高氧致新生大鼠支气管肺发育不良肺成肌纤维细胞分布的变化及意义

目的 观察高氧致新生大鼠支气管肺发育不良(BPD)肺组织α-平滑肌肌动蛋白(α-SMA)表达及胶原的变化,探讨高氧致新生大鼠BPD的发生与成肌纤维细胞的内在联系.方法 将新生大鼠持续暴露在85%高氧环境中,在实验的1、3、7、14、21 d,取左肺组织固定、脱水、石蜡包埋、切片,用于肺组织病理变化观察及α-SMA表达的免疫组织化学检测;右肺-80℃冰冻,用于Ⅰ型胶原(ColⅠ)蛋白和mRNA表达检测.结果 新生大鼠长期高氧暴露可致肺泡简单化,肺泡数目减少,终末气腔扩张,次级隔数目减少,肺泡间隔显著增厚,出现纤维化.高氧暴露14和21 d时,α-SMA在肺泡间隔和肺泡表面表达显著增强,呈条素状分布;但空气组仅在次级间隔的顶端呈点状分布.随高氧暴露时间延长,Col Ⅰ表达增加,并且高氧组肺组织α-SMA表达与Col Ⅰ mRNA表达呈明显正相关(r=0.59,P< 0.05).结论 新生大鼠高氧暴露导致肺损伤符合早产儿BPD的病理改变,成肌纤维细胞分布紊乱可能在BPD的发病过程中起重要作用.

The change of myofibroblast distribution in hyperoxia induced bronchopulmonary dysplasia in newborn rats

Objective To investigate the expression of alpha-smooth muscle actin (α-SMA) and collagen Ⅰ in lung tissue of newborn rats with hyperoxia induced bronchopulmonary dysplasia(BPD) and to explore the relationship between the myofibroblast and BPD. Methods Neonatal rats were exposed to room air or 85% oxygen for 21 days. Six rats of both groups were sacrificed at day 1,3,7,14 and 21. The left lung tissues were fixed, the right lung tissues were stored at - 80 ℃. The pathologic changes of lung were observed under optical microscope. Distribution of α-SMA in the lung were determined by immonohistochemical method. The protein and mRNA levels of collagen Ⅰ were detected by ELISA and RT-PCR respectively. Results Prolonged exposure to hyperoxia could result in secondary septum decreasing, enlarging terminal air space and increased collagen deposition in lung tissue. In hyperoxia group,α-SMA expression increased significantly in smooth muscle,alveolar septa interstitium and the surface of alveolar on day 14 and 21. But in air group,α-SMA expressed mainly at the tip of the secondary septa except in smooth muscle. Collagen Ⅰ deposition increased with hyperoxia exposure time prolonged. There was positive correlation between the expression of α-SMA and collagen Ⅰ mRNA in the lung tissue of hyperoxia group. Conclusion The pathological changes of lung injury induced by hyperoxia exposure in newborn rats are consistent with BPD of newborn infant. Abnormality of myofibroblast distribution may play an important role in pathogenesis of BPD.