Role of Rho/Rock signaling pathways in ventilator-induced lung injury in rats / 临床麻醉学杂志

ABSTRACT

Objective To investigate the role of Rho/Rock signaling pathways in ventilator-in-duced lung injury in rats.Methods Ninety-six male SD rats,weighing 300-350 g,were equally and randomly divided into four groups using a random number table (n =24 each)control group (group C),fasudil group (group F),high tidal volume group (group H)and high tidal volume + fasudil group (group HF).Rats in group C and group F received no mechanical ventilation,rats in group H and group HF were intubated and mechanically ventilated (VT = 40 ml/kg,RR = 40 beats per minutes,FiO 2 =40%)for 4 h.The animals in group F and group HF were given intraperitoneal in-jection of fasudil 10 mg/kg at the time 1 h before mechanically ventilated.Six rats were chosen in each group at the time before ventilation (T0 )and at 4,8,24 h after ventilation (T1-T3 ),and blood sam-ples were taken for determination of the levels of serum tumor necrosis factor-α (TNF-α),IL-6 and IL-10,lungs were removed,bronchoalveolar lavage fluid (BALF)was collected to examine protein content,wet/drying (W/D)ratio was determined,which were then stained with haematoxylin and e-osin and examined under microscope,the pathological changes of lungs were scored.Myeloperoxidase (MPO)activity in lung tissue was determined by spectrophptometry.Protein and gene expression of RhoA and Rock2 in the lung tissue were detected by Western blot and reverse transcription PCR (RT-PCR).Results Compared with group C,the serum TNF-α,IL-6 and IL-10,BALF protein content, W/D ratio,the pathological scores,MPO activity,the expression of RhoA,Rock2 protein and mR-NA were significantly increased in group H and HF at T1-T3 (P <0.05 ).Compared with group H, the serum TNF-αand IL-6,BALF protein content,W/D ratio,the pathological scores,MPO activi-ty,the expression of RhoA,Rock2 protein and mRNA were significantly decreased,and the serum IL-10 was significantly increased in group HF at T1-T3 (P <0.05).Conclusion Fasudil can attenuate ventilator-induced lung injury in rats,and the mechanism may be associated with inhibition of the Rho/Rock signaling pathways reducing the inflammatory response.