Role of nuclear factor-kappaB in electro-acupuncture-induced up-regulation of heme oxygenase-1 expression in rabbits with endotoxic shock-induced acute lung injury

Abstract

Objective To investigate the role of nuclear factor-kappaB (NF-κB) in electro-acupuncture (EA)-induced up-regulation of heme oxygenase-1 (HO-1) expression in rabbits with endotoxic shock-induced acute lung injury (ALI).Methods Sixty New Zealand white rabbits,aged 2 months,weighing 1.5-2.0kg,were randomly divided into 6 groups (n=10 each):control group (group C),endotoxic shock-induced ALI group,sham EA + ALI group (SEA group),EA + ALI group (EA group),PDTC (NF-κB inhibitor) group,and EA + ALI + PDTC group (EAP group).The animals were anesthetized with intramuscular xylazine hydrochloride 0.8 mg/kg and tracheostomized.Ear vein was cannulated for drug administration.Lipopolysaccharide (LPS) 5 mg/kg was injected intravenously in ALI,SEA,EA and EAP groups,while the equal volume of normal saline (NS) was given instead in C and PDTC groups.Endotoxin shock was confirmed by decrease in blood pressure by 25％ of the baseline value.PDTC 20 mg/kg was infused intravenously at 0.5 h before LPS or NS injection in PDTC and EAP groups,while the equal volume of NS was given instead in the other groups.15 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 endotoxic shock model and on the day of establishment of endotoxic shock model in EA and EAP groups.The model was established at 30 min after the end of the last EA.The animals were sacrificed by blood-letting at 6h after LPS or NS administration.The lungs were removed for microscopic examination and for caculation of wat/dry weight ratio(W/D ratio),and for determination of malondialdehyde (MDA) content,superoxide dismutase (SOD) activity,the expression of HO-1 protein and mRNA and NF-κBp65 protein.The pathological changes of the lung was scored.Results Compared with group C,the pathological scores,W/D ratio and MDA content were significantly increased,SOD activity was decreased,and the expression of HO-1 protein and mRNA,and intranuclear NF-κBp65 protein was up-regulated in ALI,SEA,EA and EAP groups (P ＜ 0.05),and no significant changes in the parameters mentioned above were found in PDTC group (P ＞ 0.05).Compared with group ALI,the pathological scores,W/D ratio and MDA content were significantly decreased,SOD activity was increased,and the expression of HO-1 protein and mRNA,total NF-κBp65 protein and intranuclear NF-κBp65 protein was up-regulated in EA group,and the pathological scores,W/D ratio and MDA content were significantly increased,SOD activity was decreased,and the expression of HO-1 protein and mRNA,and intranuclear NFκBp65 protein was down-regulated in group EAP (P ＜ 0.05),and no significant changes in the parameters mentioned above were found in SEA group (P ＞ 0.05).Compared with group EA,the pathological scores,W/D ratio and MDA content were significantly increased,SOD activity was decreased and the expression of HO-1 protein and mRNA,total NF-κBp65 protein,and intranuclear NF-κBp65 protein was down-regulated in EAP group (P ＜0.05).Conclusion Activated NF-κB mediates EA-induced up-regulation of HO-1 expression and is involved in EA-induced reduction of endotoxic shock-induced ALI in rabbits. Key words: Electroacupuncture ;  NF-kappa B ;  Heme oxygenase-1 ;  Shock, septic ;  Respiratory distress syndrome, adult