Heat Shock Preconditioning Reduces the Formation of 8-hydroxy-2′-deoxyguanosine and 4-hydroxy-2-nonenal Modified Proteins in Ischemia-reperfused Liver of Rats
Heat Shock Preconditioning Reduces the Formation of 8-hydroxy-2′-deoxyguanosine and 4-hydroxy-2-nonenal Modified Proteins in Ischemia-reperfused Liver of Rats
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DOI：
10.1080/10715760290006385
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发表时间：
2002-01
影响因子：
3.3
通讯作者：
K. Yamagami;Yuzo Yamamoto;S. Toyokuni;K. Hata;Y. Yamaoka
中科院分区：
文献类型：
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作者：
K. Yamagami;Yuzo Yamamoto;S. Toyokuni;K. Hata;Y. Yamaoka
热休克预处理（HSPC）是一种很有前途的提供缺血耐受的策略。本研究的目的是研究HSPC在防止肝脏缺血再灌注过程中细胞蛋白质和DNA氧化损伤的有效性。雄性Wistar大鼠分为热休克组（HS组）和对照组（C组）。HS组于缺血前48 h给予HSPC，42 ℃，15 μ min，所有大鼠均行肝脏热缺血30 μ min，再灌注。比较各组大鼠肝组织中8-羟基-2 '-脱氧鸟苷（8-OHdG）、4-羟基-2-壬烯醛（HNE）修饰蛋白的形成、动物存活率以及生化和组织学指标的变化。热休克蛋白72仅在HS组产生。HS组大鼠7 d存活率（10/10）明显高于C组（5/10）（P <0.01）。再灌注40 μ min时，HS组血清丙氨酸氨基转移酶（n = 10，p <0.01）和肝组织三磷酸腺苷（n =10，p <0.01）的释放明显优于C组。高效液相色谱法测定肝组织中8-OHdG的生成，HS组明显抑制（p <0.01）。HNE修饰的蛋白质的产生，通过Western印迹分析确定也减少组HS。这些结果也得到了免疫组化分析的证实。如通过肝脏缺血-再灌注期间产生的8-OHdG和HNE修饰的蛋白质的水平所确定的，HSPC减少了肝组织中细胞蛋白质和DNA的氧化损伤。
Heat shock preconditioning (HSPC) is a promising strategy for providing ischemic tolerance. The objective of this study is to investigate the effectiveness of HSPC in preventing oxidative damage of cellular proteins and DNA during ischemia-reperfusion of the liver. Male Wistar rats were divided into a heat shock group (group HS) and control (group C). Forty-eight hours prior to ischemia, rats in group HS received HSPC at 42°C for 15 u min. All rats received hepatic warm ischemia for 30 u min and subsequent reperfusion. The formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG), 4-hydroxy-2-nonenal (HNE) modified proteins in liver tissue, survival rate of the animals, and changes in biochemical and histological parameters were compared between groups. Heat shock protein 72 was produced only in group HS. The 7-day survival of rats was significantly better in group HS (10/10) than in group C (5/10) ( p <0.01). The serum release of alanine aminotransferase ( n =10, p <0.01) and the concentration of adenosine triphosphate in liver tissue ( n =10, p <0.01) 40 u min after reperfusion was significantly better in group HS than in group C. The formation of 8-OHdG in liver tissue measured by high-performance liquid chromatography was suppressed in group HS ( p <0.01). The production of HNE-modified proteins as determined by Western-blot analysis was also decreased in group HS. These results were also confirmed by immunohistochemical analysis. As determined by levels of 8-OHdG and HNE-modified proteins produced during ischemia-reperfusion of the liver, HSPC reduced the oxidative injury of cellular proteins and DNA in the liver tissue.