Effect Of ERK1/2and NF-κb Signaling Pathway In Electroacupuncture-mediated Up-regulation Of Heme Oxygenase-1in Lung Of Rabbits With Endotoxic Shock

The acute respiratory distress syndrome (ARDS), an indication of acute lung injury (ALI), is highly associated with septic shock. We have previously demonstrated that electroacupuncture stimulation at ST36and BL13, while not the non-acupoint, could attenuate the lung injury during the endotoxic shock, and this effect was due to increased expression of HO-1.Extracellular signal-regulated kinase1/2(ERK1/2) is a most common member of MAPK family. Recently, previous studies showed that EA significantly increased the phosphorylation levels of ERK.Nuclear facter-kappaB (NF-κB) is a key transcription factor in response to host defense against infection. Following the LPS challenge, NF-κB is translocates into the nucleus driving expression of a variety of inflammatory genes, which are involved in the pathogenesis of ALI.Therefore, our purpose was to study the role of ERK1/2and NF-κB in electroacupuncture-mediated up-regulation of heme oxygenase-1in injured lungs of rabbits with endotoxic shock.Objective To investigate the role of extracellular signal-regulated kinasesl/2(ERK1/2) pathways and Nuclear facter-kappaB (NF-κB) pathways on electroacupuncture-mediated up-regulation of heme oxygenase-1(HO-1) in the injured lungs of LPS-induced endotoxic shock.Methods Seventy rabbits were randomly divided into7groups: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 days1to5, and then received LPS to replicate the experimental model of injured lung induced by endotoxic shock. Finally, they were sacrificed by bloodletting at6h 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-a, determination of HO-lprotein and mRNA expression, and determination of ERK1/2protein.Sixty New Zealand white rabbits were randomly divided into six groups C, M, SEAM, EAM, PDTC and EAMP. Male New England white rabbits were given EA treatment on both sides once a day on days1to5, and then received LPS to replicate the experimental model of injured lung induced by endotoxic shock. The animals were sacrificed by bloodletting at6h after LPS administration. The blood samples were collected for serum examination, and the lungs were removed for pathology examination, for determination of wet to dry weight ratio, MDA content, SOD activity, determination of HO-1protein and mRNA expression, and determination of NF-κBp65protein.Results According to the results, after EA treatment, expression of HO-land ERK1/2was slightly increased than those in other groups, accompanied with less severe lung injury as indicated by lower index of lung injury score, wet to dry weight ratio, MDA content, serum tumor necrosis factor-a levels, and greater SOD activity(p<0.05for all). After pretreatment with ERK1/2inhibitor PD98059, the effect of EA treatment and expression of HO-1were suppressed (p<0.05for all).Compared with stimulation at a non-acupoint, EA at ST36and BL13was found to increase the expression of HO-1and NF-κBp65, at the same time, with less severe lung injury as indicated by the lower index of lung injury score, wet to dry weight ratio, MDA content and greater SOD activity(all p<0.05). After pretreatment with NF-κB inhibitor PDTC, the effect of electroacupuncture-mediated upregulation of heme oxygenase-1in the lung of rabbits with endotoxic shock was suppressed (all p<0.05).Conclusions After electroacupuncture stimulation at ST36and BL13, severe lung injury during the endotoxic shock was attenuated. The mechanism may be through upregulation of HO-1mediated by the signal transductions of ERK1/2pathways and NF-κB pathways. The mechanism may be through upregulation of HO-1mediated by the signal transductions of ERK1/2pathways and NF-κB pathways. Thus, the regulation of ERK1/2pathways and NF-κB pathways via electroacupuncture may be a therapeutic strategy for endotoxic shock.