Toll样受体2/6激动剂CBLB601脂肽的辐射防护作用  

Radioprotection effects of Toll-like receptors 2 /6 agonist CBLB601 lipopeptide

作　　者：洪剑[1,2] 王治东[1] 王磊[3] 张美江[1] 许望翔[1] 詹轶群[1] 葛常辉[1] 陈肖华[1] 杨晓明[1] 

机构地区：[1]军事医学科学院放射与辐射医学研究所,北京100850 [2]解放军第309医院放射科,北京100090 [3]天津大学化工学院,天津230032

出　　处：《国际药学研究杂志》2013年第5期620-624,共5页Journal of International Pharmaceutical Research

基　　金：国家"重大新药创制"科技重大专项资助项目(2010ZX09401)

摘　　要：目的研究CBLB601脂肽的辐射防护作用。方法 140只C57BL/6雄性小鼠随机分为照射对照组,氨磷汀150mg/kg组,CBLB601 0.015、0.05、0.15、0.5和0.75 mg/kg组,每组20只,分别于照前腹腔注射给药,接受8.0 Gy60Coγ射线照射后,观察受照小鼠30 d存活率和平均生存时间。另75只C57BL/6雄性小鼠随机分为照射对照组,氨磷汀150 mg/kg组,CBLB601 0.15、0.5和0.75 mg/kg组,每组15只,给药方式同前。接受6.5 Gy60Coγ射线照射后,检测照射前2 d和照后30 d内小鼠外周血细胞计数的变化;照射后第14天制备小鼠胸骨骨髓切片,观察骨髓组织病理学变化。结果与照射对照组相比,CBLB601 0.15、0.5和0.75 mg/kg给药组小鼠照射后30 d存活率显著提高(P<0.01),平均存活时间显著延长(P<0.01)。6.5 Gy60Coγ射线照射后,CBLB601各给药组小鼠外周血白细胞、红细胞、血红蛋白、血小板和中性粒细胞最低值均显著提高,外周血白细胞计数和中性粒细胞降低的持续时间也显著缩短;骨髓组织病理学检测结果表明,CBLB601能明显减轻辐射导致的髓系造血细胞减少、骨髓腔出血和水肿。结论 CBLB601对急性放射病小鼠有明显的辐射防护作用。Objective To detect the radioprotection activity of lipopeptide CBLB601. Methods A total of 140C57BL/6 male mice were randomly assigned to irradiation control, amifostine 150 mg/kg（ip） and CBLB601 0. 015, 0. 05, 0. 15, 0. 5 and 0. 75 mg/ kg（ip） groups （20 mice per group） before 8.0 Gy 6o Co γ-ray total body irradiation （TBI）, 30 d survival rate and average survival time were calculated. Another 75 male mice were assigned to irradiation control, amifostine 150 mg/kg（ip） and CBLB601 0. 15, 0. 5, 0. 75 mg/kg（ip） group（ 15 mice per group） at random before 6. 5 Gy 60Co CBLB601; Toll-like receptors; acute radiation injury; radioprotection effect-ray irradiation, the peripheral blood cell counts before and after irradiation were monitered. Histopathological changes of bone marrow in mice were evaluated at day 14 after irradiation. Resuits Compared with irradiation control group, the 30 d survival rate and average survival time of mice in CBLB601 treatment groups exposed to 8.0 Gy 6oCo -ray TBI （ P 〈 0.01 ） were significantly elevated. The counts of leukocytes, neutrophils , hemoglobin and platelet of the peripheral blood of mice in CBLB601 0. 15, 0. 5 and 0. 75 mg/kg groups were significantly increased exposed to 6. 5 Gy a）Co -t-ray（ P 〈 0. 01 ）, the nadirs of leukocytes, neutrophils, platelets and hemoglobin were elevated, and duration of pancytopenia was shortened. Histopathological assay revealed that CBLB601 can obviously attenuate myeloid derived hematopoietic cytopenia, hemorrbage and edema in marrow cavity after irradiation. Conclusion CBLB601 has obvious radioprotection effects on acute radiation in- jury of mice exposed to 6Co-γ-ray.

关 键 词：CBLB601 TOLL样受体 急性辐射损伤 辐射防护 

分 类 号：R142[医药卫生—公共卫生与预防医学]