Effect of penehyclidine hydrochloride on expression of airway MUC5AC during ventilator-induced lung injury and the relationship with TLR4/MyD88 signaling pathway in rats
10.3760/cma.j.issn.0254-1416.2019.10.025
- VernacularTitle: 盐酸戊乙奎醚对大鼠呼吸机相关性肺损伤时气道MUC5AC表达的影响及其与TLR4/MyD88信号通路的关系
- Author:
Jun YAN
1
;
Chunrui YU
2
;
Lixin SUN
2
;
Fuguo MA
2
;
Fei SHI
2
;
Qiujie LI
2
;
Mingshan WANG
2
Author Information
1. Postgraduate Department of Shandong First Medical University & Shandong Academy of Medical Sciences, Taian 271000, China
2. Department of Anesthesiology, Qingdao Municipal Hospital, Qingdao 266071, China
- Publication Type:Journal Article
- Keywords:
Cholinergic antagonists;
Respiration, artificial;
Acute lung injury;
Mucin 5AC;
Toll-like receptor 4;
Myeloid differentiation factor 88
- From:
Chinese Journal of Anesthesiology
2019;39(10):1248-1252
- CountryChina
- Language:Chinese
-
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:Thirty-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 normal saline was given instead in S and VILI groups.At 4 h of mechanical ventilation, the arterial blood samples 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 expression 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:Compared 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-regulated 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:Penehyclidine 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.
