Role of α7nAChR in electroacupuncture-induced reduction of acute lung injury induced by endotoxin in rats: the relationship with JAK2/STAT3 signaling pathway / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the role of α7 nicotinic acetylcholine receptor (α7nAChR) in electroacupuncture (EA)-induced reduction of acute lung injury (ALI) induced by endotoxin and the relationship with Janus kinase 2/signal transducers and activators of transcription 3 (JAK2/STAT3) signaling pathway in rats.Methods Sixty clean-grade healthy male Sprague-Dawley rats,aged 8 weeks,weighing 200-220 g,were divided into 6 groups (n=10 each) using a random number table method:control group (group C),endotoxin-induced ALI group (group ALI),EA at acupoints plus ALI group (group EA),specific α7nAChR antagonist α-bungarotoxin (α-BGT) plus ALI group (group BA),EA at acupoints plus α-BGT plus ALI group (group EBA),and EA at non-acupoints plus ALI group (group SEA).ALI was induced by intravenously injecting lipopolysaccharide 5 mg/kg.EA stimulation of bilateral Zusanli and Neiguan acupoints was performed (frequency of disperse-dense wave 2/15 Hz,wave length 0.2-0.5 ms,intensity 1-2 mA) once a day (time for stimulation 900 to 1000,30 min per time) at 1-4 days before establishing the model in EA and EAB groups.EA was performed at the points 0.5 cm lateral to the acupoints of Zusanli and Neiguan with the same parameters of stimulation in group SEA.o-BGT 1 μg/kg was intraperitoneally injected at 30 min before establishing the model in BA and EBA groups.Rats were sacrificed at 6 h after injecting lipopolysaccharide,and lungs were removed for microscopic examination of the pathological changes which were scored and for determination of wet to dry weight ratio (W/D ratio),contents of tumor necrosis factor-alpha (TNF-α),interleukin-lbeta (IL-1β) and IL-6 (by enzyme-linked immunosorbent assay),and expression of α7nAChR,phosphorylated JAK2 (p-JAK2) and phosphorylated STAT3 (p-STAT3) (by Western blot).Results Compared with group C,the lung injury scores,W/D ratio and contents of TNF-α,IL-1β and IL-6 were significantly increased,and the expression of α7nAChR,p-JAK2 and p-STAT3 was up-regulated in the other five groups (P＜0.05).Compared with group ALI,the lung injury scores,W/D ratio and contents of TNF-α,IL-1β and IL-6 were significantly decreased,and the expression of α7nAChR,p-JAK2 and p-STAT3 was up-regulated in group EA,the lung injury scores,W/D ratio and contents of TNF-α,IL-1β and IL-6 were significantly increased,and the expression of o7nAChR,p-JAK2 and p-STAT3 was down-regulated in group BA (P＜0.05),and no significant change was found in the parameters mentioned above in group SEA (P＞0.05).Compared with group EA,the lung injury scores,W/D ratio and contents of TNF-α,IL-1β and IL-6 were significantly increased,and the expression of o7nAChR,p-JAK2 and p-STAT3 was down-regulated in group EBA (P＜0.05).Conclusion Up-regulated expression of α7nAChR activates JAK2/STAT3 signaling pathway,which is involved in EA-induced reduction of ALI in rats.