Renshen Baidusan Protects Mucosal Barrier in Ulcerative Colitis via AMPK/ULK1 Autophagy Pathway
10.13422/j.cnki.syfjx.20222142
- VernacularTitle:基于AMPK/ULK1自噬通路探讨人参败毒散对溃疡性结肠炎黏膜屏障的干预机制
- Author:
Peiyu XIONG
1
;
Chun ZHONG
2
;
Peixu ZHANG
1
;
Xinglong LIU
1
;
Xu CHEN
1
;
Bo JIA
1
Author Information
1. School of Basic Medical Sciences， Chengdu University of Traditional Chinese Medicine（TCM）， Chengdu 610075， China
2. Sichuan Second Hospital of TCM， Chengdu 610014， China
- Publication Type:Journal Article
- Keywords:
Renshen Baidusan;
ulcerative colitis;
adenylate-activated protein kinase/Unc-51-like kinase 1（AMPK/ULK1） pathway;
autophagy;
intestinal mucosal barrier
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2023;29(19):52-59
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo study the mechanism of Renshen Baidusan in regulating adenylate-activated protein kinase （AMPK）/Unc-51-like kinase 1 （ULK1） autophagy pathway to inhibit mucosal barrier damage in the mouse model of ulcerative colitis （UC）. MethodSixty SD rats were randomized into normal， model， sulfasalazine enteric-coated tablets （0.312 5 g·kg-1， western medicine）， and high-， medium-， and low-dose （31.2， 15.6， 7.8 g·kg-1， respectively） Renshen Baidusan groups. The UC model was induced by 2，4，6-trinitrobenzenesulfonic acid （TNBS）/50% ethanol. The drugs were administrated by gavage for 2 weeks， and then the histopathological changes of the colon were examined. Real-time quantitative polymerase chain reaction was conducted to measure the mRNA level of AMP-activated protein kinase subunit alpha （AMPKα）. Western blot was employed to determine the protein levels of closure protein （Occludin）， compact linking protein-2 （Claudin-2）， autophagy marker p62， microtubule-associated protein 1 light chain 3B （LC3B）， phosphorylated AMPK （p-AMPK）， and phosphorylated ULK1 （p-ULK1）. ResultCompared with the normal group， the model group showed increased colon injury score （P<0.05）， down-regulated mRNA level of AMPKα （P<0.05） and protein levels of p-AMPK， p-ULK1， and Occludin， decreased LC3Ⅱ/Ⅰ ratio （P<0.05）， and up-regulated protein levels of p62 and Claudin-2 （P<0.05）. Compared with the model group， all the doses of Renshen Baidusan lowered the colon injury score， up-regulated the mRNA level of AMPKα and the protein levels of p-AMPK， p-ULK1， and Occluding， increased LC3Ⅱ/Ⅰ ratio， and down-regulated the protein levels of p62 and Claudin-2. Moreover， the medium-dose group showed a significant intervention effect （P<0.05）. ConclusionRenshen Baidusan can protect the intestinal mucosal barrier from damage， and the medium dose showed the best efficacy. It may activate the AMPK/ULK1 pathway to accelerate the transformation of LC3Ⅰ to LC3Ⅱ and promote the degradation of p62， so as to improve the function of Occludin and Claudin-2 and repair the mechanical damage of the intestinal barrier.
