急性肺障害に対するSrcチロシンキナーゼインヒビターの効果

抄録

Background: Acute lung injury (ALI) can be easily developed by a variety of insults including intestinal ischemia-reperfusion injury (IIRI). Patients with ALI require mechanical ventilation (MV) which can worsen pre-exisiting lung injury. Src protein tyrosine kinase (PTK) family is signaling proteins involved in intracellular signal transduction related to acute inflammatory responses. The aim of the present study is to see if pharmacological inhibition of the Src PTKs might modulate ALI. Methods: Rats received intestinal ischemia by occluding the superior mesenteric artery for 30 min. Then, reperfusion was initiated by removal of the occlusion, and animals were ventilated for 4 hours with tidal volume of 15 ml/kg and PEEP of 0 cmH2O. Src inhibitors (PP2 or SU6656) were administered before MV. Blood gas was measured during MV. Lung injury was assessed by histological examination. Results: After MV, ALI was developed in non-treated animals with significantly lower PaO2 levels and more pathologically damaged lungs. Animals treated with Src inhibitors showed improved pulmonary function. Conclusion: Pharmacological inhibition of Src PTKs could be a potential therapy for ALI.