非对称二甲基精氨酸在大鼠脑缺血再灌注损伤诱导的急性肺损伤发病过程中的作用(英文)

目的研究非对称二甲基精氨酸(ADMA)在大鼠脑缺血再灌注(I/R)诱导的急性肺损伤发病过程中的作用。方法成年雄性SD大鼠随机分为假手术组(S)、模型组(I/R)、ADMA处理组(ADMA+I/R)和DDAH处理组(DDAH+I/R)。通过大鼠脑缺血2 h后恢复血流灌注诱导急性肺损伤。在恢复血流灌注24 h后,采用比色法检测各组大鼠肺组织一氧化氮合酶(NOS)活性和NO含量。采用RT-PCR和Western blotting分别检测肺组织蛋白激酶(PKC)和肌球蛋白轻链激酶(MLCK)mRNA和蛋白表达水平;ELISA法检测支气管肺泡灌洗液及入肺血和出肺血血浆中的ADMA水平。结果脑I/R损伤大鼠支气管肺泡灌洗液和入肺血血浆中ADMA水平明显升高,肺组织中NO含量和NOS活性明显降低(P<0.05),同时MLCK和PKC mRNA和蛋白表达明显上调(P<0.05)。预先给予外源性DDAH后,脑缺血/再灌注损伤大鼠支气管肺泡灌洗液和入肺血血浆中ADMA水平明显降低,肺组织NO含量和NOS活性明显升高,MLCK和PKC mRNA和蛋白表达明显下调(P<0.05)。结论 ADMA通过上调肺组织MLCK和PKC的表达参与了脑I/R损伤后急性肺损伤的发病过程。ADMA可能是脑缺血/再灌注损伤诱导急性肺损伤的一个新的生物标志物和治疗靶点。

Role of asymmetric dimethylarginine in acute lung injury induced by cerebral ischemia/reperfusion injury in rats

Objective To determine the role of asymmetric dimethylarginine (ADMA) in acute lung injury induced by cerebral ischemia/reperfusion (I/R) injury in rats.Methods Adult male SD rats were randomly divided into 4 groups,namely the sham-operated group (S),cerebral I/R model group,ADMA + I/R group,and dimethylarginine dimethylaminohydrolase (DDAH)+I/R group.In the latter 3 groups,acute lung injury was induced by left middle cerebral artery occlusion for 120 min.After a 24-h reperfusion,the rats were sacrificed and the activities of nitric oxide synthase (NOS) and contents of nitric oxide (NO) were measured using reductase and colorimetric assay.The mRNA and protein expressions of protein kinase C (PKC)and myosin light chain kinase (MLCK) in the lung tissues were detected with RT-PCR and Western blotting,respectively.The contents of ADMA in the bronchoalveolar lavage fluid (BALF) and blood flowing into and out of the lungs were measured by ELISA.Results Cerebral I/R injury caused significantly elevated ADMA levels in the BALF and blood flowing into the lungs,and obviously lowered the NO concentration and NOS activity in the lung tissues (P＜0.05).Following cerebral I/R injury,MLCK and PKC mRNA and protein expressions were significantly upregualted in the lung tissues (P＜O.05).Exogenous DDAH obviously decreased the levels of ADMA in the BALF and blood flowing into the lungs,increased NO concentration and NOS activity,and down-reguahed MLCK and PKC mRNA and protein expressions in lung tissues of rats with cerebral I/R injury (P＜0.05).Conclusion ADMA contributes to the development of acute lung injury following cerebral I/R injury in rats by upregulating MLCK and PKC expression.ADMA may serve as a novel therapeutic biomarker and a potential therapeutic target for acute lung injury induced by cerebral I/R injury.