高氧诱导早产鼠慢性肺疾病肺超微结构变化及氧化应激反应的研究

Changes of ultrastructure and oxidative stress reaction of lungs in premature rats with chronic lung disease induced by hyperoxia

摘要:

目的 慢性肺疾病 (CLD)是早产儿吸入高浓度氧治疗后最常见的并发症 ,目前认为肺部氧化应激反应与CLD的发生密切相关。该文探讨高氧致早产鼠CLD发生中肺组织超微结构及氧化应激反应的动态变化。方法 高浓度氧致早产鼠CLD模型 (实验组 )和正常对照组各 4 0例为研究对象 ,应用分光光度计比色法在实验后1 ,3,7,1 4 ,2 1d动态测定肺组织超氧化物岐化酶 (SOD)活性及脂质过氧化产物丙二醛 (MDA)的含量 ,并同步观察肺组织超微结构的变化。结果 吸高氧后初期 (1～ 3d) ,Ⅱ型肺泡上皮细胞 (AEC Ⅱ )即出现线粒体、板层小体等细胞器的损伤 ;7d后 ,除细胞器结构破坏外 ,开始出现细胞核的异常 ,且随吸氧时间的延长上述改变逐渐加重。实验组肺组织SOD的活性虽逐渐增高 ,但与对照组比较 ,其差异无显著性 (P >0 .0 5 ) ;实验组MDA水平从吸高氧第3天起即明显高于对照组 (5 5 .9± 5 .5nmol/mgvs 2 2 .5± 4 .4nmol/mg) (P <0 .0 1 ) ,7d达高峰 94 .3± 1 2 .4nmol/mg ,持续 1周后逐渐下降 ,2 1d时仍高于对照组 (4 8.0± 7.5nmol/mgvs2 3.6± 5 .7nmol/mg) (P <0 .0 1 )。结论 AEC Ⅱ损伤是高氧诱导CLD的早期特征 ;肺部氧化应激反应与AEC Ⅱ损伤密切相关。

Abstract:

Objective Oxygen therapy is a common means in the treatment of lung disease in premature infants. However, long time inhalation of high concentration of oxygen can induce lung injury, even chronic lung disease (CLD). This paper aims at studying the dynamic changes of lung ultrastructure and oxidative stress reaction in premature rats with hyperoxia induced CLD and in exploring the role of lung oxidative stress reaction in pathogenesis of CLD. Methods Eighty premature rats were randomly assigned into a Hyperoxia group and a Control group (n=40 each). The Hyperoxia group was given a high concentration of oxygen (FiO 2>0.90) and developed CLD. The Control group received oxygen with the FiO 2 of 0.21. The superoxide dismutase (SOD) activity and malondialdehyde (MDA) concentration of the lung were assayed with a spectrophotometer and the lung ultrastructure in the two groups was observed under a transmission electronmicroscope. Results The structures of mitochondria and lamellar bodies in alveolar epithelial cell Ⅱ (AEC Ⅱ) were partly damaged on the 3rd day of hyperoxia induction. The abnormal nuclei developed in addition to the damaged mitochondria and lamellar bodies in AEC Ⅱ after the 7th day. Compared with the Control group, the MDA level in the Hyperoxia group was increased significantly on the 3rd day ( 55.9 ± 5.5 nmol/mg vs 22.5 ± 4.4 mmol/mg) (P< 0.01 ), and it reached a peak on the 7th day ( 94.3 ± 12.4 nmol/mg). After 7 days the MDA level in the Hyperoxia group decreased gradually but still remained at a higher level on the 21st day than that of the Control group ( 48.0 ± 7.5 nmol/g vs 23.6 ± 5.7 nmol/g) (P< 0.01 ). The SOD activity in the Hyperoxia group did not differ from the Control group. Conclusions AEC Ⅱ injury is early manifestation of hyperoxia induced CLD. The lung oxidative stress reaction is closely related to the AEC Ⅱ injury.