TRPA1Ion Channels In Vagal Afferent Nerves Contribute To Ventilator-induced Lung Injury

In order to investigate the effects of TRPA1mediatedneurogenic inflammatory reaction in the process of ventilator induced lung injury (VILI). A ventilator-induced lung injury animal model in rats was prepared, the results were described as follows:1Preparation of the ventilator-induced lung injury animal model in ratsSixtyspecific-pathogen free(SPF) Sprague-Dawley rats were assigned into3groups(n=20) randomly:group A:rats were unventilated; group B:rats were ventilated with7mL/kg tidal volume room air for four hour; group C:rats were ventilated with40mL/kg tidal volume room air for four hour. A3.5mm innerdiameterangiocatheter was inserted into the tracheaand sutured in place. Peak pressure and respirationrate were regulated to the level when a targeted tidalvolume reached7or40ml/kg. Heart rate, blood pressureand temperature were monitored continuously throughoutthe experiments.The thorax was opened, and blood wassampled by cardiac puncture. The samples of pulmonary tissue and lung lavage fluid were collected. The jugular/nodose ganglia which were near lungs were dissected and cleared of adhering connective tissue.the lung homogenate was obtained from each group. Between group A and groupB, no substantial changes in morphology were observed. But in group C the alveolar congestion, hemorrhage, infiltration of neutrophils in airspace, vessel wall and the thickness of alveolar wall were observed; the interstitial pulmonary edema and pneumorrhagia were observed too. The W/D ratio in group C was significantly higher than in the groups A and B, while no difference was found between groups A and B in rats lung tissues.We conclued that large tidal volume mechanical ventilation (40ml/kg) might cause the lung injury. And ventilation of this volume can build the model of ventilator induced lunginjury inrats. 2Effects of TRPA1mediated neurogenic inflammatory reaction in process of VILI.Sixtyspecific-pathogen free(SPF) Sprague-Dawley rats were assigned into3groups(n=20) randomly.group A:rats were unventilated; group B:rats were ventilated with7mL/kg tidal volume room air for four hour; group C:rats were ventilated with40mL/kg tidal volume room air for four hour. The lung tissue level of oxidative stress in the rat tidal volume mechanical ventilation significantly increased of a serious imbalance. Moreover, with the increase of the tidal volumeof ventilation, this trend was more pronounced. The contents of TNF-α, IL-8and the level of Substance P were significantly increased in the tidal volume ventilation groups by comparing with the vehicle group (p<0.01). But TRPA1expression was no significant difference between these groups by compared with the control of β-actin.We conclued that:Large tidal volume mechanical ventilation (40ml/kg) might cause the lung injury.; and the neurogenic inflammation is one of themechanisms of VILI, and the activating of TRPA1in vagal afferent nerves in the early inflammatory process of VILI would contribute to induce the neurogenic inflammation, and finally induced to lung injury.3Effects of TRPA1antagonist in the process of TRPA1mediated neurogenic inflammatory reaction in VILI.SD rats were randomly divided into five groups:Vehicle group (group A), low tidal volume ventilation group (group B), high tidal volume ventilation group (group C), low tidal volumeventilation+TRPA1inhibitor (group D), high tidal volume ventilation+TRPA1inhibitor (group E). Pretreatment with TRPA1inhibitor, HC-030031,reduced both the lung W/D as well as the contents of WBC and MPO in lung tissues of the hyper-ventilation group. The TRPA1antagonist could significantly reduce the inflammatory response and the generation of reactive oxygen species (ROS), and improve SOD activity in lung tissues. Moreover, the TRPA1antagonist extremely inhibited the production of inflammatory factors such as IL-8and TNF-a in lung tissues especially on the high tidal volume ventilation groups. TRPA1inhibitor could inhibit the expression of substance P in vagal nerve afferent.But the TRPA1was expressed in the vagalnervous ganglia, and there was no significant difference between these groups by compared with the control of β-actin. It was indicated that TRPA1may involve in the pathophysiological process of VILI, and TRPA1antagonist could help to improve theinflammatory response.