卡托普利对急性肺损伤血凝素样氧化低密度血浆脂蛋白受体-1蛋白表达的影响

Captopril suppresses lectin-like oxidized LDL receptor-1 protein in rats after acute lung injury

目的研究大鼠急性肺损伤模型及其卡托普利干预下肺组织血凝素样氧化低密度血浆脂蛋白受体-1(lectin-like oxidized LDL receptor-1,LOX-1)蛋白表达的变化,旨在探讨LOX-1在急性肺损伤中的表现及初步干预措施。方法将30只SD大鼠按随机数字法分成3组:生理盐水对照组、脂多糖组(5mg/kg)和卡托普利治疗组(1.25mg/kg),每组10只。观察各组大鼠动脉血氧分压[p(O2)]、肺湿质量/干质量值(W/D)、支气管肺泡灌洗液(bronchoalveolar lavagefluid,BALF)蛋白含量及肺组织病理变化,利用Westernblot法检测各组大鼠肺组织中LOX-1蛋白的表达。结果脂多糖处理后大鼠的肺部炎症反应显著,以中性粒细胞浸润为主,脂多糖组p(O2)[(6.86±0.75)kPa]较对照组[(12.14±0.60)kPa]下降(P<0.05),脂多糖组肺W/D(7.47±0.31)、BALF蛋白含量(0.39±0.07)g/L、LOX-1蛋白的表达(0.91±0.12)较对照组肺W/D(3.82±0.21)、BALF蛋白含量(0.26±0.05)g/L、LOX-1蛋白表达量(0.38±0.05)升高(P<0.05)。与脂多糖组p(O2)相比,卡托普利治疗组p(O2)[(9.43±0.89)kPa]和肺组织病理变化明显改善,肺W/D(5.21±0.08)、BALF蛋白含量(0.34±0.05)g/L和LOX-1蛋白表达(0.43±0.08)降低(P<0.05)。结论LOX-1蛋白可能参与急性肺损伤过程;卡托普利对急性肺损伤有保护作用,而此作用可能与抑制LOX-1的表达有关。

Objective To study the expression of lectin-like oxidized LDL receptor-1 （LOX-1） protein in acute lung injury （ALI） and the effect of captopril on this expression in order to investigate its role in the process and preliminary intervention.Methods Sprague-Dawley rats were randomly divided into 3 groups,normal control group,lipopolysaccharide （LPS） groups,and a LPS＋captopril group,each group 10 rats.ALI model was induced by intratracheal injection of LPS （5 mg/kg）,then those of LPS＋captopril group were give an intraperitoneal injection of captopril （1.25 mg/kg）.The animals of normal control group received an intratracheal injection of normal saline.In 6 h after LPS injection,the level of p（O2）,wet/dry ratio （W/D）,concentration of total protein in bronchoalveolar lavage fluid （BALF） and lung tissue histopathological changes were examined.The expression of LOX-1 protein in the lung tissue was measured by Western blot analysis.HE staining was used to examine the pathological changes of the lung.Results Histological examination showed that extensive lung inflammation were seen in the LPS group,which manifested by accumulation of significant numbers of neutrophils.The level of p（O2） in LPS group [（6.86±0.75） kPa] was decreased compared with that in sham group [（12.14±0.60） kPa,P0.05].The level of W/D （7.47±0.31）,concentration of total protein in BALF （0.39±0.07） g/L and the expression of LOX-1 protein （0.91±0.12） in LPS group were increased significantly compared with W/D （3.82±0.21）,total protein in BALF （0.26±0.05） g/L and LOX-1 expression of protein in sham group （0.38±0.05） （P0.05）].Compared with LPS group,these changes were markedly attenuated in LPS＋captopril group （P0.05） [W/D （5.21±0.08）,total protein in BALF （0.34±0.05） g/L,and LOX-1 protein expression （0.43±0.08）,and the level of p（O2）（9.43±0.89） kPa] and pathological changes of the lung were also ameliorated in this group.Conclusion LOX-1 protein may be involved in the pathogenesis of ALI.Captopril exerts a protective effect on ALI,which may be through inhibiting the expression of LOX-1 protein.