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目的明确高氧暴露新生大鼠肺组织的肺泡间隔增厚是否由肺泡间隔细胞凋亡抑制引起,进一步研究茶碱是否可以通过减少肺泡间隔厚度改善高氧暴露新生大鼠的肺发育。方法建立新生SD大鼠高氧暴露(85%O2)肺损伤模型,将新生大鼠随机分为3组。①新生大鼠每日注射生理盐水并予高氧暴露;②新生大鼠每日注射生理盐水并置正常空气中;③新生大鼠注射茶碱20 mg/(kg.d)并予高氧暴露。并运用TUNEL法检测肺泡间隔中的凋亡细胞,用免疫组织化学技术检测肺泡间隔中的肌成纤维细胞。结果高氧暴露7 d的新生大鼠肺组织肺泡间隔增厚,肺泡间隔细胞凋亡减少,肺泡间隔肌成纤维细胞数量增加;而茶碱可以使高氧暴露后新生大鼠肺组织肺泡间隔细胞变薄,肺泡间隔细胞凋亡增加,肺泡间隔肌成纤维细胞减少。结论茶碱可以通过减少肺泡间隔厚度,减少肺泡间隔内的肌成纤维细胞数量,进而改善高氧暴露新生大鼠的肺发育。增加肺泡间隔细胞凋亡可能是茶碱的作用机制之一。肌成纤维细胞作为一种重要的间质细胞,可能在高氧引起的肺泡间隔细胞凋亡异常及肺泡间隔增厚等变化中起重要作用。[临床儿科杂志,2010,28(12):1101-1107]
Objective To investigate whether alveolar septum thickening induced by hyperoxia exposure in lung tissue of neonatal rats is caused by the inhibition of apoptosis of alveolar septum cells. To further investigate whether theophylline can improve the lung development of neonatal rats exposed to hyperoxia by reducing the thickness of alveolar septa. Methods The model of lung injury in neonatal SD rats exposed to hyperoxia (85% O2) was established. The neonatal rats were randomly divided into three groups. (1) Neonatal rats were injected with saline daily for hyperoxia exposure; (2) Neonatal rats were injected with normal saline daily and placed in normal air; (3) Neonatal rats were injected with 20 mg / (kg.d) theophylline for hyperoxia exposure . Apoptotic cells in the alveolar septum were detected by TUNEL method and myofibroblasts in the alveolar septum were detected by immunohistochemistry. Results In neonatal rats exposed to hyperoxia, thickened alveolar septum, reduced apoptosis of alveolar septa cells and increased number of alveolar septum myofibroblasts in neonatal rats exposed to hyperoxia; while theophylline increased the number of pulmonary alveolar septa cells Thinning, alveolar septum increased apoptosis, decreased alveolar septum myofibroblasts. Conclusion Theophylline can improve the lung development of neonatal rats exposed to hyperoxia by reducing the thickness of the alveolar septum, reducing the number of myofibroblasts in the alveolar septum. Increased alveolar septa cell apoptosis may be one of the mechanisms of theophylline. As an important interstitial cell, myofibroblasts may play an important role in the abnormal apoptosis of alveolar septum caused by hyperoxia and alveolar septum thickening. [Journal of Clinical Pediatrics, 2010,28 (12): 1101-1107]