Effect of lidocaine on Rho/ROCK signaling pathway during endotoxin-induced acute lung injury in rats

Abstract

Objective To evaluate the effect of lidocaine on Ras homologue(Rho)/Rho kinase(ROCK)signaling pathway during endotoxin-induced lung injury(LI) in rats. Methods Forty SPF male Wistar rats, aged 5-8 weeks, weighing 200-250 g, were divided into 5 groups(n=8 each)using a random number table method: control group(group C), lipopolysaccharide(LPS)group(group LPS)and lidocaine at 3 different doses groups(L1-3 groups). LI was induced by intraperitoneal LPS 5 mg/kg(0.1 ml). The equal volume of normal saline was given intraperitoneally in group C. Lidocaine 2, 4 and 8 mg/kg was intraperitoneally injected at 1 h before LPS administration in L1-3 groups, respectively.The animals were sacrificed at 6 h after LPS or normal saline administration.Broncho-alveolar lavage fluid(BALF)was collected for determination of concentrations of interleukin-1 beta(IL-1β), IL-6 and tumor necrosis factor-alpha(TNF-α)(by enzyme-linked immunosorbent assay). The lung tissues were obtained for examination of the pathological changes which were scored and for measurement of the wet/dry weight ratio(W/D ratio)and activities of myeloperoxidase(MPO)and for determination of the expression of Rho, ROCK1, ROCK2, myosin phosphatase target protein 1(MYPT1), phosphorylated MYPT1(p-MYPT1)and ZO-1(by Western blot). The phosphorylation of MYPT1 was calculated. Results Compared with group C, the activity of MPO, lung injury score, W/D ratio and concentrations of IL-1β, IL-6 and TNF-α in BALF were significantly increased, the expression of Rho, ROCK1 and ROCK2 was up-regulated, the phosphorylation of MYPT-1 was increased, and the expression of ZO-1 was down-regulated in the other four groups(P<0.05). Compared with group LPS, the activity of MPO, lung injury score, W/D ratio and concentrations of IL-1β, IL-6 and TNF-α in BALF were significantly decreased, the expression of Rho, ROCK1 and ROCK2 was down-regulated, the phosphorylation of MYPT-1 was decreased, and the expression of ZO-1 was up-regulated in L1-L3 groups(P<0.05). Conclusion Lidocaine can inhibit activation of Rho/ROCK signaling pathway during endotoxin-induced LI in rats, and the effect may be related to the anti-inflammatory mechanism of lidocaine. Key words: Lidocaine; Rho factor; rho-Associated kinases; Endotoxemia; Respiratory distress syndrome, adult