Effects of cholinergic anti-inflammatory pathway on ventilator-induced lung injury in rats

Abstract

To investigate the effects of cholinergic anti-inflammatory pathway on ventilator-induced lung injury (VILI) in rats. Thirty-six healthy Sprague-Dawley (SD) rats were randomly divided into three groups: control group, in which rats did not receive ventilation; high-tidal volume (HVT) ventilation group; nicotine treatment (HVT+nicotine) group, in which rats received intraperitoneal injection of nicotine (2 mg/kg) 10 minutes before HVT ventilation; equal amount of normal saline was given to rats in other two groups. A rat model of VILI was reproduced by volume-controlled mechanical ventilation with HVT. Hemodynamic parameters were measured throughout the study period. Arterial blood gases were measured every 1 hour. After maintaining ventilation for 2 hours, rats were sacrificed and lung tissue specimens were harvested. Lung wet-dry weight ratio (W/D) and myeloperoxidase (MPO) activity were measured. Interleukin-8 (IL-8) level in bronchoalveolar lavage fluid (BALF) and intercellular adhesion molecule-1 (ICAM-1) level in lung tissue homogenate were measured by enzyme-linked immunosorbent assay (ELISA), respectively. After hematoxylin and eosin (HE) staining, pathological examination of lung tissue was performed, and diffuse alveolar damage (DAD) score was estimated. Mean pH of arterial blood in HVT group and HVT+nicotine group tended to be higher than the baseline value during the ventilation. Mean partial pressure of oxygen in arterial blood (PaO2), mean partial pressure of carbon dioxide in arterial blood (PaCO2), and mean arterial pressure (MAP) in HVT group and HVT+nicotine group were lower than baseline value during the ventilation. Mean PaO2 (mm Hg, 1 mm Hg=0.133 kPa) in HVT+nicotine group was significantly higher than that in HVT group after 2 hours of ventilation (85+/-4 vs. 76+/-3, P<0.05). Mean W/D ratio and mean MPO activity in HVT group were significantly higher than those in control group [W/D ratio: 5.66+/-0.33 vs. 4.53+/-0.21, P<0.01; MPO (U/g): 1.73+/-0.50 vs. 0.89+/-0.17, P<0.05]. Mean W/D ratio (5.02+/-0.37) and mean MPO activity (1.11+/-0.33) in HVT+nicotine group were significantly lower than those in HVT group (both P<0.05). Compared with control group, DAD scores in HVT group and HVT+nicotine group (10.40+/-1.85, 7.90+/-1.67 vs. 1.60+/-1.20), IL-8 concentration (ng/L: 1 625.3+/-271.7, 965.5+/-310.5 vs. 428.5+/-120.6) and ICAM-1 concentration (microg/L: 589.4+/-87.5, 452.5+/-89.3 vs. 247.5+/-73.7) were significantly higher (all P<0.01). But DAD score, IL-8 concentration, ICAM-1 concentration in HVT+nicotine group were significantly lower than those in HVT group (P<0.05 or P<0.01). Activation of cholinergic anti-inflammatory pathway can protect the lung against VILI by suppressing IL-8 and ICAM-1 expression, inhibiting neutrophil aggregation and infiltration.