促红细胞生成素预先给药对大鼠内毒素性急性肺损伤的影响

Effects of erythropoietin pretreatment on acute lung injury induced by lipopolysaccharide in rats

目的探讨促红细胞生成素（EPO）预先给药对大鼠内毒素性急性肺损伤的影响。方法成年雄性SD大鼠32只，体重180～220g，随机分为4组（n=8），C组腹腔注射生理盐水4ml／kg（EPO溶剂对照），50min后静脉注射生理盐水2ml／kg[脂多糖（LPS）溶剂对照]；EPO组腹腔注射EPO3000U／kg，30min后静脉注射生理盐水2ml／kg；LPS组腹腔注射生理盐水4ml／kg，30min后静脉注射LPS6mg／kg；EPO＋LPS组腹腔注射EPO3000U／kg，30min后静脉注射LPS6ms／kg。于静脉注射LPS后4h时处死大鼠，观察肺组织病理学结果，计算肺组织湿／干重（W／D）比；测定肺组织髓过氧化物酶（MPO）活性和丙二醛（MDA）、一氧化氮（NO）含量；采用Westernblot法测定肺组织诱导型一氧化氮合酶（iNOS）和硝基酪氨酸（NT）的表达。结果与C组相比，LPS组和EPO＋LPS组肺组织W／D比、MPO活性、MDA和NO含量升高，iNOS和NT表达上调（P〈0．01）；与LPS组相比，EPO＋LPS组肺组织W／D比、MPO活性、MDA和NO含量降低，iNOS和NT表达下调（P〈0．01）。结论EPO预先给药可减轻大鼠内毒素性急性肺损伤，与其下调iNOS表达，减少NO生成有关。

Objective To investigate the effects of erythropoietin （EPO） pretreatment on the acute lung injury induced by lipopolysaccharide （LPS） in rats and the underlying mechanism. Methods Thirty-two male SD rats weighing 180-220 g were randomly divided into 4 groups （ n = 8 each） ： group Ⅰ control （C） ; group Ⅱ EPO; group. Ⅲ LPS and group Ⅳ EPO ＋ LPS. EPO 3 000 U/kg was given IP in group Ⅱ , LPS 6 mg/kg was given iv in group Ⅲ . In group Ⅳ EPO 3 000 U/kg was given IP at 30 min before iv LPS 6 mg/kg. The animals were killed at d h after LPS administration. Lung tissue specimens were obtained for microscopic examination. Wet/dry ratio （W/D）, myeloperoxidase （MPO） activity, malondialdehyde （MDA） and nitric oxide （NO） content in lung tissue were determined. The expression of inducible nitric oxide synthase （iNOS） and nitrotyrosine （NT） in lung tissue was determined by Western blot. Results W/D ratio, MPO activity, MDA and NO content were significantly increased and iNOS and NT expression was significantly up-regulated in LPS group as compared with control group. EPO pretreatment significantly attenuated the LPS-induced changes in group EPO ＋ LPS. Conclusion EPO pretreatment can ameliorate the acute lung injury induced by LPS by down-regulating iNOS expression and reducing NO production.