Mechanism of electroacupuncture-induced reduction of acute lung injury induced by endotoxic shock in rabbits: the relationship with Nrf2/ARE pathway

Abstract

Objective To investigate the relationship between the mechanism of electroacupuncture (EA)-induced reduction of acute lung injury induced by endotoxic shock (ES) and nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway in rabbits.Methods Forty healthy male New Zealand white rabbits,aged 2 months,weighing 1.5-2.0 kg,were randomly divided into 4 groups (n =10 each) using a random number table:sham operation group (group S),group ES,EA at acupoints + ES group (group EA),and EA at non-acupoints + ES group (group NA-EA).The animals were anesthetized with iv 20％ urethane 5 ml/kg,tracheostomized and kept spontaneous breathing.ES was induced by iv administration of lipopolysaccharide (LPS) 5 mg/kg in ES,EA and NA-EA groups.The equal volume of normal saline was given in group S.Bilateral 30 min EA (wave length 0.2-0.6 ms,frequency 2/100 Hz,intensity ≤2-3 mA) stimulation of Zusanli and Feishu was performed once a day for 4 days before establishment of endotoxic shock model and during the process of establishment of endotoxic shock model in EA group.In NA-EA group,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.The rabbits were sacrificed at 6 h after LPS or normal saline administration,and lungs were removed for microscopic examination and for determination of wet to dry lung weight ratio (W/D ratio),malondialdehyde (MDA) contents,superoxide dismutase (SOD) activities,and expression of Nrf2 mRNA in lung tissues and Nrf2 in nucleoprotein and total protein.The pathological changes of lung were scored.The ratio of Nrf2 expression in nucleoprotein to Nrf2 expression in total protein (N/T ratio) was calculated.Results Compared with group S,W/D ratio,MDA contents,and lung injury scores were significantly increased,the activities of SOD were decreased,the expression of Nrf2 mRNA in lung tissues and Nrf2 in nucleoprotein and total protein was up-regulated,and N/T ratio was increased in ES,EA and NA-EA groups.Compared with group ES,W/D ratio,MDA contents,and lung injury scores were significantly decreased,the activities of SOD were increased,the expression of Nrf2 mRNA in lung tissues and Nrf2 in nucleoprotein and total protein was up-regulated,and N/T ratio was increased in EA group,and no significant changes were found in NA-EA group.Conclusion The mechanism by which EA reduces acute lung injury induced by ES may be related to activation of Nrf2/ARE pathway and enhancement of antioxidant capacity in rabbits. Key words: Electroacupuncture; NF-E2-related factor 2; Response elements; Shock, septic; Respiratory distress syndrome, adult