新生大鼠高氧性肺损伤中HOXB5表达变化及其作用分析

摘要

目的 建立新生大鼠高氧性肺损伤模型,观察高氧性肺损伤过程中HOXB5蛋白表达的变化,探讨其与高氧肺损伤肺的关系,为临床防治高氧性肺损伤提供理论依据.方法 将新生12 h内的SD大鼠60只,随机分为高氧(FiO2为85% ～ 90%)实验组和空气对照组2组,再按生后不同的时间点分为6个亚组,观察两组实验动物的一般情况、肺组织学变化,并检测肺组织中HOXB5基因蛋白表达量.结果 对照组与实验组肺组织中HOXB5蛋白表达在不同时间点均呈现出起伏不定的变化特点,两组呈现相同的变化趋势,但实验组变化时间滞后.两组除生后24 h末和生后21 d 2个时间点表达差异无统计学意义(P ＞ 0.05)外,从生后第3天起及第5、7、14天相应的4个时间点与对照组相比差异有统计学意义(P ＜ 0.01).结论 高氧暴露后新生大鼠肺组织中HOXB5基因蛋白表达变化出现滞后,同时出现支气管分支形成的紊乱和结构简单的肺泡,提示HOXB5基因蛋白异常变化可能是导致高氧慢性肺损伤的原因,HOXB5蛋白可能对支气管和肺泡上皮发育和成熟起调节作用.%Objective To investigate the expressional change of HOXB5 in neonatal Sprague-Dawley rats with hyperoxia-induced lung injury for exploring the correlation of HOXB5 with hyperoxia-induced lung injury and providing the theoretical basis for the management of hyperoxic lung injury.Methods Sixty neonatal SD rats were randomly divided into the air group (exposure of the air) and the hyperoxia group (exposure of the high concentration oxygen with FiO2 of 0.85 - 0.90).The rats were sacrificed at 1, 3, 5, 7, 14 and 21 days after birth for observing the general status of rats, the pathological changes of lung examined by the histopathologic method, and the HOXB5 level detected by the Western blot and immunohistochemical methods, respectively.Results There were obvious pathologic changes in lung tissues in the hyperoxic group after three-day hyperoxic explosure, and the damage was more serious with the longer explosure of hyperoxia.The expression of HOXB5 in normal lung showed the low levels in all time points except for the highest level within 24 hours and the higher level on day 5 after birth.A similar but delayed tendency of the expressional changes was shown in the hyperoxic group.The expressional level of HOXB5 tended to increase since on day 3 after birth, and with the significant differences in the increased level of HOXB5 on day 3, 7 and 14 (P ＜ 0.05 for all), except for an obvious reduced level on day 5 (P ＜ 0.01), compared with those in the air group, respectively.Furthermore, there was no significant differences in HOXB5 level between either the 5th day in the hyperoxia group and the 3rd day in the air group, or the 7th day in the hyperoxia group and the 5th day in the air group (P ＞ 0.05 for all).Conclusions The HOXB5 plays an important role for the development of lung.An abnormal expression of HOXB5 may probably be main reason in the pathogenesis of hyperoxia-induced lung injury.