Qiandong Zhu,1 Zimu Pan,2 Zhenxing Li,3 Ren Ye,3 Yangyang Zhuang,2 Mei Yang,2 Weiwei Wang,2 Jingye Pan,2,4– 6 Qiuqi Gao2 

1Departments of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325015, People’s Republic of China; 2Department of Intensive Care Unit, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, 325015, People’s Republic of China; 3Department of Traditional Chinese Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, 325015, People’s Republic of China; 4Key Laboratory of Intelligent Treatment and Life Support for Critical Diseases of Zhejiang Province, Wenzhou, Zhejiang, 325015, People’s Republic of China; 5Wenzhou Key Laboratory of Critical Care and Artificial Intelligence, Wenzhou, Zhejiang, 325015, People’s Republic of China; 6Zhejiang Engineering Research Center for Hospital Emergency and Process Digitization, Wenzhou, Zhejiang, 325015, People’s Republic of China

Correspondence: Qiuqi Gao, Email Gaoqiuqi8007@163.com Jingye Pan, Email panjingye@wzhospital.cn

Purpose: This study aimed to evaluate the therapeutic efficacy of Large Chengqi Decoction(LCD) in attenuating sepsis-related intestinal injury by targeting the HMGB1-TLR4 signaling pathway.
Methods: Seventy-five Sprague-Dawley (SD) rats were utilized to establish a septic intestinal injury model, randomized into sham operation, model control, and three treatment groups (LCD0.1, LCD1, LCD10). HMGB1, TLR4, IL-6, and MCP-1 levels in intestinal tissues were assessed via ELISA and Western blotting. Histopathological changes were examined using HE staining of ileum sections.
Results: Compared to the sham group, the model group showed significant elevation of inflammatory markers, confirming successful model establishment. In the LCD1 group, HMGB1 levels were notably higher at 3 and 5 days, accompanied by consistent TLR4 downregulation. IL-6 levels were significantly reduced at 3 days, and MCP-1 levels were lower compared to the sham group. LCD10 group exhibited decreased HMGB1 levels at 5 days and reduced IL-6 levels at 3 days. Immunohistochemical analysis at 3 days post-modeling indicated that LCD1 group expressions of HMGB1, TLR4, NF-κB, and MCP-1 resembled the sham group and significantly differed from the model group. Both LCD1 and LCD10 groups showed improved ileal damage and reduced edema compared to the model group.
Conclusion: LCD effectively mitigates inflammatory responses in septic rats by modulating the HMGB1-TLR4/NF-κB pathway, thereby promoting intestinal repair. Concentrations of 1g/mL and 10g/mL present promising therapeutic strategies for sepsis-related intestinal injury, highlighting the potential of traditional Chinese medicine in sepsis treatment research.

Keywords: large Chengqi decoction, high mobility group protein 1, toll-like receptor 4, sepsis-related intestinal injury, traditional Chinese medicine