不同剂量促红细胞生成素对新生大鼠高氧肺损伤血管保护作用的研究

Effects of different dosage of recombinant human erythropoietin on pulmonary angiogenesis in newborn rats exposed to hyperoxia

目的探讨不同剂量重组人促红细胞生成素（recombinant human erythropoietin，rhVO）作为血管生长样因子对新生大鼠高氧肺损伤的血管保护作用。方法新生Sprague—Dawley大鼠60只，分为空气组、高氧组（持续吸入95％的高浓度氧）、高氧＋大剂量rhEPO组（于高氧暴露前1h及暴露3d后，腹腔注射rhEPO5000U／kg）及高氧＋小剂量rhEPO组（时间点同前，腹腔注射rhEPO800U／埏），每组15只。而空气组和高氧组分别于同一时间点腹腔注射等量生理盐水。高氧暴露6d时，观察各组大鼠存活率变化，免疫组织化学法检测肺组织血管内皮标志CD31及肺血管内皮细胞生长因子（vascu．1arendotheli^growthfactor，VEGF）表达的变化。结果高氧暴露6d后，与高氧组相比，高氧＋大剂量rhEPO组大鼠存活率显著提高[86．7％（13／15）VS60．0％（9／15）]；肺组织CD31阳性面积比[（38．69±1．69）％VS（33．57±4．12）％，P〈0．05]和VEGF的表达（124．4296±7．2823VS114．2059±8．3457，P〈0．05）明显增高；而高氧＋小剂量rhEPO组肺组织CD31阳性面积比[（36．34±1．89）％]及VEGF的表达（115．4296±6．7199）无明显改善，差异无统计学意义（P〉0．05）。结论大剂量rhEPO（5000U／kg）可以促进肺血管的发育和修复，对新生鼠高氧肺损伤有血管保护作用，而800U／kgrhEPO无明显的高氧肺损伤血管保护作用。

Objective To investigate the effect of different dosage recombinant human erythropoie- tin（ rhEPO）, an angiogenesis-like factor, on pulmonary angiogenesis exposed to hyperoxia in newborn rats. Methods Sixty Sprague-Dawley newborn rats were randomly divided into four groups：air group （room air exposure, n = 15 ）, hyperoxia group （ exposed to 95 % oxygen, n = 15 ）, hyperoxia ＋ large dosage rhEPO group （received rhEPO 5 000 U/kg,intraperitoneally on 1 hour before and 3 days after exposed to hyperoxia, n = 15 ） and hyperoxia ＋ small dosage rhEPO group （received rhEPO 800U/kg, the same time points, n = 15 ）. The isodose of saline were given intraperitoneally on the same time points in the air group and the hyperoxia group. After 6 d of exposure, the survival rate was compared, CD31 and vascular endothelial growth factor （VEGF） were measured by immunohistochemistry to assess hyperoxia-induced changes in lung morphology. Results After 6d of exposure,hyperoxia ＋ large dosage rhEPO group prolonged the survival rate in compari- son with the hyperoxia group [ 86. 7% （ 13/15 ） vs 60.0% （9/15） 1- The expression of lung CD31 [ （38. 69 ± 1.69）% vs （33. 57 ±4. 12）% ,P〈0.05] and VEGF （124.4296 ±7.282 3 vs 114.205 9 ±8.345 7,P 〈0. 05） in newborn rats treated with large dosage of rhEPO was significantly higher than those in hyperoxia group. While there was no significant difference of CD31 [ （36. 34 _＋ 1.89）% ] and VEGF（l15.429 6 ±6.719 9）in small dosage rhEPO group compared with the hyperoxia group （P 〉 0. 05 ）. Conclusion Instead of treatment with small dosage rhEPO （800 U/kg） ,large dosage rhEPO （5 000 U/kg） may have important protective effects on pulmonary angiogenesis in hyperoxia-induced lung injury of newborn rats.