Manganese superoxide dismutase-plasmid/liposome (MnSOD-PL) administration protects mice from esophagitis associated with fractionated radiation
Manganese superoxide dismutase-plasmid/liposome (MnSOD-PL) administration protects mice from esophagitis associated with fractionated radiation
复制标题
施用超氧化物歧化酶锰质粒/脂质体（MnSOD-PL）可保护小鼠免受分段辐射引起的食管炎的影响
DOI：
10.1002/ijc.1023
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发表时间：
2001-08-20
影响因子：
6.4
通讯作者：
Greenberger, JS
中科院分区：
文献类型：
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作者：
Epperly, MW;Kagan, VE;Greenberger, JS
在单次辐射前食管内给予锰超氧化物歧化酶-质粒/脂质体（MnSOD-PL）已显示出保护小鼠免于致死性食管炎。在我们的研究中，C3 H/HeNsd小鼠以两种方案接受分次辐射：（i）在第一和第三分次之前24小时，每天18戈伊，持续4天，并施用MnSOD-PL，或（ii）在第一、第三和第五分次之前24小时，每天12戈伊，持续6天，并施用MnSOD-PL。对照辐射小鼠仅接受无脂质体或按照相同的时间表接受LacZ（细菌β-半乳糖苷酶基因）-质粒/脂质体（LacZ-PL）。我们测量了整个食管中的巯基耗竭和脂质过氧化（LP），并测试了一种新的质粒，血凝素（RA）表位标记的MnSOD（HA/MnSOD）的有效性。在分级方案中，接受MnSOD-PL而不是LacZ-PL（200 μ l质粒/脂质体，含有200 μ g质粒DNA）的小鼠显示出发病率显著降低、体重减轻减少和存活率提高。在37戈伊单次照射后4天和7天，食管表现出过氧化脂质显著增加，总体抗氧化剂水平降低，巯基减少，谷胱甘肽（GSH）减少。这些减少是由MnSOD-PL管理调制。HA-MnSOD质粒产物在给药后24小时在食管上皮的基底层中检测到，并且与谷胱甘肽过氧化物酶-质粒/脂质体（GPX-PL）或含有MnSOD蛋白、维生素E、辅酶Q10或21-氨基类固醇的脂质体相比，提供了显著的辐射保护。因此，MnSOD-PL管理显着提高耐受分次辐射和调制的GSH和脂质过氧化（LP）水平的辐射效应。这些研究为MnSOD-PL治疗转化为人类食管辐射保护提供了进一步的支持。(C)2001 Wiley-Liss，Inc.
Intraesophageal administration of manganese superoxide dismutase-plasmid/liposome (MnSOD-PL) prior to single fraction radiation has been shown to protect mice from lethal esophagitis. In our study, C3H/HeNsd mice received fractionated radiation in two protocols: (i) 18 Gy daily for four days with MnSOD-PL administration 24 hr prior to the first and third fraction, or (ii) 12 Gy daily for six days with MnSOD-PL 24 hr prior to the first, third, and fifth fraction. Control radiated mice received either no liposomes only or LacZ (bacterial beta -galactosidase gene)-plasmid/liposome (LacZ-PL) by the same schedules. We measured thiol depletion and lipid peroxidation (LP) in whole esophagus and tested the effectiveness of a new plasmid, hemagglutinin (RA) epitope-tagged MnSOD (HA/MnSOD). In fractionation protocols, mice receiving MnSOD-PL, but not LacZ-PL (200 mul of plasmid/liposomes containing 200 mug of plasmid DNA), showed a significant reduction in morbidity, decreased weight loss, and improved survival. Four and seven days after 37 Gy single fraction radiation, the esophagus demonstrated a significant increase in peroxidized lipids and reduction in overall antioxidant levels, reduced thiols, and decreased glutathione (GSH). These reductions were modulated by MnSOD-PL administration. The HA-MnSOD plasmid product was detected in the basal layers of the esophageal epithelium 24 hr after administration and provided significant radiation protection compared to glutathione peroxidase-plasmid/liposome (GPX-PL), or liposomes containing MnSOD protein, vitamin E, co-enzyme Q10, or 21-aminosteroid. Thus, MnSOD-PL administration significantly improved tolerance to fractionated radiation and modulated radiation effects on levels of GSH and lipid peroxidation (LP). These studies provide further support for translation of MnSOD-PL treatment into human esophageal radiation protection. (C) 2001 Wiley-Liss, Inc.