Effect of methylprednisolone on endoplasmic reticulum stress in rats with ventilator-induced lung in-jury: the relationship with PI3K∕Akt signaling pathway
10.3760/cma.j.issn.0254-1416.2018.08.008
- VernacularTitle:甲泼尼龙对VILI大鼠肺组织内质网应激的影响:与PI3K∕Akt信号通路的关系
- Author:
Qiang YANG
1
;
Min QU
;
Shunhong MAO
;
Baojie JIAO
;
Xiangge LIU
;
Dandan SHI
;
Yali WANG
Author Information
1. 061001,沧州市中心医院麻醉科
- Keywords:
Methylprednisolone;
Respiration,artificial;
Respiratory distress syndrome,adult;
Endoplasmic reticulum;
Stress;
1-Phosphatidylinositol 3-kinase;
Protein-serine-threonine kinases
- From:
Chinese Journal of Anesthesiology
2018;38(8):925-928
- CountryChina
- Language:Chinese
-
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 spontane-ous 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 oxy-gen 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 in-creased, 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) , and no significant change was found in the indexes mentioned above in M2 and M3 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 in-hibits endoplasmic reticulum stress, thus inhibiting cell apoptosis, and the mechanism is related to activa-ting PI3K∕Akt signaling pathway in rats with VILI.