Basic Research

Mechanism of electroacupuncture for gastric hypersensitivity in functional dyspepsia rats rats through NGF/TrKA/TRPV1 pathway

  • Shuwen JIN ,
  • Wei LIU ,
  • Jiabao LIU ,
  • Jianchao FAN ,
  • Yongli HAN ,
  • Li ZHOU ,
  • Paidi XU ,
  • Hongxing. ZHANG
Expand
  • *.College of Acupuncture and Orthopaedics,Hubei University of Chinese Medicine,Wuhan 430061,China

Received date: 2023-02-08

  Online published: 2023-12-11

Abstract

Objective To explore the effect and mechanism of electroacupuncture (EA) on gastric hypersensitivity in rats with functional dyspepsia (FD). Methods Rats were randomly divided into blank group, model group, EA group, inhibitor group and EA+inhibitor group. The blank group was not subjected to special treatment, and the model group, EA group, inhibitor group, and EA+inhibitor group were modeled using a multi factor stimulation method. After the modeling, the model group was given routine feeding, the EA group and the EA+inhibitor group were treated with daily electroacupuncture at Zusanli, and the inhibitor group and the EA+ inhibitor group were treated with daily intraperitoneal injection of anti-nerve growth factor(NGF). Gastric hypersensitivity and gastric compliance were detected by intragastric balloon implantation, the degree of mast cell activation were observed by methylamine blue staining, the localization expression of gastric transient receptor potential vanillin subtype 1(TRPV1) was detected by immunohistochemistry, the expression of gastric NGF/tropomyosin receptor kinase (TrkA)/TRPV1 protein was detected by Western blot, and the content of gastric calcitonin gene-related peptide (CGRP) was detected by enzyme-linked immunosorbent assay. Results Compared with the blank group, the weight of the model group rats increased slowly, gastric sensitivity increased, compliance decreased, the number of gastric mast cell and degranulation rate increased significantly, and the protein expression and CGRP content of NGF, TrKA, TRPV1 increased significantly. Compared with the model group, the rats in the EA group, the inhibitor group and the EA+inhibitor group gained weight, improved gastric hypersensitivity and compliance significantly, reduced the number and activation of mast cell significantly, and reduced gastric NGF/TrKA/TRPV1 protein expression and CGRP content significantly. Compared with the EA group and the inhibitor group, the expression of NGF/TrKA/TRPV1 protein and CGRP content in the stomach of the EA+inhibitor group were further reduced, and the difference was statistically significant. Conclusion EA may relieve the gastric hypersensitivity of FD rats by regulating the NGF/TrKA/TRPV1 pathway activated by mast cells.

Cite this article

Shuwen JIN , Wei LIU , Jiabao LIU , Jianchao FAN , Yongli HAN , Li ZHOU , Paidi XU , Hongxing. ZHANG . Mechanism of electroacupuncture for gastric hypersensitivity in functional dyspepsia rats rats through NGF/TrKA/TRPV1 pathway[J]. The Journal of Practical Medicine, 2023 , 39(22) : 2928 -2933 . DOI: 10.3969/j.issn.1006-5725.2023.22.012

