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拉扎罗类化合物U74389G可改善大鼠肺移植模型中的缺血再灌注损伤。

Lazaroid U74389G ameliorates ischemia-reperfusion injury in the rat lung transplant model.

作者信息

Kuwaki K, Komatsu K, Sohma H, Abe T

机构信息

Department of Thoracic and Cardiovascular Surgery, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo 060-8556.

出版信息

Ann Thorac Cardiovasc Surg. 1999 Feb;5(1):11-7.

Abstract

We investigated the effect of Lazaroid U74389G on ischemia-reperfusion injury in the rat orthotopic left lung transplantation model. Five groups of reperfused lungs were studied. In group I, donor lungs were transplanted after 12 hours of preservation in University of Wisconsin (UW) solution at 4C. In groups II, III, and IV, Lazaroid was intravenously administrated at a dose of 1 mg/kg, 8 mg/kg, and 15 mg/kg, respectively, to the donors 30 minutes before preservation and also to the recipients 30 minutes before reperfusion after 12 hours of storage in UW solution at 4C. In group V, Lazaroid was added to the UW solution (80 micromol/l), and also was administered intravenously (6 mg/kg) 30 minutes before reperfusion. After 1 hour of reperfusion, gas exchange function and tissue lipid peroxide levels were significantly improved in Lazaroid-treated groups III, and V compared with no treatment group I. Histologic damage was less severe in groups III, IV, and V than in group I. These findings suggest that Lazaroid U74389G ameliorates ischemia-reperfusion injury in the rat lung transplants by inhibiting lipid peroxidation, regardless of whether it is administrated intravenously or given as an additive to the preservation solution.

摘要

我们在大鼠原位左肺移植模型中研究了拉扎罗类药物U74389G对缺血再灌注损伤的影响。研究了五组再灌注肺。在第一组中,供体肺在4℃的威斯康星大学(UW)溶液中保存12小时后进行移植。在第二、三、四组中,分别在保存前30分钟给供体静脉注射剂量为1mg/kg、8mg/kg和15mg/kg的拉扎罗类药物,并且在4℃的UW溶液中保存12小时后再灌注前30分钟给受体也静脉注射该药物。在第五组中,将拉扎罗类药物添加到UW溶液中(80微摩尔/升),并且在再灌注前30分钟也静脉注射(6mg/kg)。再灌注1小时后,与未治疗的第一组相比,拉扎罗类药物治疗的第三组和第五组的气体交换功能和组织脂质过氧化物水平显著改善。第三、四、五组的组织学损伤比第一组轻。这些发现表明,拉扎罗类药物U74389G通过抑制脂质过氧化减轻大鼠肺移植中的缺血再灌注损伤,无论它是静脉给药还是作为保存液添加剂给药。

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