The Role Of Neurokinin-1 Receptor In Gastroesophageal Reflux Model Of Guinea Pigs With The Increase Of Cough Reflex Sensitivity

[Objection] To explore the relationships between cough reflex sensitivity and the neurokinin-1 receptor expression in lung and dorsal vagal complex of gastroesophageal reflux model.[Methods] Healthy male Hartly guinea pigs that cough reflex sensitivity are normal were randomized into five groups, control group, physiological saline group, model group, model+BTX-A group and model+NS group. Use the method that esophageal intubation and perfused HC1 continuous 15 days to establish a guinea pig model of GERD. Use or not use botulinum toxin-A, measured citric acid-induced cough times and latency in the end of building model and observed neurokinin-1 receptor expressions in the lung and dorsal vagal complex by immunohistochemical staining and/or western blot.[Results] (1) Compared with the control groups, the cough times of model group was significantly increased and the cough latency significantly shorter (51.17±10.19 vs29.50± 13.40,8.24±4.73 vs 38.17±9.91, P<0.05). Injectd botulinum toxin-A into airway, the cough times were significantly decreased(23.33±7.53 vs 51.17±10.19, P<0.05), but the cough latency was no significant difference (11.76±3.29 vs 8.24±4.73, P>0.05) compared with the model group. (2) The neurokinin-1 receptor immunohistochemical staining results from the lung tissue and dorsal vagal complex suggested that the numbers of neurokinin-1 receptor-immunoreactive substances were significantly increased, with a stronger response in the model group compared with the control groups(108.48±25.71 vs38.54±17.62,4.99±0.44 vs1.96±0.16, P<0.05). After used the botulinum toxin-A, neurokinin-1 receptor-immunoreactive substances were decreased significantly compared with model group(21.59±13.45 vs 108.48±25.71,1.32±0.11vs4.99± 0.44, P<0.05). (3) In the model groups, the expression of neurokinin-1 receptor protein in dorsal vagal complex was increased compared with control groups (1.00±0.43 vs 0.46±0.34, P<0.05). Pretreated botulinum toxin-A, the expression of ncurokinin-1 receptor protein lever was decreased significantly compare with model group (0.49±0.33 vs 1.00±0.43, P<0.05).[Conclusion]Increased of cough time and shortened cough latency suggested that GERD inhanced the cough reflex sensitivity in guinea pigs and it can be blocking by injectable botulinum toxin-A into airway. And the expression of neurokinin-1 receptor may play an important role in the gastroesophageal reflux model of guinea pigs with the increase of cough reflex sensitivity.