de Oca J, Cuadrado S, Vallet J, Benasco C, Martín E, Ardanuy C, Closa D, Hotter G, Jaurrieta E
Department of Surgery, C.S.U.B. Hospital Prínceps d'Espanya, University of Barcelona, Spain.
J Surg Res. 1998 Feb 15;75(1):18-23. doi: 10.1006/jsre.1997.5244.
Experimental studies have shown that 21-aminosteroids (21-A) are powerful inhibitors of superoxide-mediated iron-dependent lipid peroxidation. This study was aimed at determining how far the blocking effect of one of these substances (lazaroid U74389G) on lipid peroxidation protects intestinal grafts morphologically and biologically in a heterotopic transplant model (SBT) in rats.
Heterotopic LEW were performed using Ringer lactate (4 degrees C) as preservation solution. In Group 1 (n = 7) the donor and recipient animals received 3 and 6 mg/kg of the 21-A U74389G, respectively. Group 2 (n = 7) received the same doses of the vehicle of the drug. Sham group underwent only a laparotomy. Bacterial translocation (BT) was determined in mesenteric lymph nodes (MLN), liver (L), and spleen (S) 60 min after reperfusion. Tissue myeloperoxidase (MPO), malondialdehyde (MDA), and percentage conversion xanthine dehydrogenase/xanthine oxidase (XD/XO) were also determined in the ileal graft. Histological damage was graded according to Park's classification.
Tissue MDA (nmol/mg prot) was significantly lower in Group 1 (0.53 +/- 0.09) than in Group 2 (3.66 +/- 1, P < 0.05) and showed levels similar to those of the sham-operated group (0.40 +/- 0.05). Injury grades were also significantly different in both study groups (Group 1, 0-1; Group 2, 2-3, P < 0.05). BT (log CFU/g tissue) in Group 1 were MLN, 0; L, 0.36; and S, 0. In Group 2, MLN, 1.07; L, 0.81; and S, 1.49 (P < 0.05 in MLN). Increase in MPO activity (U/g prot) in comparison with sham-operated animals was similar in the two study groups (Group 1, 1.49 +/- 0.58; Group 2, 1.22 +/- 0.46; Sham, 0.34 +/- 0.37 (P < 0.05 1,2 vs sham). Conversion of XD to XO was unaffected by the supplementation of the drug.
21A U74389G inhibits lipid peroxidation, protects intestinal graft, and reduces BT after heterotopic SBT in rats.
实验研究表明，21-氨基类固醇（21-A）是超氧化物介导的铁依赖性脂质过氧化的强力抑制剂。本研究旨在确定这些物质之一（拉扎罗类药物U74389G）对脂质过氧化的阻断作用在大鼠异位移植模型（SBT）中对肠道移植物的形态和生物学保护作用能达到何种程度。
使用乳酸林格液（4℃）作为保存液进行异位LEW移植。第1组（n = 7）供体和受体动物分别接受3和6 mg/kg的21-A U74389G。第2组（n = 7）接受相同剂量的药物载体。假手术组仅进行剖腹手术。再灌注60分钟后，测定肠系膜淋巴结（MLN）、肝脏（L）和脾脏（S）中的细菌移位（BT）。还测定了回肠移植物中的组织髓过氧化物酶（MPO）、丙二醛（MDA）以及黄嘌呤脱氢酶/黄嘌呤氧化酶（XD/XO）的转化率。根据帕克分类法对组织学损伤进行分级。
第1组的组织MDA（nmol/mg蛋白）（0.53±0.09）显著低于第2组（3.66±1，P<0.05），且与假手术组（0.40±0.05）的水平相似。两个研究组的损伤分级也有显著差异（第1组，0 - 1级；第2组，2 - 3级，P<0.05）。第1组的BT（log CFU/g组织）在MLN中为0；在L中为0.36；在S中为0。在第2组中，MLN为1.07；L为0.81；S为1.49（MLN中P<0.05）。与假手术动物相比，两个研究组的MPO活性（U/g蛋白）增加相似（第1组，1.49±0.58；第2组，1.22±0.46；假手术组，0.34±0.37（第1、2组与假手术组相比P<0.05）。XD向XO的转化不受药物补充的影响。
21A U74389G可抑制脂质过氧化，保护肠道移植物，并减少大鼠异位SBT后的BT。
