卡立泊来德预处理对肺缺血再灌注损伤的保护作用

Cariporide Pretreatment Attenuates Lung Ischemia-Reperfusion Injury in Rabbits

中文关键词:  Na⁺/H⁺交换 卡立泊来德 肺缺血再灌注损伤

英文关键词:Na⁺/H⁺ exchanger Cariporide Lung ischemia-reperfusion injury

中文摘要:

      目的 探讨选择性Na⁺/H⁺交换-1拮抗剂卡立泊来德预处理对兔肺缺血再灌注损伤的作用。方法 将24只新西兰大白兔随机分为假手术组（Sham组）、缺血再灌注组（IR组）、低钾右旋糖酐组（LPD组）和卡立泊来德组（HOE组），每组6只。麻醉后开胸，游离左肺门绕过阻断带，分别于30 min内经静脉泵入等量生理盐水、LPD液或含卡立泊来德的新型器官保护液，除Sham组观察180 min外，余3组均结扎左肺门60 min后，再开放观察120 min，建立在体兔肺缺血再灌注损伤模型。于结扎前（即缺血期前），开放即刻（即再灌注即刻），再灌注后15、30、60、90和120 min分别抽取股动脉血进行血气分析。再灌注结束后取左肺组织测定肺含水量（lung water content，LWC）、丙二醛（malondialdehyde，MDA）含量、超氧化物歧化酶（super oxide dismutase，SOD）活性、白细胞介素-6（interleukin-6，IL-6）含量、肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）含量和钠氢转运体-1（natrium hydrogen exchanger-1，NHE1）表达量，并进行肺组织病理学观察。结果 同IR组相比，LPD组和HOE组氧合指数（再灌注开始后）和肺组织SOD活性升高，肺组织LWC、MDA含量、IL-6含量、TNF-α含量、NHE1表达量（P<0.05）和肺组织病理学评分降低（P<0.008）；除肺组织病理学评分外（P>0.008），HOE组余各项指标均较LPD组改善明显（P<0.05)，但仍未恢复至Sham组水平（P<0.05）。结论 卡立泊来德可通过减少NHE1蛋白表达以减轻缺血再灌注期间氧化应激和炎症反应，并同时增强组织抗氧化能力，从而有效减轻在体兔肺缺血再灌注损伤。

英文摘要:

      Objective To explore the effects of selective Na⁺/H⁺ exchanger antagonist Cariporide on ischemia-reperfusion induced lung injury. Methods Twenty four New Zealand White rabbits with lung ischemia-reperfusion model were established and randomly divided into four groups (n=6 per group) including sham group (S group), ischemia-reperfusion group (IR group), low potassium dextran group (LPD group) and Cariporide group (HOE group). Blood and lung tissue samples were obtained for blood gas, biochemical analyses and histologic examination. Results Systemic administration of HOE increased oxygenation index (arterial oxygen tension/fraction of inspire oxygen, PaO₂ /FiO₂ ) and superoxide dismutase （SOD） activities, while decreased malondialdehyde （MDA） contents, proinflammatory cytokines and natrium hydrogen exchanger-1 （NHE1） expressions, along with the reduction of lung water content （LWC） except for histologic evaluation scores (P<0.05, versus IR group and LPD group). Conclusion Systemic administration of Cariporide before ischemia could protects the lung from ischemia-reperfusion injury via decreasing NHE1 expression. The protective effect seems to be closely related to regulating intracellular calcium overload, oxidative damage and antioxidant enzyme activities and neutrophil infiltration.