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Hewei Jiangni granule alleviates visceral hypersensitivity in a rat model of non-erosive reflux disease via transient receptor potential channel signaling
Institution:1. Graduate School of Beijing University of Chinese Medicine, Beijing, 100029, China;2. Department of Gastroenterology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, 100078, China;3. Department of Pharmacotherapy and Oriental Medicine, School of Pharmacy, Hyogo University of Health Sciences, Hyogo, 650-8530, Japan;4. School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 102488, China
Abstract:ObjectiveTo uncover the underlying mechanism of Hewei Jiangni granule (HWJNG) on non-erosive reflux disease (NERD) treatment by examining histological changes, gastrointestinal neurochemicals release and visceral hypersensitivity-related receptor expression in NERD model rats.MethodsA NERD rat model was established via a combination of basal sensitization and acid perfusion. HWJNG treatments at different doses were then administered. Pathological changes to tissues, mast cell (MC) activation, serum levels of esophageal visceral hypersensitivity-related neurochemicals, and transient receptor potential (TRP) receptor mRNA and protein levels were investigated.ResultsCompared with the control group, the expression of tryptase in MCs, the changes of intercellular space, and the serum levels of substance P (SP), calcitonin gene-related peptides (CGRP) and proteinase-activated receptor 2 (PAR2) increased in the model group (all P < .05). The expression of TRP vanilloid 1 (Trpv1) mRNA decreased in esophagus and dorsal root ganglia (DRG) of the model group (P = .030 & P = .013), and the expression of TRP melastatin channel subfamily member 8 (Trpm8) mRNA decreased in the esophagus of model group (P < .01). The level of esophageal TRPV1 protein increased in the model group (P < .01) and the level of TRPM8 protein decreased in esophagus and DRG of the model group (both P < .05). Compared with the model group, the serum levels of SP, CGRP, and PAR2 in the medium-dose HWJNG group showed significant decreases (all P < .05). The expression of Trpv1 mRNA in esophagus and DRG of the HWJNG groups and the Omeprazole group remarkably decreased (all P < .05), as was the expression of Trpm8 mRNA in esophagus of the HWJNG groups (all P < .05).ConclusionHWJNG alleviated visceral hypersensitivity in NERD model rats by regulating TRP-mediated signaling. Our results indicate that HWJNG has potential as a therapeutic agent for NERD.
Keywords:Hewei jiangni granule  Non-erosive reflux disease  Esophageal visceral hypersensitivity  Transient receptor  Neurochemicals
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