一氧化氮吸入对新生鼠高氧肺损伤时表面活性蛋白A和肺甘露糖结合力的影响

Effect of inhaled nitric oxide on surfactant protein A and mannose binding ability in the lung of neonatal rats with hyperoxia-induced lung injur

摘要:

目的：通过观察吸入一氧化氮(iNO)对新生大鼠高氧肺损伤时表面活性蛋白A(SP-A)和肺组织甘露糖结合力(MBA)的影响,探讨iNO对高氧肺损伤保护作用的可能机制。方法：新生大鼠随机分为对照组(空气);高氧组(>95%O2,6d);NO组(空气+10ppmNO,24h);高氧+NO组(>95%O2,6d+10ppmNO,24h)。观察暴露后2d和6d肺组织病理变化,肺SP-AmRNA基因表达、蛋白含量和MBA的变化。结果：高氧组病理损伤明显,暴露后2d时SP-A的mRNA含量(0.81±0.04vs1.53±0.25)和蛋白表达(59.45±18.37vs89.77±16.41)比对照组减少,6d时分别比对照组增加(0.81±0.02vs0.63±0.03),(93.57±13.71vs47.73±21.69),(P<0.05)。高氧+NO组暴露后2d时病理损伤比高氧组明显减轻,SP-AmRNA(0.55±0.91)比对照组和高氧组降低,SP-A蛋白表达(55.12±17.53)比对照组降低(P<0.01);6d时SP-A蛋白表达(67.33±18.59)比高氧组降低(P<0.05)。甘露糖结合力在暴露后2d时NO组比对照组增加(0.821±0.133vs0.580±0.158)、高氧+NO组比高氧组增加(0.430±0.175vs0.738±0.141)(P<0.05)。结论：小剂量NO吸入可降低高氧肺组织SP-A蛋白表达的升高,增加肺组织的MBA,减轻肺组织的病理损伤。

Abstract:

OBJECTIVE: To investigate the effect of inhaled nitric oxide (NO) on surfactant protein A (SP-A) and mannose binding ability (MBA) in neonatal rats with hyperoxia-induced lung injury. METHODS: Sixty-four neonatal rats were randomly exposed to room air (Control group), >95% oxygen for 6 days (Hyperoxia group), 10 ppm NO for 24 hrs (NO group), and >95% oxygen for 6 days along with 10 ppm NO for 24 hrs (Hyperoxia + NO group). After 2 and 6 days of exposure, the lung pathologic changes, gene and protein expressions of SP-A and MBA were measured. RESULTS: The rats from the Hyperoxia group presented with obvious lung injuries. The SP-A expressions of mRNA (0.81 ± 0.04 vs 1.53±0.25) and protein (59.45 ± 18.37 vs 89.77±16.41) in the Hyperoxia group decreased significantly 2 days after exposure but increased significantly 6 days after exposure (SP-A mRNA 0.81±0.02 vs 0.63 ± 0.03; SP-A protein 93.57±13.71 vs 47.73±21.69) compared with those of the Control group (P<0.05). NO treatment alleviated the hyperoxia-induced pathologic injuries 2 days after exposure. The SP-A mRNA expression (0.55±0.91) in the Hyperoxia + NO group was significantly reduced as compared to both the Control and Hyperoxia groups (P<0.05), and the SP-A protein expression (55.12±17.53) in the Hyperoxia + NO group was noticeably lower than that of the Control group ( P<0.01) 2 days after exposure. The SP-A protein expression in the Hyperoxia + NO group (67.33±18.59) was significantly lower than that of the Hyperoxia group 6 days after exposure (P<0.05). Two days after exposure, the NO group had significantly higher MBA than the Control group (0.821 ± 0.133 vs 0.58 ± 0.158); the Hyperoxia + NO group had significantly higher MBA than the Hyperoxia group (0.43 ± 0.175 vs 0.738 ± 0.141) (P<0.05). CONCLUSIONS: Inhaled low dose NO may decrease SP-A protein expression and increase MBA of the lung tissue. This lessens the pathologic lung injury in neonatal rats with hyperoxia.