The Protective Effects Of Hydrochloride Ambroxol And Recombinant Human Erythropoietin On Hyperoxia-induced Lung Injury And The Effects Of Hyperoxia On Ventilator-induced Lung Injury In Adult Rats

Objective To explore oxidative/antioxidative and inflammatory reactions, apoptosis associated protein and transforming growth factor-betal in the pathogenesis of hyperoxia-induced lung injury in adult rats; to study effects of hydrochloride ambroxol (ABX) and recombinant human erythropoietin (rHuEPO) on hyperoxia-induced lung injury (HILI); to research the effects of hyperoxia on ventilator-induced lung injury in adult rats.Methods (1) Making an adult rat model of HILI: Fifty-six rats were randomly divided into seven groups, the control group was put in the air, and other six groups were put into the oxygen chamber (O₂>95%) for 24h, 48h, 72h, 96h, 96h, 96h; (2) The effects of two drugs on HILI: ABX(30mg/kg) and rHuEPO(1000u/kg) was administratored respectively through intraperitoneal injection at Oh, 24h, 48h, 72h; (3) The effects of hyperoxia on VILI: Forty-eight rats were randomly divided into four groups: group A received low tidal volume mechanical ventilation (V_T=8ml/Kg) with room air (RA), group B received the same tidal volume as group A with 100%O₂, group C received high tidal volume (V_T=40ml/Kg) with RA, group D received the same tidal volume as group C with 100%O₂; (4) Arterial blood gases were measured, then PaO₂/FiO₂ was calculated. Lung coefficient, W/D value of left lung, WBCs and neutrophils in BALF were counted. The total protein contents in BALF was calculated. TNF-a, IL-1β, and IL-6 levels in BALF and serum, MDA, SOD, and T-AOC levels in lung and serum were assayed respectively. Lung histopathology was assessed with hematoxylin and eosin stain. (5) Bax, Bcl-2, and TGF-β₁ was assayed with WB and IH.Results (1)The PaO₂/FiO₂ decreased with hyperoxia exposure. Lung coefficient, Wet-to-dry weight ratio increased, the WBCs, neutrophils, and protein contents increased. The levels of TNF-a and IL-1β in BALF and serum increased to maximum at 48h, and the levels of IL-6 in BALF and serum reached maximum at 72h. The MDA contents in lung and serum increased along with hyperoxia exposure, SOD and T-AOC activities decreased along with hyperoxia exposure. The Bax, TGF-β₁ contents in lung increased, but Bcl-2 contents decreased. Contrast with 96h group, the PaO₂/FiO₂ value of ABX, rHuEPO group increased, and lung coefficient, W/D decreased. The WBCs and neutrophils , protein contents in BALF decreased significantly. The levels of TNF-a, IL-16, and IL-6 in BALF and serum decreased. The MDA contents in lung and serum decreased and SOD, T-AOC activities increased. The Bax contents in lung decreased, but Bcl-2 contents increased. TGF-β₁ content in rHuEPO group decreased compared with 96h group; (2) After four hour ventilation, PaO₂/FiO₂ decreased significantly in group hyperoxia than RA with high tidal volume ventilation. Lung coefficient, Wet-to-dry weight ratio increased significantly. The WBCs, neutrophils, and total protein contents increased significantly. The levels of TNF-a, IL-1β, and IL-6 in BALF and serum increased. MDA levels in lung and serum increased, but activities of SOD and T-AOC decreased. Except that MDA levels increased and SOD, T-AOC activities decreased, there were no differences between group hyperoxia and RA with low tidal volume mechanical ventilation. Conclusions (1) Oxidative/antioxidative reactions, inflammatory reactions, apoptosis in lung are involved in the pathogenesis of HILI; (2) ABX, rHuEPO have protective effects on HILI respectively; (3) Hyperoxia can increase VILI in rats, but has little effects with low tidal volume mechanical ventilation.