腺苷对肺缺血再灌注大鼠NOS活性的影响

Effect of Adenosine on Nitric Oxide Synthase Activity of Rats Subjected to Lung Ischemia-Reperfusion

目的:观察腺苷(Adenosine)对大鼠肺缺血再灌注损伤(I/R)的保护作用及一氧化碳合酶(NOS)活性的影响。方法:将60只清洁级SD大鼠随机分为假手术组(Sham组,开胸但不阻断肺门)、I/R组(开胸后左肺门阻断60min+开放再灌注120min)、Adenosine预处理组,每组20只。A-denosine预处理组术前30min开始由股静脉持续静脉滴入Adenosine(0.1mg/kg/min)。实验结束前测定各组平均肺动脉压(mPAP)、动脉血氧分压(PaO2)、肺湿/干重比(W/D)及血清和肺组织匀浆中内皮型一氧化碳合酶(eNOS)、诱导型一氧化碳合酶(iNOS)活性。结果:I/R组mPAP、W/D均高于Sham组(P<0.01),PaO2低于Sham组(P<0.01)。与I/R组比较,Adenosine预处理组mPAP、W/D明显降低,PaO2显著增高。与Sham组比较,I/R组血清及肺组织匀浆中eNOS活性明显降低,iNOS活性显著增加(P<0.01);Adenosine预处理能明显升高I/R大鼠eNOS活性,降低iNOS活性(与I/R组比较,P<0.01)。结论:Adenosine可通过减轻再灌注后肺水肿、降低肺动脉压及改善肺组织氧合功能,从而有效实现对I/R肺组织的保护,其保护作用可能与NOS不同亚型的表达变化有关。

Objective:To observe the protection of adenosine on lung ischemia-reperfusion injury and its effect on nitric oxide synthase(NOS) activity in rats.Method:60 rats were randomly divided into 3 groups.Sham group:received sternotomy only and no ischemia; I/R group:the left lungs of rats were rendered ischemia by ligating the left pulmonary hili for 60 minutes followed by 120 minutes reperfusion; Adenosine group:adenosine (0.1mg/kg/min) was administered intravenously 30 minutes prior to ischemia through femoral vein.Results:W/D and mPAP in I/R group were higher than those in sham group(P<0.01),while PaO2 was lower (P<0.01).Compared with I/R group,W/D and mPAP in adenosine group were significantly decreased,while PaO2 was remarkably increased (P<0.01).Compared with sham group,constitutive nitric oxide synthase(eNOS) activity of I/R group in serum and lung tissue were decreased,while inductible nitric oxide synthase(iNOS) activity increased (P<0.01).The pretreatment of adenosine significantly increased eNOS activity of I/R rat,and remarkably decreased iNOS activity (compared with I/R group,P<0.01).Conclusion:Adenosine can protect lung tissue from ischemia-reperfusion injury by reducing reperfusion pulmonary edema,decreasing pulmonary arterial pressure and improving oxygenation function.It may be related to alteration of NOS expression.