Protective effect of sanguinarine on intestinal epithelial barrier in septic rats through modulation of MLCK-MLC signaling pathway
10.3969/j.issn.1000-484X.2025.08.009
- VernacularTitle:血根碱调节MLCK-MLC信号通路对脓毒症大鼠肠上皮屏障的保护作用
- Author:
Lijuan WU
1
;
Fenqiao CHEN
;
Tan'e LIU
;
Lijing SHEN
Author Information
1. 河北省中医院急诊科,石家庄 050011
- Publication Type:Journal Article
- Keywords:
Sanguinarine;
Sepsis;
Intestinal barrier;
Inflammation
- From:
Chinese Journal of Immunology
2025;41(8):1847-1852
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect of sanguinarine(SAG)on the intestinal epithelial barrier in septic rats and to explore the potential mechanism initially.Methods:Rats were divided into Sham group,CLP group,low-dose SAG group(L-SAG group),medium-dose SAG group(M-SAG group)and high-dose SAG group(H-SAG group)according to the random number table method,10 rats in each group.The rat model of sepsis was induced by cecum ligation puncture(CLP)method.HE staining was used to observe the pathological damage of intestinal epithelium.Serum DAO activity was detected by diamine oxidase(DAO)kit.Detec-tion of urinary lactose/mannitol(L/M)ratio by high performance liquid chromatography.Detection of serum TNF-α,IL-6 and IL-1β levels by ELISA.Protein expression levels in intestinal epithelial tissues were detected by Western blot.Results:The intestinal mucosa was intact and the intestinal villi were neatly arranged of rats in the Sham group;the intestinal mucosa of CLP group showed congestion and edema,inflammatory cell infiltration,irregular arrangement of intestinal villi,and enlarged villi gap;the pathological damage of intestinal mucosa in M-SAG group and H-SAG group were reduced to different degrees compared with the CLP group.Chiu's score,se-rum DAO activity and urinary L/M ratio were significantly higher in the CLP group compared with the Sham group;Chiu's score,se-rum DAO activity and urinary L/M ratio were significantly lower in the M-SAG and H-SAG groups compared with the CLP group(P<0.05).The serum TNF-α,IL-6 and IL-1β levels were significantly lower in the CLP group than in the Sham group,while the serum TNF-α,IL-6 and IL-1β levels were significantly higher in the M-SAG and H-SAG groups than in the CLP group(P<0.05).Claudin-3,ZO-1 and ocludin protein expressions were significantly lower in the intestinal epithelium of rats in the CLP group compared with the Sham group,while MLCK,MLC and p-MLC protein expressions were significantly increased.Compared with the CLP group,Claudin-3,ZO-1 and occludin protein expressions were significantly increased in the intestinal epithelium of rats in the M-SAG and H-SAG groups,while MLCK,MLC and p-MLC protein expressions were significantly decreased(P<0.05).Conclusion:SAG can reduce in-testinal barrier damage,inhibit intestinal barrier permeability,and protect intestinal barrier integrity in septic rats,which is at least partially achieved by inhibiting MLCK-MLC signaling pathway activation.
