Mikolka P, Kopincova J, Tomcikova Mikusiakova L, Kosutova P, Antosova M, Calkovska A, Mokra D
Biomedical Center (BioMed) Martin, Division of Respirology, Jessenius School of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia.
Department of Physiology, Jessenius School of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia.
J Physiol Pharmacol. 2016 Feb;67(1):57-65.
Meconium aspiration syndrome (MAS) is a serious condition, which can be treated with exogenous surfactant and mechanical ventilation. However, meconium-induced inflammation, lung edema and oxidative damage may inactivate delivered surfactant and thereby reduce effectiveness of the therapy. As we presumed that addition of anti-inflammatory agent into the surfactant may alleviate inflammation and enhance efficiency of the therapy, this study was performed to evaluate effects of surfactant therapy enriched with budesonide versus surfactant-only therapy on markers of oxidative stress in experimental model of MAS. Meconium suspension (25 mg/ml, 4 ml/kg) was instilled into the trachea of young rabbits, whereas one group of animals received saline instead of meconium (C group, n = 6). In meconium-instilled animals, respiratory failure developed within 30 min. Then, meconium-instilled animals were divided into 3 groups according to therapy (n = 6 each): with surfactant therapy (M + S group), with surfactant + budesonide therapy (M + S + B), and without therapy (M group). Surfactant therapy consisted of two bronchoalveolar lavages (BAL) with diluted surfactant (Curosurf, 5 mg phospholipids/ml, 10 ml/kg) followed by undiluted surfactant (100 mg phospholipids/kg), which was in M + S + B group enriched with budesonide (Pulmicort, 0.5 mg/ml). Animals were oxygen-ventilated for additional 5 hours. At the end of experiment, blood sample was taken for differential white blood cell (WBC) count. After euthanizing animals, left lung was saline-lavaged and cell differential in BAL was determined. Oxidative damage, i.e. oxidation of lipids (thiobarbituric acid reactive substance (TBARS) and conjugated dienes) and proteins (dityrosine and lysine-lipoperoxidation products) was estimated in lung homogenate and isolated mitochondria. Total antioxidant capacity was evaluated in lung homogenate and plasma. Meconium instillation increased transmigration of neutrophils and production of free radicals compared to controls (P < 0.05). Surfactant therapy, but particularly combined surfactant + budesonide therapy reduced markers of oxidative stress versus untreated animals (P < 0.05). In conclusion, budesonide added into surfactant enhanced effect of therapy on oxidative damage of the lung.
胎粪吸入综合征（MAS）是一种严重病症，可通过外源性表面活性剂和机械通气进行治疗。然而，胎粪引起的炎症、肺水肿和氧化损伤可能会使所递送的表面活性剂失活，从而降低治疗效果。由于我们推测在表面活性剂中添加抗炎剂可能会减轻炎症并提高治疗效率，因此进行了本研究，以评估在MAS实验模型中，富含布地奈德的表面活性剂治疗与单纯表面活性剂治疗对氧化应激标志物的影响。将胎粪悬液（25mg/ml，4ml/kg）滴入幼兔气管，而一组动物接受生理盐水而非胎粪（C组，n = 6）。在滴入胎粪的动物中，30分钟内出现呼吸衰竭。然后，根据治疗方法将滴入胎粪的动物分为3组（每组n = 6）：接受表面活性剂治疗（M + S组）、接受表面活性剂 + 布地奈德治疗（M + S + B组）和不接受治疗（M组）。表面活性剂治疗包括两次用稀释表面活性剂（珂立苏，5mg磷脂/ml，10ml/kg）进行的支气管肺泡灌洗（BAL），随后给予未稀释的表面活性剂（100mg磷脂/kg），在M + S + B组中表面活性剂富含布地奈德（普米克，0.5mg/ml）。动物再进行5小时的氧通气。实验结束时，采集血样进行白细胞分类计数。对动物实施安乐死后，用生理盐水冲洗左肺并测定BAL中的细胞分类。在肺匀浆和分离的线粒体中评估氧化损伤，即脂质氧化（硫代巴比妥酸反应性物质（TBARS）和共轭二烯）和蛋白质氧化（二酪氨酸和赖氨酸 - 脂质过氧化产物）。在肺匀浆和血浆中评估总抗氧化能力。与对照组相比，滴入胎粪增加了中性粒细胞的迁移和自由基的产生（P < 0.05）。与未治疗的动物相比，表面活性剂治疗，尤其是联合表面活性剂 + 布地奈德治疗降低了氧化应激标志物（P < 0.05）。总之，添加到表面活性剂中的布地奈德增强了治疗对肺氧化损伤的效果。
