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西地那非对高氧所致肺损伤模型新生鼠的保护作用
作者:胡倩 李海浪 
单位:东南大学附属中大医院,儿科,江苏,南京,210009
关键词:西地那非 高压氧  新生大鼠 
分类号:R-33, R965, R563.9
出版年·卷·期(页码):2008·27·第三期(219-222)
摘要:

目的:观察西地那非对高浓度氧暴露后新生大鼠肺组织形态学改变的影响,并探讨其机制.方法:80只足月新生SD大鼠随机分为空气加生理盐水对照(A)组、空气加西地那非(B)组、高氧加生理盐水对照(C)组和高氧加西地那非治疗(D)组4组.C、D组输入高体积分数氧(FiO2 0.85),B、D组每天予西地那非100mg·kg-1背部皮下注射.在实验第14天观察肺组织病理改变、放射状肺泡计数(RAC),并且用免疫组化法测定肺组织内皮型一氧化氮合酶(eNOS)蛋白水平.结果:D组肺组织病理改变减轻,RAC和肺微血管数目高于C组(7.340±0.620 vs 5.013±0.738,P<0.001;3.855±0.717 vs 2.375±0.705,P<0.001),且B、D两组肺组织eNOS表达明显增加(均P<0.001).结论:西地那非对高氧所致肺损伤具有一定的保护作用,其机制可能与西地那非降低肺内血管压力及促进肺微血管生成并增加eNOS的表达有关.

Objective To investigate the protective effects of sildenafil treatment on histopathologic changes seen in hyperoxia induced lung injury.Methods Eighty term neonatal Sprague-Dawley(SD) rats were randomly assigned into four group:air-exposed control group,air-exposed+sildenafil-treated group,hyperoxia-exposed control group,and hyperoxia-exposed+sildenafil-treated group.The air control group was exposed to air(FiO2=0.21).The hyperoxia-exposed groups were continuously exposed to hyperoxia(FiO2=0.85).The sildenafil-treated group received sildenafil(100 mg·kg-1) subcutaneously everyday.On the 14th day postnatal,radical alveolar counts(RAC),microvessel count were performed,and lung morphology was studied.Their lungs were examined for immunohistochemical staining of endothelial nitric oxide synthase(eNOS).Results Treatment of hyperoxia-exposed rats with sildenafil resulted in a significant increase in the number of RAC(7.340±0.620 vs 5.013±0.738,P&lt;0.001),the microvessel count(3.855±0.717 vs 2.375±0.705,P&lt;0.001) and eNOS immunostaining in comparison with hyperoxia-exposed placebo-treated animals.Conclusion Treatment with sildenafil during hyperoxia exposure is associated with improved alveolar structure.Treatment of preterm infants with sildenafil may reduce the risk of developing bronchopulmonary dysplasia.The endogenous NOS may play a joint role.

参考文献:

[1] SHEKERDEMIAN L S, RAVN H B, PENNYD J. Intravenous sildenafil lowers pulmonary vascular resistance in a model of neonatal pulmonary hypertension. 2002(8)
[2] 刘雪雁, 吴捷, 薛辛东. 高氧致新生鼠肺损伤时肾组织一氧化氮及氧自由基的变化. 中国当代儿科杂志2005(1). doi:10.3969/j.issn.1008-8830.2005.01.020
[3] ICHINOSE F, ERANA-GARCIA J, HROMI J. Nebulized sildenafil is a selective pulmonary vasodilator in lambs with acute pulmonary hypertension. 2001(5). doi:10.1097/00003246-200105000-00024
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