Epperly Michael W, Tyurina Yulia Y, Nie Suhua, Niu Yun Yun, Zhang Xichen, Kagan Valerian, Greenberger Joel S
Department of Radiation Oncology, University of Pittsburgh Cancer Institute and School of Environmental Health, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
In Vivo. 2005 Nov-Dec;19(6):997-1004.
Ionizing irradiation-induced cellular and tissue damage is mediated in part by resultant radiochemical reactions and resultant oxidative stress. Irradiation-induced reactive oxygen and nitrogen species include: superoxide, nitric oxide, hydroxyl radical and hydrogen peroxide. The biochemical combination of superoxide and nitric oxide radicals forms peroxynitrite, a potent oxidant known to induce lipid peroxidation.
The antioxidant capacity and lipid peroxidation of the esophagus were determined following irradiation.
In the present studies, measurements of total antioxidant capacity did not change in the esophagus of control irradiated or control plasmid pNGVL3-PL intraesophageally-injected mice. In contrast, manganese superoxide dismutase-plasmid/liposome (MnSOD-PL) intraesophageally-treated mice showed a significant increase in antioxidant capacity persisting for seven days. Lipid peroxidative changes induced in the control irradiated mouse esophagus decreased over seven days after irradiation of C3H/HeNHsd mice exposed to 37 Gy in a single fraction. MnSOD-PL radioprotective gene therapy administered intraorally 24 hours prior to irradiation did not significantly reduce the kinetics of induction of total peroxidated lipids over the first seven days after irradiation but did decrease lipid peroxidation at days 14 and 21.
These studies demonstrate the antioxidant function of MnSOD-PL gene therapy to the esophagus, which is detectable as a reduction in irradiation-induced lipid peroxidation.
电离辐射诱导的细胞和组织损伤部分是由所产生的放射化学反应和由此产生的氧化应激介导的。辐射诱导的活性氧和氮物种包括：超氧化物、一氧化氮、羟基自由基和过氧化氢。超氧化物和一氧化氮自由基的生化结合形成过氧亚硝酸盐，这是一种已知可诱导脂质过氧化的强效氧化剂。
在照射后测定食管的抗氧化能力和脂质过氧化情况。
在本研究中，对照照射小鼠或经食管内注射对照质粒pNGVL3-PL的小鼠食管中总抗氧化能力的测量值没有变化。相比之下，经食管内治疗的锰超氧化物歧化酶-质粒/脂质体（MnSOD-PL）小鼠的抗氧化能力在7天内持续显著增加。在单次接受37 Gy照射的C3H/HeNHsd小鼠中，对照照射小鼠食管中诱导的脂质过氧化变化在照射后7天内有所下降。在照射前24小时经口给予MnSOD-PL放射保护基因治疗，在照射后的前7天内并没有显著降低总过氧化脂质的诱导动力学，但在第14天和第21天确实降低了脂质过氧化。
这些研究证明了MnSOD-PL基因治疗对食管的抗氧化功能，这可表现为辐射诱导的脂质过氧化减少。
