Abstract

Objective To observe the effect of methylprednisolone pretreatment on mechanical ventilation-related lung injury in rats, and to explore its mechanism. Methods Eighty SD rats were randomly divided into four groups: control group (group C), mechanical ventilation group (group V), methylprednisolone group (group Mp), JNK inhibitor SP600125 + methylprednisolone group (group SMp). Group C does not mechanically ventilate and naturally breathes air.Group V: high tidal volume mechanical ventilation for 4h, inhalation of oxygen concentration of 21%.SP600125 30 μg/100 g subcutaneous injection was given 30 min before mechanical ventilation in group SMp.Group Mp and group SMp: 10 mg/kg of methylprednisolone was injected intravenously 10 min before mechanical ventilation.Femoral arterial blood samples were collected immediately after intubation, mechanical ventilation at 1, 2, and 4 h, arterial blood gas analysis was performed, PaO2 was recorded, and oxygenation index (OI) was calculated.Rats were sacrificed 4 hours after mechanical ventilation, and alveolar bronchial lavage fluid (BALF) was recovered to detect the concentration of total protein, TNF-α and macrophage inflammatory protein-2 (MIP-2) in BALF.The lung permeability index (LPI) was measured, and the left lower lobe was taken to determine the lung wet/dry weight (W/D) ratio.The activity of myeloperoxidase (MPO) in lung tissue was measured, and the expression level of intercellular adhesion molecule-1 (ICAM-1) was examined.The expression levels of JNK and p-JNK were detected by Western blot.The expression level of JNK mRNA was detected by RT-PCR.The pathological findings of lung tissue were observed under light microscope to determine the alveolar damage rate (AIR). Results Compared with group C, OI decreased, W/D ratio, LPI, AIR, AI, MPO, ICAM-1 increased.Increased concentration of total protein, TNF-α and MIP-2 in BALF, and p-JNK and JNK mRNA expression were up-regulated in group SMp of group V (P 0.05). Compared with group V, in group Mp and group SMp, OI increased, W/D ratio, LPI, AIR, AI, MPO, ICAM-1 decreased.The concentration of total protein, TNF-α and MIP-2 in BALF is reduced, and p-JNK and JNK mRNA expression were down-regulated, the difference was statistically significant (P<0.05). Compared with the group Mp, in the group SMp, the OI decreased, the W/D ratio, LPI, AIR, AI, MPO, ICAM-1 increased.The concentration of total protein, TNF-α and MIP-2 in BALF is increased, and the expression of p-JNK and JNK mRNA were up-regulated (P<0.05). Compared with group C, the pathological damage of lung tissue in group V and group SMp was heavier.Compared with group V, the pathological damage of lung tissue in group Mp was alleviated.The pathological damage of group SMp was between group V and group Mp. Conclusions Methylprednisolone can alleviate the mechanical ventilation-related lung injury in rats, and its mechanism is related to the inhibition of JNK phosphorylation in lung tissue. Key words: Methylprednisolone; Respiratory, artifical; JNK mitogen-activated protein kinases; Lung injury

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