P38抑制剂SB203580对小鼠辐射致死效应和小肠损伤的保护作用  

The protective effects of SB203580 against mortality and radiation induced intestinal injury of mice

作　　者：常建辉 张恒 关方霞[2] 王月英 李德冠 吴红英 王成春[2] 周长辉[2] 翟志斌 路璐 王小春 侯琦[3] 孟爱民 

机构地区：[1]中国医学科学院、北京协和医学院放射医学研究所,天津市分子核医学重点实验室,天津300192 [2]郑州大学生物工程系,河南郑州450051 [3]中国医学科学院、北京协和医学院药物研究所,北京100050

出　　处：《药学学报》2011年第4期395-399,共5页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(30770645,30828011,81072237);天津市自然科学基金资助项目(08JCYBJC07300);国家重点基础研究发展计划(973计划)重大专项(2011CB964800-G)

摘　　要：本研究主要观察p38抑制剂SB203580对小鼠辐射致死效应和小肠损伤的保护作用。在小鼠辐射致死效应实验中,随机分为对照组、照射组和照射给药组。对照组给予假照射,其他两组接受7.2Gy照射,照射给药组在照射前0.5 h腹腔注射给药,以后隔天给药(共5次),观察小鼠30天生存率。小肠损伤保护实验中分组和照射剂量相同。24 h后处死小鼠并取小肠组织进行HE及免疫组化染色。结果显示,照射给药组小鼠30天生存率比照射组提高40%。与照射组相比,照射给药组的小肠隐窝细胞p-p38、p53表达下降,凋亡细胞数量下降,Ki67表达升高,差异均有统计学意义(P<0.01)。结果表明,SB203580特异性抑制全身照射小鼠小肠隐窝细胞p38激活及p53表达升高,小肠隐窝细胞凋亡减少,增殖能力提高,30天小鼠生存率提高。提示SB203580对小鼠辐射致死效应和小肠损伤有一定保护作用,p38通路在辐射致死效应和辐射诱导小肠上皮细胞损伤中起着一定的作用。This study is to investigate the protective effects of the SB203580 against radiation induced mortality and intestinal injury of mice.A total of 67 male C57BL/6 mice（20.0-22.0 g） were matched according to body weight and randomly assigned to one of three groups： control,total body irradiation exposure（IR,7.2Gy） only,and IR（7.2Gy） ＋ SB203580（15 mg-kg-1）.30 days survival rate was observed in the experiment.In intestinal injury experiment,the expression levels of caspase-3,Ki67,p53 and p-p38 were assayed in the mice intestine crypts.The results showed that the 30 days survival rate was 100%（control）,0（IR） and 40%（IR ＋ SB203580）,separately.Compared to the IR groups,the positive cells of caspase-3,p53 and p-p38 in crypt cells decreased 33.00%,21.78% and 34.63%,respectively.The rate of positive cells of Ki67 increased 37.96%.Significant difference was found between all of them（P0.01）.SB203580 potently protected against radiation-induced lethal and intestinal injury in mice,and it may be a potential radio protector.

关 键 词：SB203580 辐射损伤 生存率 细胞凋亡 P38通路 

分 类 号：R965[医药卫生—药理学]