目的 研究右美托咪啶对大鼠肺缺血再灌注损伤(IRI)中p38丝裂素活化蛋白激酶(p38MAPK)及肺组织高迁移率族盒蛋白1(HMGB1)表达的影响,为分析右美托咪啶的肺保护作用奠定基础.方法 将36只SD大鼠随机分为三组各12只:A组行假手术处理;B组建立大鼠急性肺IRI模型;C组在造模前以盐酸右美托咪啶预处理.手术3h后处死,取肺组织病理染色后观察组织病理学变化、行酶联免疫吸附试验检测肺组织髓过氧化酶(MPO)活性、行Western Blotting法检测肺组织磷酸化p38MAPK蛋白及HMGB1蛋白的表达.结果 与A组比较,B组肺组织出现明显病理学改变,MPO活性明显更强,磷酸化p38MAPK蛋白及HMGB1蛋白表达水平亦明显增加,上述差异均有统计学意义(P<0.05);与B组相比,C组上述各指标均明显下降,差异亦有统计学意义(P<0.05).磷酸化p38MAPK蛋白及HMGB1蛋白表达水平与肺组织病理损伤评分及MPO活性均呈显著正相关(P<0.05).结论 肺IRI时可能出现p38MAPK信号通路异常活跃、肺组织HMGB1过表达,右美托咪啶则能有效抑制p38MAPK信号通路及肺组织HMGB1表达,这可能是其发挥肺保护作用的机制之一.
Objective To study the influence of dexmedetomidine on p38MAPK signaling pathway of IRI in rat lung and HMGB1 expression in lung tissue. Methods 36 SD rats were randomly divided into three groups, 12 rats in each group. The group A was sham operation, the group B was to establish acute lung IRI model, and the group C was given dexmedetomidine pretreatment before making model. 3h after operation, the pathological changes after lung tissue pathological staining were observed, the activity of MPO of lung tissue was detected by enzyme linked immunosorbent assay (ELISA), and phosphorylated p38MAPK protein and HMGB1 protein of lung tissue were detec-ted by Western Blotting method. Results Compared with the group A, pathological changes of lung tissue and MPO activity were more obvious in the group B. Phosphorylated p38MAPK protein and the expression level of HMGB1 pro-tein significantly increased (P<0. 05). Compared with the group B, the indicators above in the group C decreased significantly (P<0. 05). Phosphorylated p38MAPK protein and the expression level of HMGB1 protein were posi-tively correlated with pathological damage score of lung tissue and the activity of MPO in lung tissues ( P<0. 05 ) . Conclusion P38MAPK signaling pathway may be abnormally active in lung IRI, over expression of HMGB1 in lung tissue, and dexmedetomidine can effectively inhibit P38MAPK signaling pathway and HMGB1 expression of lung tis-sues, which may be one of the mechanisms of the protective effect of the lung.