依达拉奉对大鼠肺热缺血再灌注损伤保护作用的实验研究

Protective Effects of Edaravone on Lung Ischemia-reperfusion Injury in Rats

目的通过建立大鼠在体肺热缺血再灌注模型,探讨依达拉奉对大鼠肺缺血再灌注损伤的保护作用及可能机制。方法 40只大鼠随机分为5组,每组8只:①假手术组(A组),仅作开胸处理,静脉注射生理盐水3mL/kg;②缺血再灌注组(IR组),左肺接受45min的缺血,然后接受120min的再灌注,缺血前静脉注射生理盐水3mL/kg;③依达拉奉不同剂量治疗组(C1、C2、C3组),缺血前5min静脉注射稀释剂量的依达拉奉,左肺接受45min的缺血后再接受120min的灌注。实验结束时,留取各组动物的血液样本及左肺组织,测定血浆丙二醛(MDA)含量及肺组织匀浆超氧化物岐化酶(SOD)活性、诱导性一氧化氮合酶(iNOS)活性、肺组织的湿/干比(W/D)。结果 IR组与假手术组相比W/D、MDA含量i、NOS活性均明显升高,SOD活性明显降低;依达拉奉组与IR组相比,C2、C3组W/Di、NOS活性均显著降低(P<0.01),C1组差异无统计学意义(P>0.05);MDA含量显著降低,SOD活性明显升高,差异均有统计学意义(P<0.05或P<0.01)。结论依达拉奉可通过清除氧自由基、抑制脂质的过氧化、抑制iNOS的表达、减轻缺血再灌注细胞毒性作用而减轻炎症反应,对大鼠原位热缺血再灌注损伤有一定保护作用。

Objective To research the protection of edaravone on lung of rats during ischemia-reperfusion,and explore the possible mechanism. Methods Fourty rats were randomly divided into five groups：①sham operation group（Group A）,received sternotomy only; ②the ischemiaJreperfusion group （group I/R）,the left pulmonary hills of rats were ligated for 45minutes and then reperfused for 120 minutes; ③edaravone treated groups （GroupC1,Group C2 and Group C3 with different drug dosages）,the left pulmonary hills of rats were hgated for 45minutes and then were reperfused for 120 minutes and intravenous injection of edaravone 5 minutes before ischemia. At the end of the experiment, the left lung was harvested and blood sample was collected. Blood MDA,lung tissue wet-to-dry（W/D） ratio,inducible nitric oxide synthase（iNOS） and Superoxide Dismutase（SOD）were measured. Results The W/D ratio,blood MDA content,and iNOS activity were significantly higher in grouplR than those in group A,while the SOD activity was significant lower in group IR than those in group A. As compared with group IR,W/D ratio and iNOS activity were decreased remarkably in group C2 and C3 （P〈0.01）but those had no significant change in group C1 （P〉0.05）;Blood MDA content of group C was lower than it in group IR（P〈0.01）;SOD activity of group C was higher than it in group IR and the difference has statistical sense（P〈0.05）. Conclusion Edaravone has a protection on lung ischemia-reperfusion injury in rat lung warm ischemia model.h maybe through clearing oxygen free radical （OFR） and controlling effectively lipid peroxide,while it can alleviate ischemia -reperfusion cytotoxicity and reduce inflammatory reaction bv inhibiting iNOS exoression.