Effects of PPARδ agonist GW501516 on the intestinal mucosal barrier in septic mice by regulating autophagy
10.12007/j.issn.0258-4646.2025.03.011
- VernacularTitle:PPARδ激动剂GW501516调控细胞自噬对脓毒症小鼠肠黏膜屏障的影响
- Author:
Kaili CHEN
1
;
Ting WANG
1
;
Zhihao LUO
1
Author Information
1. 广东省中医院海南医院急诊科,海口 570203
- Publication Type:Journal Article
- Keywords:
sepsis;
GW501516;
peroxisome proliferator activated receptor δ;
autophagy;
intestinal mucosal barrier injury
- From:
Journal of China Medical University
2025;54(3):246-250,256
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the mechanism of action of GW501516 on the intestinal mucosal barrier of septic mice.Methods Septic mice were divided into four groups:model,GW501516,GW501516+Rap,and a sham group.Hematoxylin and eosin staining was used to observe the pathological injury of the small intestinal mucosa.D-lactate(D-LA)and diamine oxidase(DAO)levels in serum,as well as secreted immunoglobulin A(sIgA)and inflammatory factor levels in small intestinal tissues,were measured using the enzyme-linked immunosorbent assay.The number of autophagosomes in the intestinal tissue was determined using transmission electron microscopy.Peroxisome proliferator activated receptor δ(PPARδ)and autophagy-related protein expression levels in small intestinal tis-sues were assessed using Western blotting.Results Compared with mice in the sham group,those in the model group exhibited severe intestinal mucosal injury,significantly higher D-LA and DAO serum levels,elevated sIgA and inflammatory factor levels in the small intes-tinal tissues,excessive autophagy in the small intestinal tissues,and significantly lower PPARδ protein levels(all P＜0.05).Compared with the model group,intestinal mucosal injury was significantly reduced in the GW501516 group,with a significant decrease in serum D-LA and DAO levels,as well as reduced sIgA and inflammatory factor levels in small intestinal tissues.Excessive autophagy in small intes-tinal tissues was inhibited,and PPARδ protein levels were significantly increased(all P＜0.05).However,Rap significantly inhibited the ameliorative effects of GW501516 on the intestinal mucosal injury in septic mice.Conclusion The PPARδ agonist GW501516 improves intestinal mucosal barrier damage in septic mice by inhibiting autophagy.
