Herminghaus Anna, Eberhardt Rebecca, Truse Richard, Schulz Jan, Bauer Inge, Picker Olaf, Vollmer Christian
Department of Anaesthesiology, University of Düsseldorf, Düsseldorf, Germany.
Front Med (Lausanne). 2018 Oct 16;5:291. doi: 10.3389/fmed.2018.00291. eCollection 2018.
Locally applied nitroglycerin [nitric oxide (NO) donor] and iloprost (analog of prostacyclin PGI) improve regional gastric oxygenation and nitroglycerin preserves gastric mucosal barrier integrity. This suggests direct effects of these substances on oxygenation and barrier function. The aim of this study was to analyze the effect of iloprost and nitroglycerin on intestinal mitochondrial function and on mucosal barrier function . Mitochondrial oxygen consumption (respirometry) was determined in colon homogenates from 16 healthy rats before (baseline) and 15 min after incubation with nitroglycerin (25 and 250 μg/ml) and iloprost (0.1 and 1 μg/ml). State 2 (substrate-dependent oxygen consumption) and state 3 respiration (ADP-dependent oxygen consumption) were assessed and ADP/O ratio (ADP added/oxygen consumed) for complex I and II were calculated. For permeability measurement we used the Caco-2 monolayer. Fluorescein sulfonic acid (FS) (200 μg/ml) and the drugs were administered into the apical compartment of the transwell chamber. After 48 h, FS translocation was assessed as basolateral/apical FS. Both concentrations of nitroglycerin and iloprost reduced state 3 by stimulation via both complexes. Iloprost increased ADP/O ratio after stimulation via both complexes at both concentrations. Nitroglycerin increased ADP/O ratio at the higher concentration (250 μg/ml) after stimulation via complex I and at the lower concentration (25 μg/ml) via complex II. Neither nitroglycerin nor iloprost influenced FS translocation. Iloprost and nitroglycerin reduce the maximal mitochondrial respiration and improve the efficacy of oxidative phosphorylation in colon homogenates. Both drugs have no direct influence on mucosal barrier integrity of Caco-2 monolayers.
局部应用硝酸甘油（一氧化氮供体）和伊洛前列素（前列环素PGI类似物）可改善局部胃氧合，且硝酸甘油可维持胃黏膜屏障的完整性。这表明这些物质对氧合和屏障功能有直接作用。本研究旨在分析伊洛前列素和硝酸甘油对肠道线粒体功能及黏膜屏障功能的影响。在16只健康大鼠的结肠匀浆中，于孵育硝酸甘油（25和250μg/ml）及伊洛前列素（0.1和1μg/ml）前（基线）和孵育15分钟后，测定线粒体氧消耗（呼吸测定法）。评估状态2（底物依赖性氧消耗）和状态3呼吸（ADP依赖性氧消耗），并计算复合物I和II的ADP/O比值（添加的ADP/消耗的氧）。对于通透性测量，我们使用了Caco-2单层。将荧光素磺酸（FS）（200μg/ml）和药物加入Transwell小室的顶侧隔室。48小时后，评估FS转运情况，以基底外侧/顶侧FS表示。两种浓度的硝酸甘油和伊洛前列素均通过两种复合物刺激降低状态3。两种浓度的伊洛前列素在通过两种复合物刺激后均提高了ADP/O比值。硝酸甘油在较高浓度（250μg/ml）通过复合物I刺激后及较低浓度（25μg/ml）通过复合物II刺激后提高了ADP/O比值。硝酸甘油和伊洛前列素均未影响FS转运。伊洛前列素和硝酸甘油可降低结肠匀浆中线粒体的最大呼吸，并提高氧化磷酸化的效率。两种药物对Caco-2单层的黏膜屏障完整性均无直接影响。
