目的 观察卡托普利对高氧致新生大鼠肺组织纤维化的保护作用.方法 足月新生Wistar大鼠240只,随机分为模型组、空气对照组、治疗组和盐水对照组,每组各60只.模型组、盐水对照组和治疗组将足月新生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;治疗组于生后7 d每天经胃管灌服卡托普利30 mg/(kg·d)(用生理盐水配成5.4 mg/ml混悬液),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的第1、3、7、14、21夭随机选取6只麻醉后处死.肺组织采用酶联免疫吸附法(ELISA)测定Ⅲ型胶原的含量,用放射免疫法测定血管紧张素Ⅱ(AngⅡ)的含量.用逆转录聚合酶链反应(RT-PCR)检测肺组织AngⅡ、Ⅲ型胶原mRNA表达的动态变化,同时观察肺组织形态学变化.结果 模型组及盐水对照组肺组织AngⅡ、Ⅲ型胶原含量及mRNA表达第14天明显升高,除盐水对照组的AngⅡmRNA表达升高不明显外,与空气对照组比较差异均有显著性(P<0.05);两组各项指标在第21天达到高峰,模型组肺组织AngⅡ、Ⅲ型胶原含量分别为(838.22±197.75)、(104.21±43.37)ng/mg,与空气对照组比较差异有显著性(P均<0.01);盐水对照组肺组织AngⅡ、Ⅲ型胶原含量分别为(759.97±60.81)、(128.69±54.74)ng/mg,与空气对照组比较差异有显著性(P均<0.05).治疗组第21天AngⅡ、Ⅲ型胶原含量分别为(554.52±59.32)、(39.90±13.45)ng/mg.其mRNA表达分别为1.50±0.84、1.13±0.55,均明显低于模型组及盐水对照组(P均<0.05),但仍高于空气对照组(P均<0.05).肺组织形态学改变:空气对照组为正常肺组织.模型组、盐水对照组第1天同空气对照组,第3～7天肺泡壁毛细血管扩张,肺间隔水肿,肺间隔及肺泡腔内有中性粒细胞浸润,第14天部分肺泡腔变狭长,肺间隔增宽,肺间质细胞增多,出现肺组织纤维化改变.第21天正常肺泡结构消失,残留肺泡直径明显缩小,肺组织出现严重的纤维化.治疗组肺组织纤维化病变明显减轻.结论 卡托普利对高氧所致肺损伤具有一定的保护作用.%Objective To observe the dynamic changes and the effects of Captopril on interstitial fibrosis in lung tissue of neonatal rats with lung fibrosis induced by hyperoxia. Methods Two hundred and forty neonatal Wistar rats were randomly assigned into model group, air control group, normal saline control and Captopril-trcated group (n=60 each).The air control group was exposed to room air (FiO2 = 0.21), and the rest three groups were continuously exposed to hyperoxia (FiO2 = 0.9) for 21 days. During the exposure, the Captopril-treated group received Captopril [ 30 mg/( kg·d) ] by intragastric administration, and the normal saline control group was administrated with normal saline instead, the model group did not receive any treatment. On the 1 st, 3 rd, 7 th, 14 th and 21 st day of exposure, the subjects were sacrificed. And then, the protein levels of collagen Ⅲ (Co-Ⅲ ) were measured by enzyme-linked immunosorbent assay and angiotensin Ⅱ(Ang Ⅱ )by radio-immunity technique, and the mRNA expression of Ang Ⅱ, Co- Ⅲ was measured by RT-polymerase chain reaction. The changes of lung histomorphology were observed. Results On the 14 th day, The Ang Ⅱ, Co- Ⅲ protein levels and their mRNA expression of modal group and normal saline control group increased significantly as compared to the air control group ( P < 0.05 ), except the Ang Ⅱ mRNA expression of normal saline control group. The Ang Ⅱ and Co-Ⅲ protein levels of model group was (838.22 ± 197.75 ) and ( 104.21 ± 43.37) ng/mg respectively, and normal saline control group was ( 759.97 ± 60.81 ) and ( 128.69 ± 54.74) ng/mg respectively on the 21 st day, their mRNA expression of two groups also increased to the peak on the 21 st day(P< 0.05).The AnglI and Co- Ⅲ protein levels of Captopril-treated group was (554.52 ± 59.32) and (39.90 ± 13.45) ng/mg on the 21 st day respectively, their mRNA expression was (1.50 ± 0.84 ) and (1.13 ± 0.55) respectively, and decreased significantly as compared to the model group and normal saline control group respectively (P<0.05), but increased significantly as campared to the air control group (P < 0.05). The histopathological examination demonstrated different degrees of alveolitis, broaden interstitium and reduced alveolar quantity in the model group and normal saline control group compared with air control group. The pathological changes were markedly alleviated in the Captopril-treated group. Conclusion Captopril may have protective effects on lung injury induced by hyperoxia.
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