Effect of Coptisine on PI3K/Akt/mTOR Signaling Pathway in Chronic Atrophic Gastritis Rats
10.13422/j.cnki.syfjx.20240823
- VernacularTitle:黄连碱对慢性萎缩性胃炎大鼠PI3K/Akt/mTOR信号通路的影响
- Author:
Jie WANG
1
;
Pengli DU
1
;
Jiaqi DONG
2
;
Yuewei YANG
2
;
Yunxiao GAO
2
;
Hongyu MA
3
;
Xuemei JIA
1
;
Yuxi GUO
2
;
Bolin LI
1
;
Qian YANG
1
Author Information
1. Hebei Key Laboratory of Turbidity Toxin Syndrome， Key Laboratory of Integrated Chinese and Western Medicine for Gastroenterology Research （Hebei）， Hebei Provincial Hospital of Traditional Chinese Medicine， Shijiazhuang 050011， China
2. Hebei University of Chinese Medicine， Shijiazhuang 050091， China
3. Hebei General Hospital， Shijiazhuang 050051， China
- Publication Type:Journal Article
- Keywords:
chronic atrophic gastritis;
coptisine;
phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR）;
inflammation;
pepsinogen
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2024;30(18):117-124
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the therapeutic effect and mechanism of coptisine on chronic atrophic gastritis （CAG） in rats based on the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway. MethodA CAG rat model was induced by multiple factors， including sodium salicylate， N-methyl-N′-nitro-N-nitrosoguanidine （MNNG）， and irregular feeding. The successfully modeled rats were randomly divided into the model group， folic acid group， and high- and low-dose coptisine groups. The high- and low-dose coptisine groups were given coptisine （50， 10 mg·kg-1， respectively）， and the folic acid group was given folic acid at 2 mg·kg-1 for 60 days. The pathological changes were detected by hematoxylin-eosin （HE） staining. The ultrastructure of gastric mucosal cells was observed by electron microscopy. Serum pepsinogen Ⅰ （PGⅠ）， pepsinogen Ⅱ （PGⅡ）， and PGⅠ/PGⅡ ratio （PGR） were detected by immunoturbidimetry. Serum gastrin-17 （G-17） level was detected by radioimmunoassay. The content of interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） in serum of rats was detected by enzyme-linked immunosorbent assay （ELSIA）. Western blot analysis was used to detect the expression levels of TGF-β1， PI3K， phosphorylated-Akt （p-Akt）， mTOR， and phosphatase and tensin homolog deleted on chromosome 10 （PTEN） in gastric mucosa. The mRNA levels of TGF-β1， PI3K， Akt， mTOR， PTEN， microtubule-associated protein light chain 3Ⅱ （LC3Ⅱ）， and Beclin-1 were detected by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the normal group， the model group showed atrophy and reduced number of intrinsic glands in the gastric mucosal tissues， as well as inflammatory cell infiltration. The ultrastructure of gastric mucosal cells in the model group displayed nuclear condensation， reduced and swollen mitochondria， and abnormal structure. The serum levels of G-17， PGⅠ， PGR， and the protein and mRNA levels of PTEN in gastric tissues were significantly lower in the model group （P<0.01）， while serum levels of IL-6， IL-1β， TNF-α， and the protein and mRNA levels of TGF-β1， PI3K， Akt， and mTOR in gastric tissues were significantly higher （P<0.01）. Compared with the model group， various drug intervention groups showed different degrees of improvement in pathological damage and gastric mucosal cell ultrastructure， significantly increased serum levels of G-17， PGⅠ， and PGR （P<0.05，P<0.01）， and significantly decreased levels of IL-6， IL-1β， and TNF-α （P<0.05，P<0.01）. The high-dose coptisine group significantly downregulated the protein and mRNA levels of TGF-β1， PI3K， Akt， and mTOR （P<0.05，P<0.01）. ConclusionBerberine has a therapeutic effect on CAG in rats， possibly exerting a protective effect on gastric mucosa by inhibiting inflammation and blocking the PI3K/Akt/mTOR signaling pathway.
