卡立泊来德对缺血-再灌注大鼠肺组织钠氢交换蛋白-1表达及炎症损伤的影响

摘要

目的：探讨缺血-再灌注(IR)对肺钠氢交换蛋白-1(NHE-1)表达的影响,及卡立泊来德(cariporide)预处理能否通过抑制 NHE-1表达减轻肺组织的炎症损伤。方法20枚离体灌注的大鼠肺随机分为四组：对照组(C 组)、IR 组、NHE-1激活剂 LiCl 预处理组(LiCl 组)和 cariporide 预处理+缺血-再灌注组(CIR 组)。再灌注结束后,免疫组化检测肺组织中 NHE-1蛋白表达,HE 染色观察肺组织病理学改变并行病理评分。结果与 C 组和 CIR 组比较,IR 组和 LiCl 组 NHE-1表达明显增加(P <0.05),CIR 组和 C 组差异无统计学意义。IR 组和 LiCl 组肺组织病理切片均观察到明显炎症损伤,病理评分明显高于 C 组和 CIR 组(P <0.05),CIR 组病理评分和 C 组差异无统计学意义。结论离体的 IR 大鼠肺组织,NHE-1表达增加,选择性 NHE-1抑制剂 cariporide 能减轻 IR 导致的肺组织炎症损伤。%Objective To investigate the expression of Na+/H + exchanger isoform-1 (NHE-1) during ischemia-reperfusion (IR)in rat lung tissue and determine whether cariporide preconditioning protects lung from inflammatory injury via inhibiting NHE-1 protein expression.Methods Twenty i-solated perfused lungs were randomly divided into 4 groups:the lungs in control group (group C) were continuously perfused for 120 min;the lungs in group IR were subjected to 30 min perfusion, followed by 60 min ischemia and 30 min reperfusion;in group LiCl preconditioning,the lungs were preconditioned with LiCl for 30 min,then continuously perfused for 90 min;in cariporide precondi-tioning+IR (CIR)group,the lungs were preconditioned with cariporide for 30 min,following 60 min ischemia and 30 min reperfusion.After reperfusion,the NHE-1 protein expression was determined by immunohistochemistry and the histopathologic change and pathology scores were ascertained from HE sections.Results The NHE-1 protein expression in lung tissue in groups IR and LiCl were signifi-cantly increased compared with groups C and CIR (P <0.05),and there was no difference between groups C and CIR.Histological examination revealed marked inflammatory changes in groups IR and LiCl,whereas no significant changes in lungs of groups C and CIR.The pathology score of lung in groups IR and LiCl were higher than that in groups C and CIR (P <0.05),and there was no differ-ence between the last two groups.Conclusion IR results in an increased NHE-1 protein expression in rat isolated perfused lung,and the selective NHE-1 inhibitor cariporide could repress the NHE-1 pro-tein expression,thereby decrease the lung inflammatory injury after IR.