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

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

doi:10.1155/2023/5042953

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

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

Authors

Wenju He¹, Qiang Xi², Huantian Cui³, Pingping Zhang¹, Rui Huang⁴, Taihuan Wang⁴, Dongqiang Wang¹

Affiliations

¹ Department of Integration of Traditional Chinese and Western Medicine, First Central Hospital Affiliated to Nankai University, Tianjin First Central Hospital, Tianjin, China.
² Department of Practice and Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
³ Shandong Provincial Key Laboratory of Animal Cell and Developmental Biology, School of Life Sciences, Shandong University, Qingdao, China.
⁴ Department of Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

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.