用21-氨基类固醇U-74389G治疗对大鼠实验性内毒素血症中肿瘤坏死因子-α释放的抑制作用。

Inhibition of tumor necrosis factor-alpha release in rat experimental endotoxemia by treatment with the 21-aminosteroid U-74389G.

作者信息

Lehmann C, Egerer K, Georgiew A, Weber M, Grune T, Kox W J

机构信息

Department of Anaesthesiology and Intensive Care, University Hospital Charité, Humboldt University, Berlin, Germany.

出版信息

Crit Care Med. 1999 Jun;27(6):1164-7. doi: 10.1097/00003246-199906000-00044.

DOI:10.1097/00003246-199906000-00044

PMID:10397223

Abstract

OBJECTIVE

To determine the effect of the 21-aminosteroid U-74389G on tumor necrosis factor (TNF)-alpha release in experimental endotoxemia.

DESIGN

Prospective, randomized, controlled animal study.

SETTING

Experimental laboratory.

SUBJECTS

Twenty-one male Wistar rats weighing 190+/-40 g.

INTERVENTIONS

The rats were divided equally into 3 groups: a) control; b) endotoxemia (5 mg/kg lipopolysaccharide [LPS] from Escherichia coli 055:B5); and c) endotoxemia and U-74389G administration 30 mins before (3 mg/kg) and 60 mins after (1.5 mg/kg) endotoxin challenge.

MEASUREMENTS AND MAIN RESULTS

At 0, 120, and 240 mins, serum levels of TNF-alpha were measured using a specific rat TNF-alpha ELISA kit. U-74389G-treated endotoxemic animals showed significantly reduced TNF-alpha release 120 mins after endotoxin challenge (control, 2.5+/-2.1 pg/mL; LPS, 4041+/-871 pg/mL; U-74389G, 1627+/-474 pg/mL [p < .05]). Two hundred forty minutes after LPS administration, TNF-alpha levels decreased, whereas values in the untreated LPS group remained twice as high as those in the U-74389G group (LPS, 863+/-182 pg/mL; U-74389G, 369+/-54 pg/mL [p < .05]).

CONCLUSIONS

The study demonstrated that administration of U-74389G, which has radical-scavenging and membrane-stabilizing properties, decreased TNF-alpha release during endotoxemia. Thus, 21-aminosteroids may lend themselves to evaluation in the treatment of septic states.

摘要

目的

确定21-氨基类固醇U-74389G对实验性内毒素血症中肿瘤坏死因子（TNF）-α释放的影响。

设计

前瞻性、随机、对照动物研究。

地点

实验实验室。

对象

21只体重190±40 g的雄性Wistar大鼠。

干预措施

将大鼠平均分为3组：a）对照组；b）内毒素血症组（5 mg/kg来自大肠杆菌055:B5的脂多糖[LPS]）；c）内毒素血症组，在内毒素攻击前30分钟（3 mg/kg）和攻击后60分钟（1.5 mg/kg）给予U-74389G。

测量指标及主要结果

在0、120和240分钟时，使用特异性大鼠TNF-α ELISA试剂盒测量血清TNF-α水平。接受U-74389G治疗的内毒素血症动物在内毒素攻击后120分钟时TNF-α释放显著减少（对照组，2.5±2.1 pg/mL；LPS组，4041±871 pg/mL；U-74389G组，1627±474 pg/mL [p <.05]）。LPS给药240分钟后，TNF-α水平下降，而未治疗的LPS组的值仍比U-74389G组高两倍（LPS组，863±182 pg/mL；U-74389G组，369±54 pg/mL [p <.05]）。