血管紧张素Ⅱ及其受体拮抗剂对胎粪诱导肺损伤中炎症反应的作用

Effects of angiotensin Ⅱ and its receptor inhibition on inflammatory injuries in meconium-exposed S-D rat lungs

目的:研究胎粪吸入所致肺炎症损伤与血管紧张素Ⅱ(AngⅡ)两者之间的相关性及AngⅡ受体拮抗剂的抗炎作用。方法:30只S-D大鼠,随机分为生理盐水对照组、胎粪吸入组和拮抗剂治疗组,每组10只。模型制备后24h取材,观察其肺组织病理损伤并检测湿/干重比及进行病理评分;检测AngⅡ在肺组织的表达情况及用图像分析方法检测其含量;测定肺组织中肿瘤坏死因子-α(TNF-α)的含量及肺匀浆髓过氧化物酶(MPO)活性。结果:胎粪组肺组织病理损伤严重,病理评分及湿/干重比较对照组和治疗组明显增加(P<0.05),对照组和治疗组差异无显著意义;各组间AngⅡPU值、TNF-α含量及MPO活性差异有显著性(P<0.01);并且各组中TNF-α含量及MPO活性与其肺组织中AngⅡPU值呈显著正相关(P<0.01),相关系数分别为0.744和0.747。结论:AngⅡ可增加胎粪吸入肺损伤中炎症因子和炎症细胞含量。受体拮抗剂沙拉欣的治疗可以减轻炎症反应导致的肺损伤。

Objective To investigate the correlations between the inflammatory injuries and the expression of angiotensin Ⅱ （Ang Ⅱ ） in the meconium-exposed rat lungs, as well as the anti-inflammation effects of the unspecific Ang Ⅱ receptor inhibitor saralasin on lung injury. Methods 30 Sprague-Dewley rats were randomized into three groups：（1）saline instilled control rats; （2）meconium-instilled rats; （3）saralasin-pretreated and then meeonium-instilled rats. These animals were killed after 24 hours of treatments and instillation of meconiums. The measurements included lung tissue wet/dry ratio, lung injury score, the expression and level of Ang Ⅱ , lung myeoperoxidase（MPO） activity and TNF-α level. Results Compared with the saline group and the saralasin-pretreated group, the lung tissue wet/dry ratio and lung injury score were significantly increased in meeonium group （P 〈 0.05）; however, there were no differences between saline group and saralasin-pretreated group. Fourthermore, in each group, there were statistically differences in expression of Ang Ⅱ, lung MPO activity and TNF-α level（P 〈 0.01）. Still, both lung MPO activity （r = 0.747, P 〈 0.01） and TNF-α level（r = 0.744, P 〈 0.01） had a positive-relation with the level of Ang Ⅱ. Conclusions Ang Ⅱ can increase the levels of the inflammatory factors and cells. Ang Ⅱ receptor inhibitor saralasin can reduce the inflammation and injury.