上海交通大学学报(医学版)

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高氧致SD大鼠年龄相关的肺损伤及可能机制

宁巍 1,李静 2,漆秀洁 1,3,许峰 2,方芳 1   

  1. 1. 重庆医科大学附属儿童医院重庆市住院医师规范化培训基地,儿童发育疾病研究教育部重点实验室,儿童发育重大疾病国家国际科技合作基地,儿科学重庆市重点实验室,重庆 400014;2. 重庆医科大学附属儿童医院儿科重症监护病房,重庆 400014;3. 重庆医科大学附属儿童医院急诊科,重庆 400014
  • 出版日期:2016-11-28 发布日期:2016-11-29
  • 通讯作者: 李静,电子信箱:lijingwangyi@126.com。
  • 作者简介:宁巍(1986—),男,硕士生;电子信箱:923911380@qq.com。
  • 基金资助:

    国家自然科学基金(81101442)

Mechanism of age-related hyperoxia-induced lung injury in SD rats

NING Wei1, LI Jing2, QI Xiu-jie1,3, XU Feng2, FANG Fang1   

  1. 1. Chongqing Key Laboratory of Pediatrics, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Training Base of Clinical Resident Standard Training in Chongqing, Children’s Hospital of Chongqing Medical University, Chongqing 400014, China; 2. Department of Pediatric Intensive Care Unit, Children’s Hospital of Chongqing Medical University, Chongqing 400014, China; 3. Department of Emergency Department, Children’s Hospital of Chongqing Medical University, Chongqing 400014, China

  • Online:2016-11-28 Published:2016-11-29
  • Supported by:

    National Natural Science Foundation of China, 81101442

摘要:

目的 ·观察新生鼠和幼鼠高氧肺损伤的异同,并初步探索Rho/Rock信号通路在年龄相关高氧肺损伤中的作用。方法 ·将新生SD大鼠(新生鼠)与3周龄SD大鼠(幼鼠)分为新生鼠空气组、新生鼠高氧组、幼鼠空气组、幼鼠高氧组,建立动物模型直至第14日,统计生存率、体质量变化,取SD大鼠肺组织行病理学检查、损伤程度评分、羟脯氨酸含量测定、SOD与MDA检测,以及ROCK1、p-MYPT1、MYPT1表达的检测。结果 ·①新生鼠高氧组较新生鼠空气组、幼鼠空气组、幼鼠高氧组生存率明显降低,幼鼠空气组与高氧组生存率无明显差异;新生鼠高氧组较空气组、幼鼠高氧组较空气组体质量增长缓慢,且新生鼠高氧组较幼鼠高氧组体质量增长更为缓慢。②新生鼠高氧组、幼鼠高氧组出现肺组织损伤及纤维化改变,且新生鼠较幼鼠更为严重。③新生鼠高氧组较空气组、幼鼠高氧组较空气组MDA含量升高,SOD活力降低;与幼鼠高氧组相比,新生鼠高氧组SOD活力基础值较低且高氧后降低更为明显。④新生鼠高氧组较空气组、幼鼠高氧组较空气组肺组织ROCK1蛋白表达有上升趋势,p-MYPT1蛋白表达增强,且新生鼠高氧组较幼鼠高氧组p-MYPT1蛋白表达增强更为明显。结论 ·高氧肺损伤具有年龄依赖性,新生鼠对高氧耐受力明显弱于幼鼠,与其自身抗氧化能力弱有关;Rho/Rock信号通路活化程度的不同可能在年龄相关高氧肺损伤中发挥重要作用。

关键词: 高氧, 肺损伤, 年龄相关, 超氧化物歧化酶, 氧化应激, Rho/Rock信号通路

Abstract:

Objective · To observe the similarities and differences in neonatal rats and immature rats with hyperoxia-induced lung injury and to preliminary explore the role of Rho/Rock signaling pathway in age-related hyperoxia-induced lung injury. Methods · Sprague-Dawley neonatal rats and immature rats aged 3 weeks were randomly assigned to the neonatal air group, the neonatal hyperoxia group, the immature air group, and the immature hyperoxia group. The changes in survival rate and body mass were statistically observed form the construction of animal model till 14 d. Lung tissues of SD rats were harvested. Pathological examination and injury scoring were performed and hydroxyproline, SOD, MDA, ROCK1, p-MYPT1, and MYPT1 were examined. Results · ① The neonatal hyperoxia group had a significantly lower survival rate than the neonatal air group, the immature air group, and the immature hyperoxia group. There was no significant difference in survival rate between the immature air group and the immature hyperoxia group. The body weight increased slower in the neonatal and immature hyperoxia groups than in the neonatal and immature air groups. The body weight increased slower in the neonatal hyperoxia group than in the immature air group. ② The neonatal hyperoxia group and immature hyperoxia group developed lung injury and fibrosis. The neonatal hyperoxia group was more serious than the immature hyperoxia group. ③ The neonatal and immature hyperoxia groups had higher MDA level and lower SOD activity than the neonatal and immature air groups. The neonatal hyperoxia group had lower SOD activity than the immature hyperoxia group. The SOD activity was significantly decreased after hyperoxia treatment. ④ The neonatal and immature hyperoxia groups had higher ROCK1 and p-MYPT1 expressions than the neonatal and immature air groups. The neonatal hyperoxia group had higher p-MYPT1 expression than the immature hyperoxia group. Conclusion · Hyperoxia-induced lung injury is age-dependent. Neonatal rats have significantly weaker hyperoxia tolerance than immature rats and this is associated with the weak antioxidant capacity of their own. The degree of activation of Rho/Rock signaling pathway may play an important role in age-related hyperoxia-induced lung injury.

Key words: hyperoxia, lung injury, age-related, SOD, oxidative stress, Rho/Rock signaling pathway