关键词: 右美托咪定, 呼吸机相关性肺损伤, Ras同源基因家族成员A/Rho激酶1(RhoA/ROCK1)信号通路

Abstract: Objective To investigate the effect of dexmedetom idine (DEX) on lung tissue and Ras homolog gene family member A (RhoA)/Rho kinase 1 (ROCK1) signaling pathway in lung tissue of rats with ventilator-induced lung injury (VILI). Methods A VILI rat model was established and separated into control group, model group (VILI group), dexmedetomidine low and high dose groups (DEX-L,DEX-H group), and high dose dexmedetomidine+lysophosphatidic acid (LPA) group (DEX-H+LPA group). Determination of wet/dry mass ratio of rat lung tissue (W/D); HE staining microscopy was applied to observe morphology of lung tissue; ELISA kit was applied to detect the level of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in bronchoalveolar lavage fluid (BALF); TUNEL staining method was applied to detect lung epithelial cell death; Immunoblotting was applied to detect the expression levels of apoptosis-related proteins, and RhoA, ROCK1 proteins. Results DEX could reduce lung injury, lung injury score, W/D, apoptosis rate, levels of TNF-α, IL-1β, IL-6, and expression of Bax, cleaved caspase-3, RhoA, ROCK, α-SMA in VILI rats (P＜0.05), while increased the expression of Bcl-2(P＜0.05); LPA could aggravate lung injury and increase lung injury score, W/D, apoptosis rate, level of TNF-α, IL-1β, IL-6 and expressions of Bax, cleaved caspase-3, RhoA, ROCK and α-SMA(P＜0.05); Bcl-2 expression level was decreased (P＜0.05). Conclusions Dexmedetomidine may protect rats with ventilator-induced lung injury by the inhibition of RhoA/ROCK1 signaling pathway.

Key words: dexmedetomidine, ventilator-induced lung injury, Ras homolog gene family member A/Rho kinase 1 (RhoA/ROCK1) signaling pathway