重组人类促红细胞生成素对早产大鼠高氧肺损伤的影响

Effect of Recombinant Human Erythropoietin on Hyperoxia Induced Lung Injury in Premature Rats

摘要:

目的:探讨重组人类促红细胞生成素(rhEpo)对早产大鼠高氧肺损伤的影响。方法:生后 3 d的早产鼠随机分为Ⅰ.空气对照组，Ⅱ.高氧对照组，Ⅲ.高氧+rhEpo组，Ⅳ.空气+rhEpo组。高氧组持续暴露于 ≥90%氧(O2)中，rhEpo 组自生后 3 d开始皮下注射 rhEpo 800 U/kg，隔日1次。分别于暴露3 d，7 d检测各组支气管肺泡灌洗液(BALF)中还原型谷光甘肽(GSH)、总蛋白、丙二醛(MDA)、非血红素铁含量，并比较肺湿重/干重(W/D)及肺组织病理改变。结果:①与空气组相比，高氧组高氧3 d时 MDA 含量显著增加［(1.39±0.60) nmol/ml vs (0.35±0.22) nmol/ml］(P<0.01)；肺组织呈急性肺损伤病理改变。与空气组比较，高氧组7 d时非血红素铁、MDA、总蛋白含量均显著升高［(109.31±7.86) μg/dl vs (94.95±10.83) μg/dl，(1.53±0.39) nmol/ml vs(0.30±0.13) nmol/ml，(0.47±0.02) g/L vs (0.25±0.04) g/L］(P<0.01)；肺W/D值升高(5.54±0.41 vs 5.00±0.15)(P<0.05)，肺病理改变加重出现肺纤维化趋势及结构紊乱。②高氧+rhEpo组 3 d时BALF中MDA为(0.69±0.19) nmol/ml；7 d时非血红素铁、MDA、总蛋白含量、肺W/D值分别为(99.60±8.21) μg/dl，(0.80±0.24) nmol/ml，(0.36±0.02) g/L，5.08±0.21，较高氧组显著下降(P<0.05 或 0.01)；3 d，7 d时GSH含量分别为(130.85±7.62) mg/L和(136.69±5.90) mg/L，较高氧组显著升高(P<0.01)。肺病理改变减轻。结论:高氧暴露3 d即可造成早产鼠急性肺损伤，7 d时加重。rhEpo 对早产鼠高氧肺损伤有一定的保护作用。

Abstract:

OBJECTIVE: To investigate the effect of recombinant human erythropoietin (rhEpo) on hyperoxia induced lung injury in premature rats. METHODS: Three dayold premature rats were randomly assigned to four groups: Ⅰ. the room air group, Ⅱ. the hyperoxia group, Ⅲ. the hyperoxia+rhEpo group, Ⅳ. the room air+rhEpo group. Group Ⅰ and Ⅲ rats were exposed to 90% O2. Group Ⅲ and Ⅳ rats received rhEpo (800 U/kg) subcutaneously every other day. After 3 days or 7 days of exposure, the contents of glutathione (GSH), total protein, malondialdehyde (MDA) and nonheme iron in the bronchoalveolar lavage fluid (BALF) and the ratio of lung wet weight/dry weight (W/D), and lung morphometry were examined in all groups. RESULTS: ① After 3 days, Group Ⅱ rats showed an increase of MDA content compared with Group Ⅰ rats ［(1.39±0.60) nmol/ml vs (0.35±0.22) nmol/ml，P<0.01］, and presence of hyperaemia, red cell extravasation and inflammatory infiltration. After 7 days of exposure, the contents of nonheme iron, total protein and MDA increased in Group Ⅱ rats compared with Group Ⅰ rats ［(109.31±7.86) μg/dl vs (94.95±10.83) μg/dl, (1.53±0.39) nmol/ml vs (0.30±0.13) nmol/ml，(0.47±0.02) g/L vs (0.25±0.04) g/L, respectively］, P<0.01. And the ration of lung W/D also increased ［(5.54±0.41) vs (5.00±0.15)］，P<0.05, and pathologic changes were more severe than those after 3 days of exposure. ② After 3 days of exposure, compared with Group Ⅱ rats, MDA content ［(0.69±0.19) nmol/ml］ in Group Ⅲ rats decreased significantly (P<0.01), and the changes of acute lung injury were also alleviated. After 7 days of exposure, the contents of MDA ［(0.80±0.24) nmol/ml］, total protein ［(0.36±0.02) g/L］, nonheme iron ［(99.60±8.21) μg/dl］ and lung W/D (5.08±0.21) also decreased in Group Ⅲ rats compared with Group Ⅱ rats (P<0.01 or 0.05). GSH contents increased in Group Ⅲ rats both after 3 days and 7 days of exposure ［(130.85±7.62) mg/L and (136.69±5.90) mg/L］ compared with those in Group Ⅱ rats ［(106.86±9.87) mg/L, (122.19±10.41) mg/L］(both P<0.01), and pathologic changes in Group Ⅲ rats were alleviated more than those in Group Ⅱ rats. CONCLUSIONS: Exposure to 90% O2 for 3 days and 7 days result in acute lung injury in pretmature rats. Treatment with rhEpo alleviates hyperoxic lung injury in premature rats.