfunction by inhibiting NET formation. Our findings indicated that treatment with LG improved the survival rate, reduced inflammatory factor levels, enhanced hepatic and renal function, and reduced pathological changes in rats with sepsis. LG could also alleviate coagulation dysfunction in septic model rats. Besides, LG treatment reduced NETs formation and decreased PAD4 expression in neutrophiles. In addition, LG treatment showed a similar result in comparison to the treatment with either NET inhibitors or PAD4 inhibitors alone. In conclusion, this study confirmed that LG has therapeutic effects on septic rats. Furthermore, the improvement of coagulation dysfunction in septic rats by LG was achieved through inhibiting PAD4-mediated NET formation.

摘要

凉血化瘀方(LG)可改善脓毒症模型大鼠的凝血功能障碍。然而,LG治疗脓毒症的机制仍需阐明。我们目前的研究首先建立了脓毒症大鼠模型,以评估LG对脓毒症大鼠凝血功能障碍的影响。其次,我们研究了LG对脓毒症大鼠中性粒细胞胞外诱捕网(NET)形成的影响。最后,进一步使用NET和瓜氨酸化作用4(PAD4)抑制剂来阐明LG是否可以通过抑制NET形成来改善脓毒症凝血功能障碍的机制。我们的研究结果表明,LG治疗可提高脓毒症大鼠的生存率,降低炎症因子水平, 增强肝肾功能,并减轻脓毒症大鼠的病理变化。LG还可以缓解脓毒症模型大鼠的凝血功能障碍。此外,LG治疗可减少NET形成,并降低中性粒细胞中PAD4的表达。此外,与单独使用NET抑制剂或PAD4抑制剂治疗相比,LG治疗显示出类似的结果。总之,本研究证实LG对脓毒症大鼠具有治疗作用。此外,LG通过抑制PAD4介导的NET形成来改善脓毒症大鼠的凝血功能障碍。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0cb/10163969/97aa1f6f7bc9/ECAM2023-5042953.008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0cb/10163969/27addf78950c/ECAM2023-5042953.001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0cb/10163969/97aa1f6f7bc9/ECAM2023-5042953.008.jpg

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