咪达普利对氯化铵所致急性肺损伤大鼠血气、MDA及 AngⅡ、CD54蛋白表达的影响

摘要

AIM:In this study, the rat lung injury model was induced by ammonium chloride for studying the effect of imidapril on blood gas, serum TNF-α, IL-6 and MDA concentrations, and AngⅡand CD54 protein expression in rat lung tissue.METHODS:Male rats were randomly divided into 3 groups:control group, lung injury model group and drug group.The rats in control group were given saline (2 mL/kg), while the rats in lung injury model group were given 6% ammonium chloride (2 mL/kg).In drug group, imidapril (3 mg· kg-1· d-1) was given to the rats once daily for 1 week by intragastric gavage after given 6%ammonium chloride.On the 7th day, the rats were anesthetized with 2% so-dium pentobarbital.Abdominal aorta blood, venous blood and lung tissue were collected.The blood gas indexes and serum TNF-α, IL-6 and MDA concentrations were determined.The lung tissues were fixed and sliced, and the expression of AngⅡ and CD54 proteins was detected by immunohistochemistry.RESULTS: The PaCO2 increased in lung injury model group compared with control group and drug group (P<0.05).The expression of AngⅡand CD54, and the concentrations of TNF-α, IL-6 and MDA also increased significantly ( P<0.01) in model group.Pulmonary edema, inflammation, alveo-lus congestion, hemorrhage and hyperplasia in model group were obvious compared with control group and drug group. CONCLUSION:Imidapril improves blood gas indexes, and reduces lipid peroxidation and inflammatory responses in the rats with lung injury induced by ammonium chloride.%目的：本研究通过复制氯化铵致大鼠肺损伤模型，研究咪达普利对肺损伤大鼠动脉血气、MDA、肺形态学和AngⅡ、CD54蛋白表达的影响。方法：将30只雄性大鼠随机分为3组：空白对照组、肺损伤模型组和药物组。对照组大鼠腹腔注射生理盐水2 mL／kg；肺损伤模型组大鼠腹腔注射等量6％氯化铵；药物组大鼠在注射6％氯化铵后，每天1次灌胃咪达普利（3 mg／kg），连续灌胃7 d；在实验第7天，用2％的戊巴比妥钠麻醉，采集腹主动脉血和腹腔静脉血样本；肺组织经4％多聚甲醛灌注、固定、脱水、透明、浸蜡、包埋和切片。 ELISA法测定血清TNF-α和IL-6水平，化学发光法测定血清MDA含量，HE染色观察肺部形态学变化，免疫组织化学染色法观察肺组织AngⅡ和CD54蛋白表达。结果：与对照组相比，模型组PaCO2明显升高（ P＜0.05），血清TNF-α、IL-6和MDA浓度显著增加（ P＜0.01），氯化铵腹腔注射的肺损伤模型组大鼠出现肺水肿、肺炎、肺泡壁瘀血、肺泡腔出血和肺泡壁增生等损伤，肺组织AngⅡ和CD54蛋白表达明显增高（ P＜0.01）；与模型组比较，药物组PaCO2明显降低（ P＜0.05），血清TNF-α、IL-6和MDA浓度以及肺组织AngⅡ、CD54蛋白表达显著降低（P＜0.01）。结论：咪达普利可显著改善氯化铵所致肺损伤大鼠血气，抑制脂质过氧化和血清炎症细胞因子，降低肺组织AngⅡ和CD54蛋白表达。