[Effects of mechanical ventilation on the expression of Toll like receptor 4 in rat's alveolar macrophages].

Objective: To investigate the effects of mechanical ventilation on Toll like receptor 4 (TLR4) in rat's alveolar macrophages (AM).

Methods: Eighteen clean grade adult male SD rats weighting 230-240 g were randomly divided into three groups (n=6): autonomous breathing group(R group), small tidal volume (V(T)) mechanical ventilation group (M group, V(T)=6 ml/kg) and large V(T) mechanical ventilation group (N group, V(T)=40 ml/kg). The animals were anesthetized with intraperitoneal 20% urethane 8 ml/kg, tracheostomized and mechanically ventilated [inhalation: exhalation (I:E)=1:1, with positive end-expiratory pressure (PEEP)=0, fraction of inspired oxygen (FiO(2))=0.21]. The respiratory rate was adjusted, and end-tidal carbon dioxide partial pressure (P(ET)CO(2)) was maintained at 35-45 mm Hg (1 mm Hg=0.133 kPa). Arterial blood samples were taken for blood gas analysis at the beginning of the experiment and 1, 2 and 3 hours after the experiment. The experiment was terminated, and pathomorphology score, pulmonary tissue wet/dry (W/D) weight ratio, white blood cells count (WBC) in bronchoalveolar lavage fluid (BALF) were determined at 3 hours. The rats were sacrificed by bloodletting after experiment. Then the rats' BALF and pulmonary albumin permeability (PAP) were determined. The expression of AM TLR4 mRNA was assessed by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). AM TLR4 protein expression was determined by immunohistochemistry.

Results: Over ventilation, elevated pH and lower partial pressure of carbon dioxide in arterial blood (PaCO(2)) were observed in N group at 1 hour, and other indexes were normal. The pulmonary pathomorphology score, pulmonary W/D weight ratio, WBC in BALF, PAP, and the mRNA expression of TLR4 and the protein of TLR4 in AM in the N group were greatly increased as compared with the R group (all P<0.01), while they were not significantly changed in the M group (all P>0.05).

Conclusion: Large V(T) mechanical ventilation induced injury of lungs and up-regulated TLR4 expression in rat's AM. Small V(T) mechanical ventilation avoided above-mentioned changes.