Effect of Huishen Suxing Decoction on Intestinal Mucosal Barrier in Acute-on-Chronic Liver Failure Rats by Regulating HMGB1/TLR4 Signaling Pathway
- VernacularTitle:回神塑形汤通过调控HMGB1/TLR4信号通路对慢加急性肝衰竭大鼠肠黏膜屏障的保护作用
- Author:
Chao LYU
1
;
Huiping YAN
;
Qian QIN
Author Information
- Publication Type:Journal Article
- Keywords: Acute-on-chronic liver failure; Huishen Suxing decoction; HMGB1/TLR4 signaling pathway; Intestinal mucosal barrier; Protective effect
- From: World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(9):2636-2645
- CountryChina
- Language:Chinese
- Abstract: Objective To investigate the protective effect of Huishen Suxing decoction on intestinal mucosal barrier in rats with acute-on-chronic liver failure(ACLF)and elucidate its possible mechanism.Methods The rats were randomly divided into control group(Con group),model group,Bifico group(positive control),and HSD-L,M and H groups(low,medium and high dose of Huishen Suxing decoction).The ACLF model was established by CCl4 combined with D-galactosamine(D-Gal N).Intragastric administration of CCl4 was started on the 6th week of intraperitoneal injection,once daily for 6 weeks,and continued until the acute challenge with D-Gal N injection.The liver function of rats was detected by kits.HE staining was used to observe the pathological changes of liver tissue and ileum tissue.The levels of endotoxin(ET),diamine oxidase(DAO),IL-1β,IL-6,TNF-α in serum and secretory immunoglobulin A(sIgA)in ileum were detected by ELISA.Intestinal mucosal permeability was detected by FITC-Dextran tracer.Selective medium was used to detect the amount of intestinal flora.Western blotting was used to detect the protein expression levels of HMGB1,TLR4,NF-κB p65,p-NF-κB p65,Occludin and ZO-1 in ileum tissue of each group.Results Compared with the Con group,the liver tissue and ileum tissue of the Model group showed obvious pathological damage.The levels of ALT,AST,TBIL,ET,DAO,IL-1β,IL-6 and TNF-α in serum significantly increased(P<0.01).The content of sIgA in ileum tissue significantly decreased(P<0.01).The permeability of intestinal mucosa and the number of Enterobacter and Enterococcus in the intestine significantly increased(P<0.01).The amount of Bifidobacterium and Lactobacillus significantly decreased(P<0.01).The expressions of HMGB1,TLR4 protein and p-NF-κB p65/NF-κB p65 protein ratio in ileum tissue significantly increased(P<0.01),and the expressions of Occludin and ZO-1 protein significantly decreased(P<0.01).Compared with the model group,the Bifico group and HSD-L,M,H groups had significantly alleviated liver and ileum injury.The levels of ALT,AST,TBIL,ET,DAO,IL-1β,IL-6 and TNF-α in serum significantly decreased(P<0.01).The permeability of intestinal mucosa and the amount of Enterobacteriaceae and Enterococcus in the intestine significantly decreased(P<0.01),while the amount of Bifidobacterium and Lactobacillus significantly increased(P<0.01).The expressions of HMGB1,TLR4 protein and p-NF-κB p65/NF-κB p65 protein ratio in ileum tissue significantly decreased(P<0.01),and the expressions of Occludin and ZO-1 protein significantly increased(P<0.01).Conclusion Huishen Suxing decoction can reduce inflammatory response,regulate the structure of intestinal flora,improve the intestinal mucosal barrier,and thus alleviate liver injury in ACLF rats.The mechanism may be associated to the inhibition of HMGB1/TLR4/NF-κB signaling pathway activation.