References

1 FORD A C, MAHADEVA S, CARBONE M F,et al. Functional dyspepsia[J]. Lancet, 2020, 396(10263):1689-1702.
2 WAUTERS L, TALLEY N J, WALKER M M,et al. Novel concepts in the pathophysiology and treatment of functional dyspepsia[J]. Gut,2020,69(3):591-600.
3 RUIZ-CANTERO M C, CORTéS-MONTERO E, JAIN A,et al. The sigma-1 receptor curtails endogenous opioid analgesia during sensitization of TRPV1 nociceptors[J]. Br J Pharmacol,2023,180(8):1148-1167.
4 LI W T, LUO Q Q, WANG B,et al. Bile acids induce visceral hypersensitivity via mucosal mast cell-to-nociceptor signaling that involves the farnesoid X receptor/nerve growth factor/transient receptor potential vanilloid 1 axis[J]. FASEB J,2019,33(2): 2435-2450.
5 TAN X, PEI W J, XIE C,et al. Tongxie Anchang Decoction Relieves Visceral Hypersensitivity in Diarrhea-Predominant Irritable Bowel Syndrome Rats by Regulating the NGF/TrkA Signaling Pathway[J]. Evid Based Complement Alternat Med,2021. doi:10.1155/2021/6679348 .
6 DEFAYE M, ABDULLAH N S, IFTINCA M,et al. Gut-innervating TRPV1+ Neurons Drive Chronic Visceral Pain via Microglial P2Y12 Receptor[J]. Cell Mol Gastroenterol Hepatol, 2022,13(4):977-999.
7 JI R, WANG P, KOU G J. Impaired gastric mucosal integrity identified by confocal endomicroscopy in Helicobacter pylori-negative functional dyspepsia[J]. Neurogastroenterol Motil, 2020,32(1):e13719.
8 CHEUNG C K Y, LAN L L, KYAW M,et al. Up-regulation of transient receptor potential vanilloid (TRPV) and down-regulation of brain derived neurotrophic factor (BDNF) expression in patients with functional dyspepsia (FD) [J]. Neurogastroenterol Motil,2018,30(2). doi:10.1111/nmo.13176 .
9 范建超,徐派的,韩永丽,等. 电针足三里对功能性消化不良模型大鼠内脏高敏感性的影响[J]. 中国组织工程研究,2022,26(5): 695-700.
10 HAN Y L, PENG X M, ZHANG H X,et al. Electroacupuncture Regulates TRPV1 through PAR2/PKC Pathway to Alleviate Visceral Hypersensitivity in FD Rats[J]. Evid Based Complement Alternat Med,2021, 2021:1975228.
11 WONG H L X, QIN H Y, TSANG S W,et al. Early life stress disrupts intestinal homeostasis via NGF-TrkA signaling[J]. Nat Commun,2019,10(1):1745.
12 YE F, LIU Y, LI S Y,et al. Sacral nerve stimulation increases gastric accommodation in rats: a spinal afferent and vagal efferent pathway[J]. Am J Physiol Gastrointest Liver Physiol,2020,318(3):G574-G581.
13 ZOU X, WANG Y, WANG Y H,et al. Paeoniflorin Alleviates Abnormalities in Rats with Functional Dyspepsia by Stimulating the Release of Acetylcholine[J]. Drug Des Devel Ther,2020,22(14):5623-5632.
14 毛广通,苗蓓,王德广. 超极化激活环核苷酸门控离子通道2在内脏高敏感性大鼠视上核的表达及作用[J]. 实用医学杂志,2021,37(4):434-440.
15 CHEN F, YANG J, ZHANG H,et al. The role of amygdala neuropsin/serpinb6 pathway in the regulation of gastric hypersensitivity and anxiety by electroacupuncture[J]. J Dig Dis,2022,23(3):149-156.
16 吕咪,张坤漓,史中斐,等. 结合罗马Ⅳ标准探讨功能性消化不良、肠易激综合征重叠的现状[J]. 实用医学杂志,2021,37(9):1213-1216.
17 董佳梓,荣培晶,马铁明,等. 电针“足三里”对功能性消化不良内脏高敏感大鼠肥大细胞/瞬时受体电位香草酸亚型1通路的影响[J]. 针刺研究,2022,47(7):592-597.
18 WANG Z M, HAO M H, WU L P,et al. Mast cells disrupt the duodenal mucosal integrity:Implications for the mechanisms of barrier dysfunction in functional dyspepsia[J]. Scand J Gastroenterol, 2023, 58(5):460-470.
19 WOUTERS M M, VICARIO M, SANTOS J. The role of mast cells in functional GI disorders[J]. Gut,2016,65(1):155-168.
20 WAUTERS L, CEULEMANS M, FRINGS D,et al. Proton Pump Inhibitors Reduce Duodenal Eosinophilia,Mast Cells,and Permeability in Patients With Functional Dyspepsia[J]. Gastroenterology,2021,60(5):1521-1531.
21 CHEN Y, CHENG J F, ZHANG Y L,et al. Electroacupuncture at ST36 Relieves Visceral Hypersensitivity via the NGF/TrkA/TRPV1 Peripheral Afferent Pathway in a Rodent Model of Post-Inflammation Rectal Hypersensitivit[J]. J Inflamm Res,2021,14:325-339.
22 李娟娟. EGC-NGF在FD脾虚证中的作用及香砂六君子方的疗效机制研究[D]. 北京: 北京中医药大学,2020.
23 华璐,郭杨,马丽,等. 普瑞巴林可通过抑制TRPV1以缓解神经病理性疼痛[J]. 实用医学杂志,2020,36(6):729-734.
Outlines

/