Role of p38MAPK signaling pathway in electroacupuncture-induced reduction of ALI in rabbits with endotoxic shock: the relationship with Nrf2

Abstract

Objective To evaluate the role of p38MAPK signaling pathway in electroacupuncture (EA)-induced reduction of acute lung injury (ALI) in rabbits with endotoxic shock and the relationship with nuclear factor E2-related factor 2 (Nrf2). Methods Seventy healthy male New Zealand white rabbits, aged 2 months, weighing 1.5-2.5 kg, were randomly divided into 7 groups (n=10 each) using a random number table: control group (group C), endotoxin-induced ALI group (group A), p38MAPK inhibitor SB203580 group (group SB), ALI + SB203580 group (group A-SB), ALI + EA group (A-EA group), ALI + EA at non-acupoint group (A-NEA group) and ALI + EA at acupoints+ SB203580 group (A-EA-SB group). The rabbits were anesthetized with urethane and tracheostomized and kept spontaneous breathing.Right common carotid artery was cannulated for mean arterial pressure monitoring.The auricular vein was cannulated for drug administration.Bilateral 30 min EA (wave length 0.2-0.6 ms, frequency 2/100 Hz, intensity≤1-2 mA) stimulation of Zusanli and Feishu was performed once a day for 4 days before establishment of the model and during establishment of the model in A-EA and A-EA-SB groups.In group A-NEA, EA was performed at the points 0.5 cm lateral to the acupoints of Zusanli and Feishu according to the method previously described in group EA.In A, A-SB, A-EA, A-NEA and A-EA-SB groups, ALI was induced by endotoxin (5 mg/kg) injection, while the equal volume of normal saline was given in C and SB groups.After establishment of the model, SB203580 5 μmol/kg was injected intravenously in SB, A-SB and A-EA-SB groups, the equal volume of normal saline was given in group C, and the equal volume of dehydrated alcohol was given in the other groups.At 6 h after endotoxin or normal saline administration, arterial blood samples were collected for blood gas analysis.The rabbits were then sacrificed, and lungs were removed for microscopic examination and for determination of malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, and expression of phosphor-p38MAPK (p-p38MAPK) and Nrf2 in lung tissues.The pathological changes of lungs were scored.Wet to dry lung weight ratio (W/D ratio) was calculated. Results Compared to group C, the pathological scores, W/D ratio, MDA content, and expression of p-p38MAPK and Nrf2 were significantly increased, and SOD activities were decreased in A, A-SB, A-EA, A-NEA and A-EA-SB groups.Compared to group A, the pathological scores, W/D ratio and MDA content were significantly decreased, and SOD activities and expression of p-p38MAPK and Nrf2 were increased in A-EA group.Compared to group A-EA, the pathological scores, W/D ratio and MDA content were significantly increased, and SOD activities and expression of p-p38MAPK and Nrf2 were significantly decreased in group A-EA-SB. Conclusion p38MAPK signaling pathway mediates EA-induced reduction of ALI in rabbits with endotoxic shock, and up-regulated expression of Nrf2 is involved in the mechanism. Key words: p38 mitogen-activated protein kinases; Electric stimulation therapy; Shock, septic; Respiratory distress syndrome, adult; NF-E2-related factor 2