Role of endogenous heme oxygenase-1/carbon monoxide signaling pathway in endoplasmic reticulum stress during endotoxin-induced acute lung injury in rats
10.3760∕cma.j.issn.0254-1416.2019.06.025
- VernacularTitle:HO-1/CO信号通路在大鼠内毒素性急性肺损伤时内质网应激中的作用
- Author:
Lirong GONG
1
;
Lili WU
;
Rui MU
;
Chunhui ZONG
;
Shihan DU
;
Yanfang ZHANG
;
Jianbo YU
Author Information
1. 天津医科大学南开临床学院 天津市南开医院麻醉科 300100
- Keywords:
Heme oxygenase-1;
Carbon monoxide;
Endotoxins;
Acute lung injury;
Endo-plasmic reticulum stress
- From:
Chinese Journal of Anesthesiology
2019;39(6):734-737
- CountryChina
- Language:Chinese
-
Abstract:
Objective To evaluate the role of endogenous heme oxygenase-1/carbon monoxide ( HO-1/CO) signaling pathway in endoplasmic reticulum stress during endotoxin-induced acute lung injury ( ALI) in rats. Methods Forty healthy clean-grade male Sprague-Dawley rats, aged 8 weeks, weighing 190-210 g, were divided into 4 groups ( n=10 each) using a random number table method: control group (group C), ALI group, ALI plus ZnPP-IX group (group AZ), and ALI plus vehicle sodium bicarbonate group ( group AV) . ALI was induced by intravenously injecting lipopolysaccharide 5 mg/kg in anesthetized rats. At 30 min before establishing the model, ZnPP-IX 10μmol/kg (diluted to 1 ml in 50 mmol/L sodium bicarbonate) was intraperitoneally injected in group AZ, and 50 mmol/L sodium bicarbonate 1 ml was intra-peritoneally injected in group AV. After injecting lipopolysaccharide for 6 h, blood samples were collected from the common carotid artery for determination of plasma CO concentration, the rats were then sacrificed, and lungs were removed for microscopic examination of the pathological changes which were scored and for determination of CO level, wet to dry weight ratio ( W/D ratio) , cell apoptosis ( by TUNEL) , and expres-sion of heme oxygenase-1 ( HO-1) , glucose-regulated protein 78 ( GRP78) , phosphorylated protein kinase R-like endoplasmie reticulum kinase (p-PERK), phosphorylated eukaryotic translation initiation factor 2 alpha ( p-elF2 ) , CCAAT/enhancer-binding protein homologous protein ( CHOP ) and caspase-12 in lung tissues ( by Western blot) . Apoptosis index ( AI) was calculated. Results Compared with group C, the lung injury scores, W/D ratio, AI and CO levels in plasma and lung tissues were significantly increased, and the expression of HO-1, GRP78, p-PERK, p-elF2, CHOP and caspase-12 was up-regulated in the other three groups ( P＜0. 05) . Compared with group ALI, lung injury scores, W/D ratio and AI were sig-nificantly increased, CO levels in plasma and lung tissues were decreased, the expression of HO-1 was down-regulated, and the expression of GRP78, p-PERK, p-elF2, CHOP and caspase-12 was up-regula-ted in group AZ (P＜0. 05), and no significant change was found in the parameters mentioned above in group AV ( P＞0. 05) . Conclusion HO-1/CO signaling pathway produces endogenous protection possibly through inhibiting endoplasmic reticulum stress during endotoxin-induced ALI in rats.
