Critical Care Medicine
Role of Nrf2/HO-1 signaling pathway in bone marrow mesenchymal stem cells-induced reduction of endotoxin-induced acute lung injury in rats
Qun Lin, Yiqing Guo, Xiaohua Lin, Feng Chen, Jun Ke, Lihua Lei
Published 2019-03-20
Cite as Chin J Anesthesiol, 2019, 39(3): 381-384. DOI: 10.3760/cma.j.issn.0254-1416.2019.03.033
Abstract
ObjectiveTo evaluate the role of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway in bone marrow mesenchymal stem cells (MSCs)-induced reduction of endotoxin-induced acute lung injury (ALI) in rats.
MethodsThirty-two clean-grade healthy male Sprague-Dawley rats, weighing 180-250 g, were divided into 4 groups (n=8 each) using a random number table method: control group (group C), ALI group, MSCs group and brusatol plus MSCs group (group B+ MSCs). Lipopolysaccharide 20 mg/kg was intravenously infused to establish the model of acute lung injury. Phosphate buffered saline(PBS)1 ml was intravenously infused at 1 h after establishing the model in group ALI. The equal volume of sterile saline and PBS was given instead in group C. PBS (1 ml) containing MSCs 1×106 cells was intravenously infused at 1 h after establishing the model in group MSCs. Brusatol 0.4 mg/kg was intraperitoneally injected every other day during 10 days before establishing the model, and MSCs were given at 1 h after establishing the model in group B+ MSCs. Bronchoalveolar lavage fluid (BALF) was collected and lung tissues were removed at 6 h after establishing the model. The protein concentration and neutrophil count in BALF were determined, and the wet/dry weight ratio (W/D ratio) were calculated. The pathological changes of lung tissues were observed by hematoxylin-eosin staining. The expression of Nrf2 and HO-1 by Western blot, activities of myeloperoxidase (MPO) and superoxide dismutase (SOD) and content of malondialdehyde (MDA) were determined .
ResultsCompared with group C, the W/D ratio and total cell count and protein concentration in BALF were significantly increased, the MPO activity was enhanced, the MDA content was increased, the SOD activity was weakened, and the expression of Nrf2 was up-regulated (P<0.05), and the pathological changes were accentuated in group ALI. Compared with group ALI, the W/D ratio and total cell count and protein concentration in BALF were significantly decreased, the MPO activity was weakened, the MDA content was decreased, the SOD activity was enhanced, and the expression of Nrf2 and HO-1 was up-regulated (P<0.05), and the pathological changes were significantly attenuated in group MSCs. Compared with group MSCs, the total cell count was significantly increased, the MPO activity was enhanced, the MDA content was increased, the expression of Nrf2 and HO-1 was down-regulated (P<0.05), and the pathological changes were accentuated in group B+ MSCs.
ConclusionNrf2/HO-1 signaling pathway is involved in bone marrow MSCs-induced reduction of endotoxin-induced acute lung injury in rats.
Key words:
NF-E2 related factor 2; Heme oxygenase-1; Mesenchymal stromal cells; Acute lung injury; Endotoxemia
Contributor Information
Qun Lin
Department of Anesthesiology, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350004, China
Yiqing Guo
Department of Anesthesiology, Fujian Provincial Hospital and Provincial Clinical Medical College of Fujian Medical University, Fuzhou 350001, China
Xiaohua Lin
Department of Anesthesiology, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350004, China
Feng Chen
Fujian Provincial Institute of Emergency Medicine Emergency Department, Fujian Provincial Hospital, Fuzhou 350001, China
Jun Ke
Fujian Provincial Institute of Emergency Medicine Emergency Department, Fujian Provincial Hospital, Fuzhou 350001, China
Lihua Lei
Department of Anesthesiology, Fujian Provincial Hospital and Provincial Clinical Medical College of Fujian Medical University, Fuzhou 350001, China
