| Background: p38 MAPK is one of important signal transduction pathways in cell signaling related to inflammation, apoptosis and redox balance. NF-E2 related factor 2(Nrf2) is a key transcription factor in regulating antioxidant reactions and redoxbalance by regulating endogenous antioxidants. The current study is aim to determine whether electroacupuncture have protective effect by affecting p38MAPK- Keap1-Nrf2/ARE pathway against acute lung injury in rabbit models of endotoxin shock.Objective The current study aims to determine whether electroacupuncture promotes nuclear translocation of Nrf2 by affecting p38 MAPK pathway against acute lung injury in rabbit models of endotoxin shock.Methods Eighty healthy male New Zealand white rabbits, aged 2 months, weighting 1.5-2.0kg, were divided into eight groups randomly(n=10each): Normal control group(group C), p38 MAPK inhibitor SB203580 group(group S), LPS group(group M),LPS + SB203580 group(group MS), electroacupuncture + LPS group(group EAM), sham-electroacupunture +LPS group(group SEAM), electroacupuncture + LPS +SB203580(group EAMS) and shan-electroacupuncture + LPS + SB203580 group(group SEAMS). The rabbits were anesthetized with 20%urethane 5 ml/kg and tracheostomized and kept spontaneous breathing.Right common carotid artery was cannulated for mean arterial pressure monitoring.Ear vein was cannulated for drug administration. A dose of lipopolysaccharide(LPS) 5 mg/kg was injected intravenously to replicate the model of endotoxin induced acute lung injury. Endotoxin shock was confirmed by decreasing in mean arterial pressure to 75%of the baseline value within 2 h after LPS administration. SB203580 5μmol/kg was infused intravenously in group S, MS, EAMS and SEAMS. Bilateral 30 min electroacupuncture(wave length 0.2-0.6 ms,frequency 2-100 Hz,intensity≤2-3 m A) stimulation of Zusanli(ST36) and Feishu(BL13) was performed once a day for 4 days before establishment of endotoxin shock model and during the process of establishment of endotoxin shock model in EAM, EAMS groups. SEAM was performed at the points 0.5 cm lateral to the acupoint of Zusanli(ST36) and Feishu(BL13) according to the method previously described in group EAM. 6 hours after administration of LPS, blood samples were collected for biochemical measurements, and then sacrificed rabbits. Lung tissue were collected to calculatewet-to-dry weight ratios(W/D), histopathological examination, determination of p38 MAPK and p-p38 MAPK protein, Nrf2 total protein, Nrf2 nucleoproteinas well asthe distribution of Nrf2 protein in the nucleus.Results LPS caused severe extensive lung injury, which was lessened by treatment of electroacupuncture. Compared to group C, the pathological scores, MDA level and W/D ratio were significantly increased in M, MS, EAM, SEAM, EAMS and SEAMS group(P<0.05), and level of phosphorylation p38 MAPK and Nrf2 protein were increased in M, MS, EAM, SEAM, EAMS, SEAMS group(P<0.05). Compared to group M, the pathological scores, MDA level and W/D ratio were significantly decreased in EAM and EAMS group(P < 0.05), and level of phosphorylation p38 MAPK and Nrf2 protein were increased in EAM and EAMS group(P<0.05), and no significant changes in the index mentioned above were found in SEAM and SEAMS group(P>0.05). Compared to group EAM, the pathological scores, MDA level and W/D ratio were significantly decreased in group EAMS(P<0.05), and level of phosphorylation p38 MAPK and Nrf2 nucleus protein were decreased in group EAMS(P<0.05).Conclusion Electroacupuncture have protective effect in endotoxin shock induced ALI in rabbits, this effect may be related to the nuclear translocation of Nrf2 which may associate to the phosphorylation of p38 MAPK. |
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