Shugan Jiangni Hewei Granule regulates synaptic plasticity in central sensitization via NGF/TrkA Signaling Pathways in psychological stress rats with nonerosive reflux disease

Abstract Objective. We sought to investigate the mechanism of visceral hypersensitivity improvement of Shugan Jiangni Hewei Granules (SJHG) treatment of non-erosive reflux disease (NERD) and provide an experimental basis for its clinical application. Methods. Fifty healthy male Sprague-Dawley (SD) rats were divided into 5 groups, with 10 rats in each group, including normal group (healthy rats), model group (model rats without any treatment), SJHG group (model rats with SJHG treatment), Omeprazole group (model rats with Omeprazole treatment), and k252a group (model rats treated with 100μmol/kg NGF/TrkA pathway inhibitor).The esophageal mucosa and synaptic vesicles in spinal cord were observed by EMT, NGF, TrkA, PSD95, and GAP43 proteins expression in spinal cord were detected by western blot, and GluA1 protein expression in spinal cord was detected by immunohistochemistry among the normal group, model group, SJHG group and Omeprazole group, PSD95 protein expression in spinal cord was detected by immunofluorescence. Results. In the model group, the intercellular spaces of epithelia of esophageal mucosa widened, and the synaptic vesicles in spinal cord increased compared with the normal group. NGF amd TrkA proteins of model group in the spinal cord were significantly increased compared with the normal group (P<0.01), After the treatment of SJHG or Omeprazole or k252a, the expression of NGF amd TrkA were decreased compared with the model rats. (P<0.01). GAP43, PSD95 proeins of model group in the spinal cord were higher than that of the normal group.(P<0.01). Compared with the normal group, the expression of NGF increased (P<0.05), but no significant difference of TrkA and CREB mRNA expression. The content of GluA1 in spinal cord of rats in normal group was low. According to the integrated optical density (IOD), GluA1 protein in the model group was higher than that in the normal group (P<0.01). The expression of GluA1 of both the SJHG group and the Omeprazole group decreased signifcantly (P<0.01).Conclusions. SJHG can ameliorate visceral hypersensitivity and decrease central hypersensitivity in mental stress rats with non-erosive reflux disease, which is partially due to the regulation of NGF/TrkA signaling pathways. Psychological factor is also an important cause of visceral hypersensitivity. These findings provided a new target for Traditional Chinese medicine treatment of NERD to improve the hypersensitivity of esophageal viscera.