硝基酪氨酸和诱导型一氧化氮合酶在大鼠胎粪吸入性肺损伤中表达的研究

目的：观察大鼠胎粪诱导肺损伤时肺组织硝基化酪氨酸和诱导型一氧化氮合酶（iNOS）表达的改变，探讨两者在此种损伤中的作用。 方法： 16只雄性SD大鼠，随机分为对照组和胎粪组，分别由气管插管注入生理盐水或20%胎粪生理盐水混悬液1 mL/kg。24 h后取材，观察支气管肺泡灌洗液（BALF）细胞计数，比色法检测肺组织匀浆髓过氧化物酶（MPO）活性、一氧化氮（NO）含量，Western blot法测定硝基酪氨酸和iNOS蛋白表达改变。 结果： 胎粪组BALF细胞计数、肺组织MPO活性、NO含量分别为(4.04±1.01)×109cells/L、(1.49±0.22)U/g wet lung tissue、(12.77±5.00)mmol/g protein，对照组BALF细胞计数、肺组织MPO活性、NO含量分别为(0.53±0.19)×109cells/L、(0.62±0.16)U/g wet lung tissue、(4.89±1.32)mmol/g protein，两组比较差异显著（均P<0.01）；Western blot结果显示胎粪组肺组织硝基酪氨酸和iNOS蛋白表达明显强于对照组，分别为0.46±0.19和1.49±0.60，与对照组（0.15±0.04和0.09±0.04）比较, 差异显著（均P<0.01）。 结论： 胎粪可诱导iNOS表达增强并产生过量的硝基酪氨酸，两者可能在胎粪性肺损伤发病机制中发挥重要作用。

Meconium induces formation of nitrotyrosine and expression of inducible nitric oxide synthase in the rat lung

AIM: To evaluate the contribution of inducible nitric oxide synthase (iNOS) and nitrotyrosine to acute lung injury (ALI) in rats with meconium aspiration. METHODS: 16 health male Sprage-Dawley rats were randomized to control group and meconium group, followed by intratracheally administration of 1 mL/kg saline or 1 mL/kg 20% human newborn meconium suspension. The animals were killed after 24 h of treatment. The measurements included bronchoalveolar lavage fluid (BALF) cell count, pulmonary myoloperoxidase (MPO) activity and nitric oxide (NO) level. Western bloting was used to determine the expression of pulmonary nitrotyrosine-a specific “footprint” of peroxynitrite and iNOS. RESULTS: Compared to control group, the rats in the meconium group had increased BALF cell counts ［(4.04±1.01)×109cells/L vs （0.53±0.19)×109cells/L］, pulmonary MPO activity ［(1.49±0.22）U/g wet lung tissue vs (0.62±0.16) U/g wet lung tissue］, NO level ［(12.77±5.00） mmol/g protein vs （4.89±1.32) mmol/g protein］, increased expression of nitrotyrosine and iNOS (0.46±0.19 and 1.49±0.60 vs 0.15±0.04 and 0.09±0.04, respectively), all P<0.01. CONCLUSIONS: Meconium results in an increase in expression of pulmonary iNOS, leading to over production of NO and nitrotyrosine, which may be of pathogenic importance in the ALI with meconium aspiration.