卡立泊来德预处理减轻离体大鼠肺热缺血再灌注损伤机理的研究  

Cariporide Pretreatment Attenuated Warm Ischemia/Reperfusion Injury in an isolated Rat Lung:A Study on Antioxidative Mechanism

作　　者：刘馨烛[1] 李美亭[1] 周荣华[1] 余海[1] 周棱[1] 李茜[1] 刘斌[1] 

机构地区：[1]四川大学华西医院麻醉科,成都610041

出　　处：《生物医学工程学杂志》2010年第1期132-137,共6页Journal of Biomedical Engineering

基　　金：国家自然科学基金资助项目(30571785)

摘　　要：探讨选择性Na+/H+交换抑制剂卡立泊来德预处理对离体大鼠肺热缺血/再灌注损伤(WI/RI)的保护机理。建立离体大鼠肺灌流模型,30只大鼠随机分为正常对照组(C组)、缺血再灌注组(IR组)和卡立泊来德组(CP组),连续监测平均肺动脉压(mean pulmonary artery pressure,MPAP)和气道峰值(peak airway pressure,pAwP);再灌注结束进行右支气管肺泡灌洗,记录支气管肺泡灌洗液(bronchoaveolar lavage fluid,BALF)回收率(BALF re-covery rate,BALFRR),测定其总蛋白和白蛋白含量;取左肺组织测定肺组织含水量(lung water content,LWC)、超氧化物歧化酶(superoxide dismutase,SOD)活性和丙二醛(malondialdehyde,MDA)含量,并进行肺组织病理学观察。与IR组比较,CP组的BALF总蛋白、肺组织MDA含量、LWC以及再灌注后MPAP明显降低,肺组织SOD活性明显增高,组织病理形态学变化明显减轻。缺血前经离体肺动脉灌注卡立泊来德,可能通过抑制离子耦联机制降低再灌注过程细胞内钙超载,减轻钙依赖的黄嘌呤氧化酶途径的氧自由基释放,同时促进内源性抗氧化途径,增强组织抗氧化能力,从而有效减轻肺热缺血再灌注损伤。This experimental study was designed to explore the possible mechanisms of Cariporide,a kind of Na＋/H＋ exchanger inhibitor,for protecting the lung from warm ischemia/reperfusion injury（WI/RI） of isolated rat lung model.Thirty isolated rat lungs were established on the Langendorff apparatus and randomly divided to three groups（n=10,each）：control group（C group）,ischemia/reperfusion group（IR group） and Cariporide group（CP group）.Mean pulmonary artery pressure（MPAP） and peak airway pressure（pAwP） were monitored continuously.At the end of reperfusion,right bronchoalveolar lavage was performed,bronchoalveolar lavage fluid（BALF） recovery rate （BALFRR） was recorded,and protein content in BALF was measured.Lung water content（LWC）,malondialdehyde（MDA）and superoxide dismutase（SOD）of left lung tissue were measured;histomorphology evaluation was performed under light microscope and transmission electron microscope.In comparison with the data from IR group,BALF protein concentration,LWC,MDA content and MPAP content of reperfusion were significantly decreased,but SOD activity was increased in CP group.Histomorphologic feature also showed that pathological change significantly reduced in CP group.In this rat WI/RI model,the mechanism by which the selective Na＋/H＋ exchanger inhibitor（Cariporide） attenuates lipid peroxidation induced by WI/IR may be： preventing Ca^2＋ overload via inhibiting the transport of Na＋/H2 exchanger-1（NHE1） in the context of the coupled exchanger,thereby reducing the activation of xanthine oxidase pathway and oxygen free radical liberation which is dependent on certain intracellular Ca2＋ concentration,and lastly promoting the endogenous antioxidative mechanism.

关 键 词：Na+/H+交换 卡立泊来德 肺 热缺血再灌注损伤 

分 类 号：R965[医药卫生—药理学]