卡立泊来德对离体肺缺血再灌注损伤的初步实验研究 医学论文

1、    卡立泊来德对离体肺缺血再灌注损伤的初步实验研究 医学论文              本文由中国论文范文收集整理。              作者：周荣华，陈果，蒲江涛，陈艳芳，刘馨烛，张艳菊，龙村，刘斌  【摘要】  目的 研究 选择性钠/氢离子(Na+/H+ )交换阻断剂卡立泊来

2、德(Cariporide)对离体大鼠肺缺血/再灌注损伤的防治效果。 方法 建立离体大鼠肺缺血再灌注损伤模型。18只SD成年大鼠随机分为3组，每组6只：对照组:采用含5羟乙基淀粉的KHHB(Krebs - Henseleit hydroxyethylamylopectine buffer)灌注液持续平衡灌注、通气120 min；缺血再灌注组:平衡30 min后，缺血60 min、再灌注30 min； Cariporide组:平衡15 min，给予Cariporide预处理15 min，缺血60 min、再灌注30 min。持续监测并记录肺动脉压(PAP)；留取再灌注末灌注液,测定超氧化物歧化酶(

3、SOD) 活性和丙二醛(MDA) 含量；再灌注结束，测肺湿/干重比(W/D)；光、电镜观察肺病 理学 改变。 结果 缺血再灌注组PAP、MDA含量、SOD活性和W/D 较对照组明显升高(P<0.05)，SOD 活性显著下降(P<0.05)。Cariporide能明显减少PAP、MDA和W/D的增加，提高SOD活性(P<0.05)，显微、超微结构证实Cariporide组肺血管内皮及肺泡上皮的病理变化明显减轻。结论 Cariporide 能降低离体大鼠肺缺血再灌注损伤。 【关键词】  Na+/H+ 交换； 卡立伯来德；肺；缺血再灌注损伤Abstract: OBJECT

4、IVE   To investigate the protective effects of selective Na+/H+ exchanger cariporide on isolated rat lung ischemia and reperfusion injury.  METHODS  The isolated lung ischemia/reperfusion models were established. After equilibration, eighteen adult S.D rats were randomly divided

5、into three groups: the control group(n=6),the  ischemia/reperfusion group (n=6) and the cariporide group (n=6). In the control group, the isolated rat lungs were continuously perfused with the Krebs - Henseleit hydroxyethylamylopectine buffer (KHHB) solution for 120min. In the ischemia/reperfus

6、ion group, the isolated rat lungs were reperfused for 30min after 60min of ischemiaIn the cariporide group, cariporide was administered in the KHHB solution before ischemia. Pulmonary artery pressure (PAP) were continuously monitored. The KHHB solution at 30min of repefusions was collected to measur

7、e the malondialdehyde(MDA) content and superoxide dismutase (SOD) activity. After reperfusion, wet to dry lung weight ratio(W/D) was measured. The morphologic changes were also observed under light and electronic microscopes.  RESULTS  PAP,MDA and W/D in the ischemia/reperfusion group were

8、 significantly higher than those in the control group (P<0.05), and the SOD activity was lower than that in the control group (P<0.05). While, compared with the ischemia/reperfusion group, cariporide significantly reduced the PAP, MDA and W/D(P<0.05), and significantly increased the SOD act

9、ivity(P<0.05). The morphologic and ultrastructural damages in the cariporide group were milder than those in ischemia/reperfusion group.  CONCLUSION  Cariporide can significantly protect lung injury induced by ischemia and reperfusion in the isolated rat.Key words：  Na+/H+ exchange

10、r; Cariporide; Lung; Ischemia/reperfusion injury肺缺血再灌注损伤广泛存在于临床，例如：各种体外循环手术、肺移植术、心肺联合移植术后、肺血栓内膜剥除术及肺栓塞溶栓 治疗 ，以肺水肿、肺动脉高压为主要表现1，直接 影响 患者预后，但无特效防治方法。已有研究表明，选择性钠氢离子交换（Na+/H+ exchanger isoform-1, NHE1）阻断剂卡立泊来德（Cariporide）能减轻心肌缺血再灌注损伤2-3。而肺组织中也同样存在NHE14-5，Cariporide是否对肺缺血再灌注损伤存在作用，尚不清楚。本研究通过建立离体大鼠肺缺血再灌注模型

11、，探讨Cariporide对肺缺血再灌注损伤的防治效果。1  材料和方法1.1  离体肺缺血再灌注模型  SD成年大鼠（雌雄不限，体重275345 g），用3%戊巴比妥钠(40 mg/kg)腹腔注射麻醉，腹腔注入肝素(1000 U/kg)行全身肝素化，待后爪反射消失，气管切开插管，接微型人工呼吸机（江湾型）行控制呼吸(呼吸频率60次/min，潮气量6 ml/min)。正中劈开胸骨开胸，游离肺动脉，套线备用。经右心室插管至肺动脉主干（20G Y型套管针），结扎固定。迅速完整取下整个心肺组织，置于Langendorff灌流装置（Bridge AD Instrument PTY Ltd, Australia）， 37、95%O2、5%CO2饱和的含5羟乙基淀粉的改良KHHB(Krebs - Henseleit hydroxyethylamylopectine buffer)灌注液6、以30cm的高度落差经肺动脉插管非循环灌注肺脏，流量10 ml/min，并迅速剪开左心耳，以利于肺灌注液的引流。停止人工灌注和机械通气定义为：37常温肺缺血,保湿，缺血期肺内注入1.5 ml空气后夹闭气管；同时恢复灌注和机械通气则为再灌注，建立大鼠离体肺缺血再灌注损伤模型6。 关键词:实验,研究,初步,损伤,灌注,缺血,医学论文,