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

 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。

Effects of imidapril on blood gas,oxidative stress and inflammatory factors in rats with acute lung injury induced by ammonium chloride

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 AngⅡ and 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 AngⅡ and CD54, and the concentrations of TNF-α, IL-6 and MDA also increased significantly (P < 0.01) in model group. Pulmonary edema, inflammation, alveolus 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.