The radiation protection role of heparin-SOD conjugate in irradiated mice

ABSTRACT Heparin-SOD conjugate (Hep-SOD) was prepared by modifying Cu,Zn-SOD with heparin. An acute radiation-induced mouse injury model was constructed to study the radiation protection effects of Hep-SOD conjugate. Fifty-six mice were randomly divided into seven groups: (I) normal control group; (II) irradiated control group; (III) positive control group (amifostine group, 300 mg/kg); (IV) SOD group (35000 U/kg); (V) high dosage of Hep-SOD group (70000 U/kg); (VI) medium dosage of Hep-SOD group (35000 U/kg); (VII) low dosage of Hep-SOD group (17500 U/kg). Drugs were intraperitoneally injected into each mouse 1 h before radiation except for the normal control group. All the irradiated groups were irradiated with 6 Gy. Organ indices, haematopoietic function indices, peripheral blood cells, liver function test, oxidative stress state and pathological observation were detected to study the effects of Hep-SOD on irradiated mice. Results showed that bone marrow suppression of irradiated mice could be reduced when treated by Hep-SOD before radiation. Oxidative stress detection and pathological observation of the liver and intestine showed that the damage caused by radiation was relieved when mice were treated with Hep-SOD before radiation. This study shows a new direction to prevent organisms from the damage caused by radiation.

摘要：本研究通过对铜锌超氧化物歧化酶（Cu,Zn-SOD）进行肝素修饰，制备得到肝素-超氧化物歧化酶偶联物（Heparin-SOD conjugate，简称Hep-SOD）。为探究该偶联物的辐射防护效应，本研究构建了急性辐射诱导小鼠损伤模型。将56只小鼠随机分为7组：(I) 正常对照组；(II) 照射对照组；(III) 阳性对照组（氨磷汀组，300 mg/kg）；(IV) 超氧化物歧化酶（SOD）组（35000 U/kg）；(V) 高剂量Hep-SOD组（70000 U/kg）；(VI) 中剂量Hep-SOD组（35000 U/kg）；(VII) 低剂量Hep-SOD组（17500 U/kg）。除正常对照组外，其余各组小鼠均于照射前1小时行腹腔注射给药。所有照射组均接受6 Gy剂量的辐射照射。本研究通过检测脏器指数、造血功能指标、外周血细胞、肝功能、氧化应激状态并开展病理学观察，探究Hep-SOD对受照小鼠的干预效果。结果表明，辐射前给予Hep-SOD处理可有效减轻受照小鼠的骨髓抑制症状；对肝脏与肠道的氧化应激检测及病理学观察结果显示，该偶联物可缓解辐射所致的组织损伤。本研究为预防生物体遭受辐射损伤提供了全新的研究方向。