Mechanism of Xiangsha Liujunzi Decoction in improving autophagy in interstitial cells of Cajal of rats with functional dyspepsia by regulation of IRE1/ASK1/JNK pathway.
10.19540/j.cnki.cjcmm.20241111.705
- Author:
Ming-Kai LYU
1
;
Yong-Qiang DUAN
2
;
Jin JIN
3
;
Wen-Chao SHAO
4
;
Qi WU
4
;
Yong TIAN
3
;
Min BAI
1
;
Ying-Xia CHENG
1
Author Information
1. College of Traditional Chinese Medicine,Ningxia Medical University Yinchuan 750004,China Key Laboratory of Ningxia Ethnomedicine Modernization,Ministry of Education Yinchuan 750004,China.
2. College of Traditional Chinese Medicine,Ningxia Medical University Yinchuan 750004,China Ningxia Regional Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Regional High Incidence Disease Yinchuan 750004,China.
3. College of Traditional Chinese Medicine,Ningxia Medical University Yinchuan 750004,China.
4. Helan County Hospital of Traditional Chinese Medicine Yinchuan 750004,China.
- Publication Type:Journal Article
- Keywords:
Xiangsha Liujunzi Decoction;
autophagy;
endoplasmic reticulum stress;
functional dyspepsia;
interstitial cells of Cajal
- MeSH:
Animals;
Male;
Drugs, Chinese Herbal/administration & dosage*;
Autophagy/drug effects*;
Rats;
Rats, Sprague-Dawley;
Interstitial Cells of Cajal/metabolism*;
Dyspepsia/physiopathology*;
Protein Serine-Threonine Kinases/genetics*;
MAP Kinase Kinase Kinase 5/genetics*;
MAP Kinase Signaling System/drug effects*;
Humans;
Endoribonucleases/genetics*;
Multienzyme Complexes
- From:
China Journal of Chinese Materia Medica
2025;50(8):2237-2244
- CountryChina
- Language:Chinese
-
Abstract:
This study explored the mechanism of Xiangsha Liujunzi Decoction(XSLJZD) in the treatment of functional dyspepsia(FD) based on inositol-requiring enzyme 1(IRE1)/apoptosis signal-regulating kinase 1(ASK1)/c-Jun N-terminal kinase(JNK) pathway-mediated autophagy in interstitial cells of Cajal(ICC). Forty-eight SPF-grade male SD suckling rats were randomly divided into a blank group and a modeling group, and the integrated modeling method(iodoacetamide gavage + disturbance of hunger and satiety + swimming exhaustion) was used to replicate the FD rat model. After the model replications were successfully completed, the rats were divided into a model group, high-dose, medium-dose, and low-dose groups of XSLJZD(12, 6, and 3 g·kg~(-1)·d~(-1)), and a positive drug group(mosapride of 1.35 mg·kg~(-1)·d~(-1)), and the intervention lasted for 14 days. The gastric emptying rate and intestinal propulsion rate of rats in each group were measured. The histopathological changes in the gastric sinus tissue of rats in each group were observed by hematoxylin-eosin(HE) staining. The ultrastructure of ICC was observed by transmission electron microscopy. The immunofluorescence double staining technique was used to detect the protein expression of phospho-IRE1(p-IRE1), TNF receptor associated factors 2(TRAF2), phospho-ASK1(p-ASK1), phospho-JNK(p-JNK), p62, and Beclin1 in ICC of gastric sinus tissue of rats in each group. Western blot was used to detect the related protein expression of gastric sinus tissue of rats in each group. Compared with those in the blank group, the rats in the model group showed decreased body weight, gastric emptying rate, and intestinal propulsion rate, and transmission electron microscopy revealed damage to the endoplasmic reticulum structure and increased autophagosomes in ICC. Immunofluorescence staining revealed that the ICC of gastric sinus tissue showed a significant elevation of p-IRE1, TRAF2, p-ASK1, p-JNK, and Beclin1 proteins and a significant reduction of p62 protein. Western blot revealed that the expression levels of relevant proteins in gastric sinus tissue were consistent with those of proteins in ICC. Compared with the model group, the body weight of rats in the high-dose and medium-dose groups of XSLJZD was increased, and the gastric emptying rate and intestinal propulsion rate were increased. Transmission electron microscopy observed amelioration of structural damage to the endoplasmic reticulum of ICC and reduction of autophagosomes, and the p-IRE1, TRAF2, p-ASK1, p-JNK, and Beclin1 proteins in the ICC of gastric sinus tissue were significantly decreased. The p62 protein was significantly increased. Western blot revealed that the expression levels of relevant proteins in gastric sinus tissue were consistent with those of proteins in ICC. XSLJZD can effectively treat FD, and its specific mechanism may be related to the inhibition of the expression of molecules related to the endoplasmic reticulum stress IRE1/ASK1/JNK pathway in ICC and the improvement of autophagy to promote gastric motility in ICC.
