Effect of methylprednisolone on endoplasmic reticulum stress in rats with ventilator-induced lung injury: the relationship with PI3K/Akt signaling pathway

Abstract

Objective To evaluate the effect of methylprednisolone on endoplasmic reticulum stress in rats with ventilator-induced lung injury (VILI) and the relationship with phosphatidylinositol 3-kinase/serine-threonine protein kinase (PI3K/Akt) signaling pathway. Methods One hundred clean-grade male Sprague-Dawley rats, aged 4-5 months, weighing 270-320 g, were divided into 5 groups (n=20 each) using a random number table method: control group (C group), VILI group (V group) and different doses of methylprednisolone groups (M1-3 groups). Group C received no mechanical ventilation and kept spontaneous breathing for 4 h. Rats were mechanically ventilated (tidal volume 40 ml/kg, respiratory rate 15-17 breaths/min, inspiratory/expiratory ratio 1∶1, positive end-expiratory pressure 0, fraction of inspired oxygen 21% during OLV) in group V. Methylprednisolone 2, 10 and 30 mg/kg were intravenously injected at 20 min before mechanical ventilation in M1-3 groups, respectively, and the equal volume of normal saline was given in group V. Blood samples and lung tissues were taken at 4 h of ventilation for measurement of the lung permeability index (LPI) and wet/dry lung weight ratio (W/D ratio), for examination of pathological changes, and for determination of apoptosis index (AI) in lung tissues (by TUNEL), expression of Akt, phosphorylated Akt (p-Akt), glucose-regulated protein 78 (GRP78), CCAAT/enhancer-binding protein homologous protein (CHOP) and caspase-12 in lung tissues (by Western blot). Injured alveoli rate (IAR) was calculated. Results Compared with group C, the W/D ratio, LPI, IAR and AI were significantly increased, the expression of p-Akt was down-regulated, and the expression of GRP78, CHOP and caspase-12 was up-regulated in V and M1 groups (P 0.05). Compared with group V, the W/D ratio, LPI, IAR and AI were significantly decreased, p-Akt expression was up-regulated, and the expression of GRP78, CHOP and caspase-12 was down-regulated in M2 and M3 groups (P<0.05). Conclusion Methylprednisolone inhibits endoplasmic reticulum stress, thus inhibiting cell apoptosis, and the mechanism is related to activating PI3K/Akt signaling pathway in rats with VILI. Key words: Methylprednisolone; Respiration, artificial; Respiratory distress syndrome, adult; Endoplasmic reticulum; Stress; 1-Phosphatidylinositol 3-kinase; Protein-serine-threonine kinases