Role of p38 mitogen-activated protein kinase pathway in electro-acupuncture-induced reduction of endotoxic shock-induced acute lung injury in rabbits

Objective To evaluate the role of p38 mitogen-activated protein kinase (p38MAPK) pathway in electro-acupuncture (EA)-induced reduction of endotoxic shock-induced acute lung injury (ALI) in rabbits.Methods Seventy healthy male New Zealand white rabbits,aged 2 months,weighing 1.5-2.0kg,were randomly divided into 7 groups (n=10 each):normal control group (group C),anhydrous alcohol group (group A),specific p38MAPK blocker SB203580 group (group SB),endotoxic shock-induced ALI group (group ALI),EA + endotoxic shock-induced ALI group (group EA),sham EA + endotoxic shock-induced ALI group (group SEA),and EA + endotoxic shock-induced ALI + SB203580 group (group EAS).The animals were anesthetized with iv 20％ urethane 5ml/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.LPS 5 mg/kg (in 2 ml of normal saline) was injected intravenously in groups ALI,EA,SEA,EAS,while the equal volume of normal saline was injected in the other groups.Endotoxic shock was confirmed by decrease in mean arterial pressure to 75％ of the baseline value within 2h after LPS injection.SB203580 5 μmol/kg (in 0.5ml of anhydrous alcohol) was then infused intravenously at 0.05ml/min in groups SB and EAS,while the equal volume of normal saline was infused in group C and the equal volume of anhydrous alcohol was given in the other groups.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 and EAS groups.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 SEA.Arterial blood samples were taken at 6h after LPS or normal saline administration for detection of concentrations of serum tumor necrosis factor-α (TNF-α) and interleukin-10 (L-10).The rabbits were then sacrificed by exsanguination.The lungs were removed for microscopic examination and for measurement of phosphorylation of p38MAPK in lung tissues.The pathological changes of the lung were scored.Results Compared with group C,the pathological scores and serum TNF-α and L-10 concentrations were significantly increased in ALI,SEA,EA and EAS groups and phosphorylation of p38MAPK was increased in ALI,SEA and EA groups (P ＜ 0.05),and no significant changes were found in the parameters mentioned above in A and SB groups (P ＞ 0.05).Compared with group ALI,the pathological scores and serum TNF-α concentrations were significantly decreased and serum L-10 concentrations and phosphorylation of p38MAPK were increased in EA group,the pathological scores,serum TNF-α concentrations and phosphorylation of p38MAPK were decreased in EAS group (P ＜ 0.05),and no significant changes in the parameters mentioned above were found in SEA group (P ＞ 0.05).The pathological scores and serum TNF-α concentrations were significantly higher and phosphorylation of p38MAPK was lower in EAS group than in EA group (P ＜ 0.05).Conclusion p38MAPK pathway mediates EA-induced reduction of endotoxic shock-induced ALI in rabbits.文章序号>=10.3760/cma.j.issn.0254-1416.2013.08.022 Key words: Electro acupuncture;  p38Mitogen-activated protein kinases;  Lung;  Shock,septic