Role of TRPV1/NF-κB signaling pathway in dexmedetomidine-induced alleviation of VILI in rats / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the role of transient receptor potential vanilloid receptor 1 (TRPV1)/nuclear factor-κB (NF-κB) signaling pathway in dexmedetomidine-induced alleviation of ventilator-induced lung injury (VILI) in rats.Methods:One hundred clean-grade healthy male Sprague-Dawley rats, weighing 270-320 g, aged 4-5 months, were divided into 5 groups ( n=20 each) using a random number table method: control group (group C), VILI group (group V), AMG9810 group (group A), dexmedetomidine group (group D), and dexmedetomidine + RTX group (group DR). VILI model was prepared by mechanical ventilation with a tidal volume of 40 ml/kg for 4 h. In group A, TRPV1 inhibitor AMG9810 30 mg/kg was intraperitoneally injected at 1 h before mechanical ventilation.Dexmedetomidine 5.0 μg/kg was intravenously infused at 20 min before mechanical ventilation, and dexmedetomidine was intravenously infused at the rate of 5.0 μ g·kg -1·h -1 during ventilation in group D and group DR.In group DR, RTX 70 μ g/kg was intraperitoneally injected for 3 consecutive days before mechanical ventilation.At 4 h of mechanical ventilation, the concentrations of interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and IL-6 in bronchoalveolar lavage fluid (BALF) were detected, oxygenation index (OI) and wet/dry lung weight (W/D) ratio were measured, the histopathological changes of lung tissues were observed, and lung injury was assessed and scored.The expression of TRPV1 and NF-κB in lung tissues was detected by Western blot, and real-time polymerase chain reaction was used to detect the expression of TRPV1 and NF-κB mRNA. Results:Compared with group C, the concentrations of IL-1β, TNF-α and IL-6 in BALF were significantly increased, OI was decreased, the W/D ratio and lung injury scores were increased, and the expression of TRPV1 and NF-κB protein and mRNA was up-regulated in group V ( P<0.05). Compared with group V, the concentrations of IL-1β, TNF-α and IL-6 in BALF were significantly decreased, OI was increased, the W/D ratio and lung injury scores were decreased, and the expression of TRPV1 and NF-κB protein and mRNA was down-regulated in A, D and DR groups ( P<0.05). Compared with group D, the concentrations of IL-1β, TNF-α and IL-6 in BALF were significantly increased, OI was decreased, the W/D ratio and lung injury scores were increased, and the expression of TRPV1 and NF-κB protein and mRNA was up-regulated in group DR ( P<0.05). Conclusions:The mechanism by which dexmedetomidine alleviates VILI is partially related to inhibition of the activation of TRPV1/NF-κB signaling pathway and inhibition of the inflammatory responses in lung tissues of rats.