p38 MAPK在机械通气所致肺损伤中的作用

The role of p38 mitogen-activated protein kinase in the injury induced by mechanical ventilation

目的 研究P38丝裂原激活蛋白激酶（P38 MAPK）在机械通气所致肺损伤中的作用。方法 15只普通健康80日龄家猪,随机分为3组:A组（VT=16ml/kg,PEEP=0）,B组（VT=6Ml/kg,PEEP=16cm H2O）和 C组（VT=6 ml/kg,PEEP=8cm H2O）。机械通气3h后在光镜下观察肺组织的病理学改变,并采用免疫组化检测肺组织ICAM-1的表达水平、Western Blot法测定肺组织p38MAPK及磷酸化p38MAPK的含量。结果 光镜下A、B两组有明显肺组织损伤,C组则无明显肺损伤表现。A、B两组肺泡上皮、肺间质及肺血管内皮细胞ICAM-1表达均呈阳性,C组肺组织ICAM-1表达阴性。三组间肺组织中未磷酸化P38MAPK含量无显著性差异（P>0.05）,而A、B两组肺组织的磷酸化p38 MAPK含量显著高于C组（P<0.05）。结论 大VT或小VT高PEEP可导致急性肺损伤,P38 MAPK介导了炎症反应所致的急性肺损伤。

Objective The purpose of this study was to investigate the role of p38 mitogen-activated protein kinase ( p38 MAPK) in the lung injury induced by mechanical ventilation.Methods Fifteen healthy 80 day-old pigs weighing (22.5 ± 1.5)kg were randomly divided into three groups according to the tidal volume(VT) and PEEP of mechanical ventilation: group A (VT = 16ml·kg-1, PEEP = 0) ; group B (VT = 6 ml·kg-1, PEEP= 16cm H2O) and group C(VT = 16ml·kg-1, PEEP = 8cm H2O). The animals were mechanically ventilated for 3h, then sacrificed by exsanguination. Right lower lobe was immediately removed for identification of intercellular adhesion molecule-1 ( ICAM-1 ) expression using immunohistological technique, determination of phosphorylated p38 MAPK content using Western Blot and microscopic examination. Results There was significant histological changes in the lung tissue in group A and B, but no significant histological changes were found in group C. The expression of ICAM-1 was positive in the lung in group A and B but negative in group C. The level of phosphorylated p38 MAPK among the 3 groups. Conclusion Acute lung injury can be induced by mechanical ventilation with high tidal volume or low tidal volume plus high PEEP, p38 MAPK may mediate the inflammatory response-induced lung injury.