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生长抑素可降低脂多糖诱导的内毒素血症大鼠模型中肿瘤坏死因子α的水平。

Somatostatin reduces the levels of tumor necrosis factor alpha in a rat model of endotoxemia induced by lipopolysaccharide.

作者信息

Landa J I, Alvarez Sánchez J, Grau M, Sánchez J A, Balibrea J L

机构信息

Research Center, Hospital Universitario 12 de Octubre, Madrid, Spain.

出版信息

Res Exp Med (Berl). 1995;195(5):317-25. doi: 10.1007/BF02576802.

DOI:10.1007/BF02576802
PMID:8579640
Abstract

The role of tumor necrosis factor alpha (TNF) in the toxic and lethal effects of the endotoxemia associated with septic shock is well known. This study was designed to establish whether natural somatostatin (SS-14) is capable of modifying the production of TNF in a model of septic shock induced in the rat by bacterial lipopolysaccharide (LPS), and its theoretical relationship to prostaglandin E2 (PGE2). An experimental study was carried out in 80 Wistar rats subjected to intravenous LPS injection. Perfusion of SS-14 at 2 micrograms/h or continuous isotonic saline (IS) at 0.1 ml/h started 30 min prior to LPS injection and continued until 90 min after. All the animals were primed 15 days earlier with on intraperitoneal dose of BCG (2.2 x 10(7) CFU). ELISA assays were used to measure TNF levels after 90 min of perfusion and those of PGE2 at 30 and 90 min. The effects of two different doses of LPS (0.5 mg/kg of body weight and 5 mg/kg bw) were compared. SS-14 administration was associated with a decrease in TNF levels (1130.0 +/- 272.4 vs 4720.0 +/- 1278.1 pg/ml, P = 0.013), and an increase in serum PGE2 basally (255.7 +/- 94.2 vs 62.0 +/- 10.6 pg/ml, P = 0.04) and after 90 min of perfusion (1872.7 +/- 1250.6 vs 1009.7 +/- 612.0 pg/ml, P = NS), there being a statistically significant correlation between the basal PGE2 levels and these TNF after 90 min when compared using a regression model (r = -0.88, P = 0.04 for the 0.5 mg/kg dose; r = -0.47, P = 0.07 for 5 mg/kg). At 90 min, the level of TNF also depended on the PGE2 values (r = 0.84, P = 0.07 for 0.5 mg/kg; r = 0.55, P = 0.03 for 5 mg/kg). Multiple regression permitted TNF levels to be estimated on the basis of basal and 90 min PGE2 levels (P = 0.03). Pretreatment with SS-14 led to a significant reduction of TNF and an increase of PGE2, there being an apparent correlation between the two.

摘要

肿瘤坏死因子α(TNF)在与感染性休克相关的内毒素血症的毒性和致死效应中的作用已广为人知。本研究旨在确定天然生长抑素(SS - 14)是否能够在细菌脂多糖(LPS)诱导的大鼠感染性休克模型中改变TNF的产生,以及其与前列腺素E2(PGE2)的理论关系。对80只接受静脉注射LPS的Wistar大鼠进行了一项实验研究。在注射LPS前30分钟开始以2微克/小时的速度灌注SS - 14或0.1毫升/小时的等渗盐水(IS),并持续至注射后90分钟。所有动物在15天前腹腔注射一剂卡介苗(2.2×10⁷CFU)进行预处理。采用ELISA法在灌注90分钟后测量TNF水平,在30分钟和90分钟时测量PGE2水平。比较了两种不同剂量LPS(0.5毫克/千克体重和5毫克/千克体重)的作用。给予SS - 14后TNF水平降低(1130.0±272.4对4720.0±1278.1皮克/毫升,P = 0.013),基础血清PGE2水平升高(255.7±94.2对62.0±10.6皮克/毫升,P = 0.04),灌注90分钟后也升高(1872.7±1250.6对1009.7±612.0皮克/毫升,P =无显著性差异),当使用回归模型比较时,基础PGE2水平与90分钟后的这些TNF水平之间存在统计学显著相关性(0.5毫克/千克剂量时r = -0.88,P = 0.04;5毫克/千克时r = -0.47,P = 0.07)。在90分钟时,TNF水平也取决于PGE2值(0.5毫克/千克时r = 0.84,P = 0.07;5毫克/千克时r = 0.55,P = 0.03)。多元回归允许根据基础和90分钟时的PGE2水平估计TNF水平(P = 0.03)。用SS - 14预处理导致TNF显著降低和PGE2升高,两者之间存在明显相关性。

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