Role and Mechanism of TRPV1 and NaV1.8 in Esophageal Hypersensitivity
10.3969/j.issn.1008-7125.2023.11.001
- VernacularTitle:TRPV1和NaV1.8在食管高敏感中的作用及其机制研究
- Author:
Baixin WU
1
,
2
;
Cirenyuzhen
;
Shuai PENG
;
Zunan WU
;
Yuling ZHANG
;
Xiaoyun YU
;
Lei SHEN
Author Information
1. 武汉大学人民医院消化内科(430060)
2. 消化系统疾病湖北省重点实验室
- Keywords:
Gastroesophageal Reflux Disease;
Esophageal Hypersensitivity;
TRPV1;
NaV1.8;
Nodose Ganglion;
Jugular Ganglion
- From:
Chinese Journal of Gastroenterology
2023;28(11):641-649
- CountryChina
- Language:Chinese
-
Abstract:
Background:Gastroesophageal reflux disease(GERD)is a common digestive system disease with typical symptoms of acid reflux and heartburn,and high sensitivity of esophagus is an important cause of heartburn and other symptoms.TRPV1 and NaV1.8 may play an important role in the regulation of esophageal hypersensitivity,and the specific mechanism is not yet clear.Aims:To detect the expression levels of TRPV1 and NaV1.8 in esophageal sensory neuron in GERD state and explore their role in mediating esophageal hypersensitivity.Methods:Twelve guinea pigs were randomly divided into control group and GERD group.The GERD guinea pig model was established by drinking hydrochloric-pepsinogen acid water,the body mass of guinea pigs was monitored,the esophageal inflammatory histological score was performed,and the successful construction of the GERD model was verified by measuring the expression indicators of inflammatory factors.The heart rate variability method was used to detect whether the guinea pigs were in the state of visceral hypersensitivity.The expression and co-expression of TRPV1 and NaV1.8 in esophagus,nodular ganglion and jugular ganglion were detected by immunofluorescence,Western blot and real-time fluorescence quantification.Results:Compared with the control group,the score of esophageal inflammatory histology in GERD group was much higher than that in the control group(0.96 vs.0.22).The contents of esophageal inflammatory factors interleukin(IL)-1β,IL-6 and tumor necrosis factor(TNF)-α were significantly increased(P<0.05),while the contents of anti-inflammatory factor IL-10 were decreased(P<0.05).The index of heart rate variability,low frequency to high frequency ratio(LF/HF)had no significant difference between the GERD group and the control group(P>0.05),and the LF/HF in the GERD group was higher than that in the control group after the molding(P<0.05).In esophagus and jugular,the expression levels of TRPV1 and NaV1.8 in GERD group were increased and the co-expression levels were up-regulated(P<0.05),while the expression levels in nodose were not significantly changed(P>0.05).Conclusions:In the case of esophageal acid exposure,the expression levels of TRPV1 and NaV1.8 in the esophageal mucosal epithelium increased,while the expression levels in jugular ganglion were up-regulated,thus promoting the transmission of pain signals in the vagus nerve pathway,and ultimately leading to the occurrence of esophageal hypersensitivity.
