21-氨基类固醇U-74389G改善大鼠内脏缺血再灌注损伤后的生存率并逆转内皮功能障碍。

Improved survival and reversal of endothelial dysfunction by the 21-aminosteroid, U-74389G in splanchnic ischaemia-reperfusion injury in the rat.

作者信息

Squadrito F, Altavilla D, Ammendolia L, Squadrito G, Campo G M, Sperandeo A, Canale P, Ioculano M, Saitta A, Caputi A P

机构信息

Institute of Pharmacology, School of Medicine, University of Messina, Italy.

出版信息

Br J Pharmacol. 1995 Jun;115(3):395-400. doi: 10.1111/j.1476-5381.1995.tb16346.x.

DOI:10.1111/j.1476-5381.1995.tb16346.x

PMID:7582448

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1908426/

Abstract

Anaesthetized rats subjected to total occlusion of the superior mesenteric artery and the coeliac trunk for 45 min developed a severe shock state (splanchnic artery occlusion, SAO shock) resulting in death within 70-90 min after release of the occlusion. Sham-operated animals were used as controls. 2. Survival rate, survival time, serum tumour necrosis factor (TNF-alpha), white blood cell (WBC) count, mean arterial blood pressure (MAP), plasma malonyladehyde (MAL); myeloperoxidase activity (MPO) and the responsiveness to acetylcholine (ACh 10 nM-10 microM) of aortic rings were investigated. 3. SAO shocked rats had a decreased survival rate and survival time (74 +/- 10 min, while sham-shocked rats survived more than 4 h), reduced mean arterial blood pressure, increased serum levels of TNF-alpha (267 +/- 13 u ml-1) and plasma levels of MAL (57 +/- 7 nmol ml-1), enhanced MPO activity in the ileum (0.23 +/- 0.04 u x 10(-3) g-1 tissue) and in the lung (2.2 +/- 0.8 u x 10(-3) g-1 tissue), leukopenia and reduced responsiveness to ACh of aortic rings. 4. The 21-aminosteroid U-74389G (30 mg kg-1, i.v.) increased survival (survival time = 232 +/- 15 min), lowered the serum levels of TNF-alpha and the plasma levels of MAL, reduced leukopenia and MPO activity both in the ileum (0.021 +/- 0.004 u x 10(-3) g-1 tissue) and in the lung (0.23 +/- 0.03 u x 10(-3) g-1 tissue), improved MAP and restored the responsiveness to ACh of aortic rings. 5. Our data suggest that U-74389G is a potent lipid peroxidation inhibitor and that it has antishock and endothelial protective actions.

摘要

对麻醉大鼠进行肠系膜上动脉和腹腔干完全闭塞45分钟，会引发严重休克状态（内脏动脉闭塞，SAO休克），导致在闭塞解除后70 - 90分钟内死亡。假手术动物用作对照。2. 研究了存活率、存活时间、血清肿瘤坏死因子（TNF-α）、白细胞（WBC）计数、平均动脉血压（MAP）、血浆丙二醛（MAL）；髓过氧化物酶活性（MPO）以及主动脉环对乙酰胆碱（ACh 10 nM - 10 μM）的反应性。3. SAO休克大鼠的存活率和存活时间降低（74 ± 10分钟，而假休克大鼠存活超过4小时），平均动脉血压降低，血清TNF-α水平升高（267 ± 13 u/ml），血浆MAL水平升高（57 ± 7 nmol/ml），回肠（0.23 ± 0.04 u×10⁻³ g⁻¹组织）和肺（2.2 ± 0.8 u×10⁻³ g⁻¹组织）中的MPO活性增强，白细胞减少，主动脉环对ACh的反应性降低。4. 21 - 氨基类固醇U - 74389G（30 mg/kg，静脉注射）提高了存活率（存活时间 = 232 ± 15分钟），降低了血清TNF-α水平和血浆MAL水平，减少了白细胞减少以及回肠（0.021 ± 0.004 u×10⁻³ g⁻¹组织）和肺（0.23 ± 0.03 u×10⁻³ g⁻¹组织）中的MPO活性，改善了MAP并恢复了主动脉环对ACh的反应性。5. 我们的数据表明U - 74389G是一种有效的脂质过氧化抑制剂，并且具有抗休克和内皮保护作用。