摘要
目的探讨神经源性肺水肿（NPE）发生时血管紧张素（Ang）Ⅱ系统的变化，以及血管紧张素转换酶抑制剂对于NPE的干预作用。
Objective Neurogenic pulmonary edema （ NPE ） was indicative of poor prognosis in the epidemic of enterovirus 71 infections. The pathogenesis of NPE remains poorly understood. The objectives of this experimental study were to explore whether RAS is activated during NPE in rabbit models induced by fibrin and the effects of an angioteusin converting enzyme inhibitor （enalaprilat） on NPE. Method NPE models were induced by intracisternal injection of fibrinogen and thrombin. According to random number table method, 18 healthy adult New Zealand rabbits were assigned to three groups （with 6 in each）： normal control group （Con group）, NPE group and enalaprilat treated （Ena） group. After establishment of NPE models, rabbits in Ena group were given intravenous enalaprilat 0. 5 mg/kg.Expression of ACE, ACE2, AT1R mRNA of the lung tissue were evaluated by real-time polymerise chain reaction; and Ang I1 of the lung tissue was determined by enzyme linked immunosorbent assay （ ELISA ）. Meanwhile, histopathological lung injury scores were evaluated. Result ACE mRNA expression level in NPE group （ 17. 2 ±3.3） appeared an increasing trend in contrast to Con group （ 12. 6 ±5.2 ） and Ena group （ 11.5 ± 2.4, both P 〉 0. 05 ）. Compared with Con group （81 ±22 ） , ACE2 mRNA expression levels of NPE group （ 52±6 ） and Ena group （ 45±13 ） both decreased （ both P〈0.05 ） . ACE mRNA/ACE2 mRNA expression levels of NPE group （ 0. 33 ±0. 06 ） and Ena group （ 0. 26 ± 0. 04 ） were higher than those of Con group （ 0. 16 ±0. 05, both P 〈0. 05 ）, as well as the ratio of Ena group decreased compared with untreated NPE group （ 0.26 ±0.04 vs. 0.33 ±0.06, P 〈0.05 ） . There were no statistically significant differences in expression of AT1 mRNA of the lung tissue among three groups, but Ena group （ 4. 8 ± 1.1 ） in contrast to NPE group （ 6. 7 ± 1.3 ） has no significant difference （P 〉 0. 05 ）. Lung Ang II level of NPE group [ （ 540 ± 147 ） pg/ml ] was significantly higher than that of Con group [ （253 ± 37 ） pg/ml ] and Ena group [ （ 309 ±35 ） pg/ml, both P 〈 0. 05 ]. Gross pathologic examination showed that pink foamy edema fluid appeared in the tracheal tubes in NPE group, but spontaneously appeared in neither Con group nor Ena group ; and the level of pulmonary subpleural bleeding in Con group, 12 graded 0; in NPE group, 2 graded II , 10 graded m ; in Ena group, 2 graded, 8 grade 11 , 2 grade m. The histopathologic lung injury scores in Ena group was decreased in contrast to NPE group （ 1.36 ± 0. 26 vs. 2. 32 ± 0.49, P 〈 0. 05 ） and mainly for the improvement of alveolar overdistension and interstitial edema. Conclusion The present study showed that when NPE occurs, a high lung Ang 11 concentration was associated with an imbalance between ACE mRNA to ACE2 mRNA expression level. Activated local RAS in lung tissue resulted in lung injury. Enalaprilat treatment may attenuate lung injury by interventing local RAS in lung tissue with decreased ratio of ACE mRNA to ACE2 mRNA and lung Ang 11 concentration. The result will be significant for the angiotensin converting enzyme inhibitor used in the theatment of NPE.
出处
《中华儿科杂志》
CAS
CSCD
北大核心
2014年第8期602-606,共5页
Chinese Journal of Pediatrics
基金
复旦大学上海医学院青年骨干科研启动基金项目（10L19）
国家临床重点专科建设项目一儿科重症重点实验室项目（卫办医政函[2011]872号）
