LIU Mengya,CHENG Yingxia,BAI Min,et al.Mechanism of Xiangsha Liujunzi Tang in Regulation of RhoA/ROCK2/MYPT1 Pathway to Improve Gastric Motility in Rats with Functional Dyspepsia[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(04):1-8.
LIU Mengya,CHENG Yingxia,BAI Min,et al.Mechanism of Xiangsha Liujunzi Tang in Regulation of RhoA/ROCK2/MYPT1 Pathway to Improve Gastric Motility in Rats with Functional Dyspepsia[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(04):1-8. DOI: 10.13422/j.cnki.syfjx.20221804.
Mechanism of Xiangsha Liujunzi Tang in Regulation of RhoA/ROCK2/MYPT1 Pathway to Improve Gastric Motility in Rats with Functional Dyspepsia
To explore the intervention mechanism of Xiangsha Liujunzi Tang in rats with functional dyspepsia (FD) based on the Ras homolog gene family member A (RhoA)/Rho-associated coiled-coil containing protein kinase 2 (ROCK2)/Myosin phosphatase target Subunit 1 (MYPT1) pathway.
Method
2
Sixty male SD suckling rats in SPF grades were randomly divided into blank group (
n
=10) and model group (
n
=50). The comprehensive modeling method (gavage administration of iodoacetamide+exhaustion of swimming+disturbance of hunger and satiety) was used to replicate the rat model of FD. After successful replication of the model, the rats in the model group were randomly divided into model group, mosapride group, and high, middle, and low-dose Xiangsha Liujunzi Tang groups, with 10 rats in each group. Rats in the blank group and model group were given 10 mL kg
-1
·d
-1
normal saline, those in the mosapride group were given 1.35 mg·kg
-1
·d
-1
mosapride, and those in the high, middle, and low-dose Xiangsha Liujunzi Tang groups were given 12, 6, and 3 g·kg
-1
·d
-1
Xiangsha Liujunzi Tang, respectively. The intervention lasted 14 days. The general living conditions of rats were observed before and after modeling and administration, and the 3-hour food intake and body mass of rats were measured. After intervention, the intestinal propulsion rate of rats was measured, and the pathological changes in the gastric tissue were observed by hematoxylin-eosin (HE) staining. The content of choline acetyl transferase (ChAT) and vasoactive intestinal peptide (VIP) in the medulla oblongata and gastric tissue homogenate was determined by enzyme-linked immunosorbent assay (ELISA), the distribution of adenosine triphosphate (ATP) enzyme in gastric antrum smooth muscle was observed by frozen section staining, and the protein expression levels of RhoA, ROCK2, and phosphorylated-myosin phosphatase target subunit 1 (p-MYPT1) in the gastric tissue were detected by Western blot.
Result
2
Compared with the blank group, the model group had withered hair, lazy movement, slow action, poor general living condition, lower 3-hour food intake, body mass, and lower intestinal propulsion rate (
P
<
0.05), whereas no obvious abnormality in gastric histopathology. In the model group, the content of ChAT in the medulla oblongata and gastric tissue decreased, the content of VIP in gastric tissue increased, the distribution of ATP enzyme in gastric antrum smooth muscle decreased significantly, and the protein expression levels of RhoA, ROCK2, and p-MYPT1 in the gastric tissue decreased significantly (
P
<
0.05). As compared with the model group, the general living condition of rats in each intervention group was significantly improved, and the 3-hour food intake, body mass, and intestinal propulsion rate were significantly increased (
P
<
0.05). There was no significant difference in gastric pathology in the intervention groups. The content of ChAT in the medulla oblongata and gastric tissue increased significantly, the content of VIP in the gastric tissue decreased, the distribution of ATP enzyme in gastric antrum smooth muscle increased significantly, and the protein expression levels of RhoA, ROCK2, and p-MYPT1 in the gastric tissue increased significantly (
P
<
0.05). The intervention effect of Xiangsha Liujunzi Tang group on the above indexes was dose-dependent.
Conclusion
2
Xiangsha Liujunzi Tang can effectively improve the general living condition and gastric motility of rats with FD, and its specific mechanism may be related to the activation of the RhoA/ROCK2/MYPT1 pathway in the gastric tissue to regulate smooth muscle relaxation and contraction and promote gastric motility.
关键词
Keywords
references
HANTORO I F , SYAM A F , MUDJADDID E , et al . Factors associated with health-related quality of life in patients with functional dyspepsia [J]. Health Qual Life Outcomes , 2018 , 16 ( 1 ): 83 .
SPERBER A D , BANGDIWALA S I , DROSSMAN D A , et al . Worldwide prevalence and burden of functional gastrointestinal disorders, results of rome foundation global study [J]. Gastroenterology , 2021 , 160 ( 1 ): 99 - 114 .
ENCK P , AZPIROZ F , BOECKXSTAENS G , et al . Functional dyspepsia [J]. Nat Rev Dis Primers , 2017 , 3 : 17081 .
TALLEY N J . American Gastroenterological Association.American Gastroenterological Association medical position statement: Evaluation of dyspepsia [J]. Gastroenterology , 2005 , 129 ( 5 ): 1753 - 1755 .
YE Y , WANG X R , ZHENG Y , et al . Choosing an animal model for the study of functional dyspepsia [J]. Can J Gastroenterol Hepatol , 2018 , 2 ( 12 ): 1531958 .
ZOU X , WANG Y , WANG Y , et al . Paeoniflorin alleviates abnormalities in rats with functional dyspepsia by stimulating the release of acetylcholine [J]. Drug Des Devel Ther , 2020 , 14 : 5623 - 5632 .
Clinical Observation of Effects of Modified Xiangsha Liujunzi Tang Application on Adverse Reaction of Moderately/Highly Emetogenic Chemotherapy for Gastrointestinal Tumors
Effect and Mechanism of Xiangsha Liujunzi Tang on Lipid Deposition in Liver of ApoE-/- AS Mice by Affecting Long Noncoding RNA-HC/miR-130b and to Regulate Cholesterol Metabolism
Study on Chemical Constituents in Water Decoction of Ethyl Acetate Parts of Xiangsha Liujunzi Tang
Clinical Efficacy of Xiangsha Liujunzi Tang Combined with Acupuncture Therapy in Treatment of Syndrome of Deficiency of Spleen Qi and Stomach Qi of Functional Dyspepsia
Related Author
Zhi-qiang CHENG
Li-ya LI
Yan-ni LOU
Fei SU
Nan SONG
Si CHEN
Lian-qun JIA
Qun WANG
Related Institution
Japan Friendship Hospital
Chinese Medicine Innovation Engineering Technology Center, Liaoning Key Laboratory of Ministry of Education for Traditional Chinese Medicine (TCM) Viscera-State Theory and Applications,Liaoning University of TCM
Liaoning University of TCM
The Second Affiliated Hospital of Liaoning University of TCM
Chongqing Key Laboratory of Traditional Chinese Medicine (TCM) for Prevention and Cure of Metabolic Diseases