卡立泊来德预处理对肺缺血再灌注损伤的保护作用

发布时间：2018-08-02 09:13

【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30min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120min,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120min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(P0.05)和肺组织病理学评分降低(P0.008);除肺组织病理学评分外(P0.008),HOE组余各项指标均较LPD组改善明显(P0.05),但仍未恢复至Sham组水平(P0.05)。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。
[Abstract]:Objective to investigate the effects of selective Na / H exchange-1 antagonist karipolide preconditioning on lung ischemia-reperfusion injury in rabbits. Methods Twenty-four New Zealand white rabbits were randomly divided into three groups: sham operation group (Sham group), ischemia reperfusion group (IR group), low potassium dextran group (LPD group) and kalipolide group (HOE group) with 6 rabbits in each group. After anesthesia, the free left pulmonary hilum bypassed the blocking zone, and the same amount of saline solution or new organ protection solution containing karipolide was injected into the vein of 30min. Except for the observation of 180 min in the Sham group, the remaining 3 groups were ligated with the left pulmonary hilum for 60 min. The model of lung ischemia-reperfusion injury was established in rabbits after 120 minutes of reopening. Before ligation (i.e. before ischemia period), immediately after ligation (that is, immediately after reperfusion), blood gas of femoral artery was extracted from 1530U 6090 and 120min after reperfusion. After reperfusion, lung water content (lung water), malondialdehyde (malondialdehyde), superoxide dismutase (super oxide dismutase) activity, interleukin-6 (IL-6), tumor necrosis factor- 伪 (TNF- 伪) and the expression of sodium hydrogen transporter 1 (natrium hydrogen exchang1NHE1 were measured in left lung tissue. Lung histopathology was observed. Results compared with IR group, the oxygenation index and SOD activity of lung tissue in LPD group and HOE group were higher than those in IR group. Lung tissue LWCU MDA content, IL-6 content, TNF- 伪 content, NHE1 expression (P0.05) and lung histopathological score (P0.008), except lung histopathology score (P0.008), the other indexes in the Hoe group were significantly improved compared with the LPD group (P0.05), but still did not recover to the level of Sham group (P0.05). Conclusion Kallipolide can reduce the expression of NHE1 protein in order to reduce oxidative stress and inflammation during ischemia-reperfusion, and enhance the ability of tissue anti-oxidation, thus effectively attenuating the lung ischemia-reperfusion injury in rabbits in vivo.
【作者单位】：四川大学华西医院麻醉科;
【基金】：国家自然科学基金(No.30972862)资助
【分类号】：R614

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