摘要
目的观察高氧致慢性肺疾病(CLD)新生大鼠肺组织ACE,AngⅡ和ColⅠ蛋白及mRNA含量的动态变化,以探讨卡托普利的保护作用及机制。方法足月新生Wistar大鼠240只,随机分为高氧组、空气对照组、卡托普利治疗组和盐水对照组,每组各60只。将高氧组、盐水对照组和卡托普利治疗组的足月新生Wistar大鼠(连同母鼠)生后即置于氧舱内持续吸入高浓度氧(FiO2=0.9)21 d造成高氧肺损伤模型,空气对照组吸入空气。卡托普利治疗组于生后7 d每天经胃管灌服卡托普利每日30 mg/kg,盐水对照组每天经胃管灌服等量生理盐水。每组分别于实验开始后第1,3,7,14,21天随机选取6只麻醉后处死。肺组织采用ELISA法测定ColⅠ蛋白含量,用日产7170全自动生化分析仪测定ACE活性,用放免法测定AngⅡ的含量。用RT-PCR法检测肺组织ACE,AngⅡ,ColⅠmRNA表达的动态变化并同时观察肺组织形态学变化。结果与空气对照组比较,高氧组、盐水对照组肺组织ACE,AngⅡ,ColⅠ蛋白含量及mRNA表达在实验后第14天明显升高,第21天达高峰(P<0.05或P<0.01),卡托普利治疗组上述指标与高氧组、盐水对照组比较明显降低(P<0.05或P<0.01),但仍高于空气对照组(P<0.05)。肺组织形态学改变:高氧组、盐水对照组第14天肺组织间质细胞增多,出现纤维化改变。第21天正常肺泡结构消失,肺组织出现严重的纤维化。卡托普利治疗组肺组织纤维化病变明显减轻。结论卡托普利干预抑制了高氧致CLD新生大鼠肺组织ACE,AngⅡ,ColⅠ蛋白含量及mRNA表达,减轻了肺纤维化病变,这可能是卡托普利对高氧肺损伤具有保护作用的机制之一。
Objective This study examined the protein and mRNA contents of angintesin converting enzyme （ACE）, angiotensin Ⅱ （Ang Ⅱ） and type Ⅰ collagen and the changes of lung histomorphology in neonatal rats with hyperoxiainduced chronic lung disease （ CLD ） and investigated the protection of captopril against CLD and the possible mechanism. Methods A total of 240 term neonatal Wistar rats were randomly assigned into air, model, normal saline and captopriltreated groups （n =60 each）. The air group was exposed to room air （FiO2 =0.21 ） immediately after birth. The other three groups were exposed to hyperoxia （ FiO2 = 0.9 ） for 21 days to induce lung injury. The captopril-treated group received eaptopril daily （ 30 mg/kg ） by intragastric administration between the 7th and 21st days of hyperoxia exposure. The normal saline group was administrated with normal saline instead. At each time interval of 1, 3, 7, 14 and 21 days after experiment, six rats of each group were randomly chosen and sacrificed. The protein and mRNA levels of ACE, Ang Ⅱ and type Ⅰ collagen were measured by enzyme-linked immunosorbentassay, radio-immunity technique and RT-PCR. The changes of lung histomorphology were observed under a light microscope. Results The protein and mRNA expressions of ACE, Ang Ⅱ and type Ⅰ collagen increased significantly in the model and normal saline groups on the 14th and peaked on the 21st days of exposure compared with those of the air group （ P 〈 0. 05 or 0. 01 ）. Captopril treatment reduced significantly the protein and mRNA expressions of ACE, Ang Ⅱ and type Ⅰ collagen compared the model and normal saline groups on the 14th and 21st days, although the values were significantly higher than the air group （P 〈 0.05 ）. The histopothologie examination demonstrated broadened lung interstitium and reduced alveolar quantity and lung fibrosis was developed in the model and normal saline groups on the 14th day of exposure. Captopril treatment obviously alleviated the changes of lung histomorphology. Conclusions Captopril can inhibit the protein and mRNA expressions of ACE, Ang Ⅱ and type Ⅰ collagen and alleviate lung fibrosis in neonatal rats with hyperoxia-induced lung injury/CLD. This may contribute to one of the possible mechanisms underlying the protective effects of captopril against lung injury/CLD.
出处
《中国当代儿科杂志》
CAS
CSCD
2007年第2期169-173,共5页
Chinese Journal of Contemporary Pediatrics
基金
国家自然科学基金(编号30440056)
