Effect of Angelica sinensis polysaccharides on intestinal injury in septic rats by regulating AMPK/NLRP3 pathway-mediated pyroptosis
10.12007/j.issn.0258-4646.2024.12.001
- VernacularTitle:当归多糖调控AMPK/NLRP3通路介导的细胞焦亡对脓毒症大鼠肠道损伤的改善作用
- Author:
Hang XIE
1
;
Hua LI
;
Haitao LI
;
Ruoyu SHI
;
Qian CHEN
;
Binbin ZANG
Author Information
1. 河南省中医院(河南中医药大学第二附属医院)重症医学科,郑州 450053
- Publication Type:Journal Article
- Keywords:
Angelica sinensis polysaccharide;
AMPK/NLRP3 pathway;
pyroptosis;
sepsis;
intestinal injury
- From:
Journal of China Medical University
2024;53(12):1057-1063,1070
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of Angelica sinensis polysaccharide (ASP) on intestinal injury in septic rats by regulating the adenosine-monophosphate-activated protein kinase (AMPK)/Nod-like receptor protein 3 (NLRP3) pathway-mediated pyroptosis. Methods A rat model of sepsis was created using cecal ligation and perforation surgery. The successfully modeled rats were separated into a model group;low-,medium-,and high-ASP (ASP-L,ASP-M,ASP-H,respectively) groups;and an AMPK inhibitor group,with 12 rats in each group. Twelve rats in the same period were regarded as the sham group without cecal ligation. Hematoxylin and eosin staining was used to observe the pathological changes in the small intestine of the rats and pathological scoring was performed. TUNEL staining was used to detect intestinal cell pyroptosis;immunohistochemical staining was used to detect NLRP3 expression in small intestine tissue;Enzyme-linked immunosorbent asays were used to determine the serum levels of interleukin (IL)-18 and IL-1β and the activities of D-amino acid oxidase (DAO) and intestinal fatty acid binding protein (iFABP) in the small intestine;and Western blotting was used to determine the levels of gasdermin D (GSDMD),apoptosis-associated speck-like protein containing a CARD (ASC),cleaved caspase-1,and p-AMPK/AMPK proteins in small intestine tissue. Results Compared with the sham group,the model group showed increased small intestine tissue Chiu score;apoptosis rate;and NLRP3,DAO,iFABP,GSDMD,ASC,cleaved caspase-1 and serum IL-18 and IL-1β levels and a decreased p-AMPK/AMPK ratio (P<0.05). Compared to the model group,the ASP-L,ASP-M,and ASP-H groups showed reduced small intestine tissue Chiu score;apoptosis rate;NLRP3,DAO,iFABP,GSDMD,ASC,cleaved caspase-1,and serum IL-18 and IL-1β levels and an increased p-AMPK/AMPK ratio (P<0.05). AMPK inhibitors weakened the inhibitory effect of ASP on small intestine tissue cell apoptosis,and exacerbated intestinal injury (P<0.05). Conclusion ASP inhibited the activation of NLRP3 inflammasomes by activating AMPK expression,thereby inhibiting pyroptosis and alleviating intestinal injury in septic rats.
