Plumbagin protect against sepsis-induced myocardial injury in mice by inhibiting the JAK2/STAT3 signaling pathway to reduce cardiomyocyte pyroptosis
10.12122/j.issn.1673-4254.2024.11.18
- VernacularTitle:白花丹素通过抑制JAK2/STAT3通路减弱焦亡对抗脓毒症心肌损伤
- Author:
Ruoli DU
1
,
2
;
Qi YUN
;
Yiren WANG
;
Xinyu DOU
;
Hongwei YE
;
Jiahui WANG
;
Qin GAO
Author Information
1. 蚌埠医科大学 生理学教研室,安徽 蚌埠 233030
2. 蚌埠医科大学 心脑血管疾病基础与临床重点实验室,安徽 蚌埠 233030
- Keywords:
plumbagin;
sepsis induced myocardial injury;
pyroptosis;
network pharmacology
- From:
Journal of Southern Medical University
2024;44(11):2209-2219
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the mechanism of plumbagin for protecting against sepsis-induced myocardial injury in mice.Methods Network pharmacology analysis was used to obtain the key targets of plumbagin and diseases,which were subjected to GO and KEGG analysis,and the binding energy was verified using molecular docking.In a mouse model of cecal ligation and puncture(CLP),the protective effect of plumbagin treatment prior to CLP against sepsis-induced myocardial injury was evaluated by examination of myocardial function and pathology using echocardiography and HE staining.Serum levels of CK-MB,LDH,MDA,IL-1β and IL-18 and myocardial ROS level in the mice were detected,and Western blotting was used to determine the protein expression levels of STAT3,GSDMD,caspase-11,JAK2,P-STAT3,P-JAK2,GSDMD-N and HMGB1 in the myocardial tissues.Results Five core targets were screened from the 10 intersecting genes.Molecular docking showed strong binding affinity of plumbagin to STAT3,p-STAT3,and JAK2.Compared with the sham-operated mice,the mouse models of CLP-induced sepsis had significantly decreased CO,LVEF,LVFS and SV and increased serum levels of CK-MB,LDH,MDA and myocardial inflammatory factors and ROS.HE staining and Western blotting showed obvious myocardial injury in the septic mice with increased expressions of JAK2/STAT3 signaling pathway and pyroptosis-related proteins(P<0.05).Pretreatment with plumbagin significantly improved cardiac functions of CLP mice,lowered serum levels of CK-MB,LDH,MDA,inflammatory factors and myocardial ROS,and decreased the expression levels of JAK2/STAT3 signaling pathway and pyroptosis-related proteins.Conclusion Plumbagin pretreatment alleviates myocardial injury in septic mice possibly by inhibiting the STAT3 signaling pathway to reduce cardiomyocyte pyroptosis.
