Effect of penehyclidine hydrochloride on expression of airway MUC5AC during ventilator-induced lung injury and the relationship with TLR4/MyD88 signaling pathway in rats / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the effect of penehyclidine hydrochloride on the expression of airway mucin 5AC(MUC5AC)during ventilator-induced lung injury(VILI)and the relationship with Toll-like receptor 4/myeloid differentiation factor 88(TLR4/MyD88)signaling pathway in rats.Methods Thir-ty-six clean-grade healthy male Sprague-Dawley rats,aged 6-8 weeks,weighing 200-250 g,were divided into 3 groups(n＝12 each)using a random number table method: sham operation group(group S),VILI group(group VILI),and penehyclidine hydrochloride group(group P).The rats were tracheotomized in group S.The rats were tracheotomized,connected to a small animal ventilator and mechanically ventilated for 4 h with the tidal volume of 20 ml/kg,respiratory rate 80 breaths/min,inspiratory/expiratory ratio 1 ∶1,and inspired oxygen fraction ratio 21％in VILI and P groups.At 30 min before mechanical ventilation,penehyclidine hydrochloride 2 mg/kg was injected via the tail vein in group P,and the equal volume of nor-mal saline was given instead in S and VILI groups.At 4 h of mechanical ventilation,the arterial blood sam-ples were taken for measurement of PaO2.The rats were then sacrificed,and broncho-alveolar lavage fluid(BALF)was collected for determination of interleukin-1β(IL-1β),IL-6 and tumor necrosis factor-α(TNF-α)concentrations by enzyme-linked immunosorbent assay.The lung specimens were collected for calculation of the wet/dry weight ratio(W/D ratio),for examination of pathological changes which were scored after haematoxylin and eosin staining(under a light microscope),and for determination of the ex-pression of MUC5AC(by immunohistochemistry),expression of TLR4,MyD88,p38 mitogen-activated protein kinase(p38MAPK)and nuclear factor-kappa B(NF-κB)in lung tissues(by Western blot),and expression of MUC5AC mRNA in lung tissues(by real-time polymerase chain reaction).Results Com-pared with group S,PaO2 was significantly decreased,the W/D ratio and lung injury score were increased,the expression of MUC5AC protein and mRNA was up-regulated,the concentrations of IL-1β,IL-6 and TNF-α in BALF were increased,and the expression of TLR4,p38MAPK,MyD88 and NF-κB was up-reg-ulated in VILI and P groups(P＜0.01).Compared with group VILI,PaO2 was significantly increased,the W/D ratio and lung injury score were decreased,the expression of MUC5AC protein and mRNA was down-regulated,the concentrations of IL-1β,IL-6 and TNF-α in BALF were decreased,and the expression of TLR4,p38MAPK,MyD88 and NF-κB was down-regulated in group P(P＜0.05).Conclusion Penehy-clidine hydrochloride can decrease the expression of airway MUC5AC during VILI,and the mechanism may be related to inhibiting activation of TLR4/MyD88 signaling pathway in rats.