Effect of ERK1/2 Signaling Pathway in Electro-Acupuncture Mediated Up-Regulation of Heme Oxygenase-1 in Lungs of Rabbits with Endotoxic Shock
Yuan Zhang, Jian-bo Yu, Xiao-qing Luo, Li-rong Gong, Man Wang, Xin-shun Cao, Shu-an Dong, Yu-miao Yan, Yihyun Kwon, Jia He
Department of Anesthesiology, Tianjin Nan Kai Hospital, Tianjin Medical University, Tianjin, China (mainland)
Med Sci Monit 2014; 20:1452-1460
The anti-oxidative and anti-inflammatory activities of electro-acupuncture (EA), a traditional clinical method, are widely accepted, but its mechanisms are not yet well defined. In this study, we investigated the role of extracellular signal-regulated kinases1/2 (ERK1/2) pathways on electro-acupuncture – mediated up-regulation of heme oxygenase-1 (HO-1) in rabbit lungs injured by LPS-induced endotoxic shock.
Material and Methods: Seventy rabbits were randomly divided into 7 groups: group C, group M, group D, group SEAM, group EAM, group EAMPD, and group PD98059. Male New England white rabbits were given EA treatment on both sides once a day on days 1–5, and then received LPS to replicate the experimental model of injured lung induced by endotoxic shock. Then, they were killed by exsanguination at 6 h after LPS administration. The blood samples were collected for serum examination, and the lungs were removed for pathology examination, determination of wet-to-dry weight ratio, MDA content, SOD activity, serum tumor necrosis factor-α, determination of HO-1 protein and mRNA expression, and determination of ERK1/2 protein.
Results: The results revealed that after EA treatment, expression of HO-1and ERK1/2 was slightly increased compared to those in other groups, accompanied with less severe lung injury as indicated by lower index of lung injury score, lower wet-to-dry weight ratio, MDA content, and serum tumor necrosis factor-α levels, and greater SOD activity (p<0.05 for all). After pretreatment with ERK1/2 inhibitor PD98059, the effect of EA treatment and expression of HO-1 were suppressed (p<0.05 for all).
Conclusions: After electro-acupuncture stimulation at ST36 and BL13, severe lung injury during endotoxic shock was attenuated. The mechanism may be through up-regulation of HO-1, mediated by the signal transductions of ERK1/2 pathways. Thus, the regulation of ERK1/2 pathways via electro-acupuncture may be a therapeutic strategy for endotoxic shock.
Keywords: Animals, Analysis of Variance, Blotting, Western, DNA Primers, Electroacupuncture - methods, Gene Expression Regulation, Enzymologic - physiology, Heme Oxygenase-1 - metabolism, Histological Techniques, Lipopolysaccharides - adverse effects, Lung - pathology, MAP Kinase Signaling System - physiology, Polymerase Chain Reaction, Rabbits, Shock, Septic - therapy, Superoxide Dismutase - blood, Tumor Necrosis Factor-alpha - blood