FGF-21对D-半乳糖诱导的衰老模型小鼠学习记忆能力和脑组织抗氧化能力的影响  

Effect of FGF-21 on learning and memory ability and antioxidant capacity in brain tissue of D-galactose-induced aging mice

作　　者：于引航[1] 任桂萍[1] 刘要南 曲素素[1] 白福良[1] 张童[1] 王文飞[1] 田贵游[1] 叶贤龙[1] 李德山[1] 

机构地区：[1]东北农业大学生命科学学院,黑龙江哈尔滨150030

出　　处：《药学学报》2014年第7期1000-1006,共7页Acta Pharmaceutica Sinica

基　　金：黑龙江省发改委项目(黑发改项目[2011]1570号);黑龙江省教育厅科学技术研究项目(12521z004);哈尔滨市科技创新人才研究专项资金项目(2012RFXXS034);黑龙江省高校科技成果产业化前期研发培育项目(1252CGZH29);黑龙江省博士后科研启动基金(LBH-Q09162);国家自然基金东北农业大学生物学理科基地科研训练及科研能力提高项目(J1210069/J0106)

摘　　要：本研究探讨成纤维细胞生长因子-21(FGF-21)对D-半乳糖致衰老小鼠脑组织学习记忆与抗氧化的影响。实验分为正常对照组、模型组及FGF-21高、中、低剂量处理组,模型组及FGF-21处理组,连续8周于小鼠背部皮下注射D-半乳糖180 mg·kg-1·d-1,FGF-21处理组同时给予颈部皮下注射FGF-21(5、2及1 mg·kg-1·d-1),正常对照组颈部皮下注射等量生理盐水。实验第7周时采用程控水迷宫和跳台仪检测各组小鼠的学习记忆能力。实验结束后取各组大脑对其海马区采用HE染色观察其海马区细胞损伤程度,并测定脑组织中活性氧(reactive oxygen species,ROS)、丙二醛(MDA)的含量,超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GPx)、过氧化氢酶(CAT)、总抗氧化能力(T-AOC)的活性。结果表明,与模型组相比,FGF-21能显著缩短D-半乳糖衰老小鼠在水迷宫中到达终点的时间(P<0.01,P<0.05)、降低碰撞盲端的次数(P<0.01,P<0.05)、延长小鼠跳台实验的潜伏期(P<0.05)及降低错误次数(P<0.01,P<0.05)。HE染色结果显示,FGF-21能明显降低大脑海马区细胞损伤情况。FGF-21能降低衰老模型小鼠脑组织ROS(P<0.01,P<0.05)和MDA(P<0.01,P<0.05)的含量,提高SOD、GPx、CAT和T-AOC的活性,且呈剂量依赖性。结果表明,FGF-21能够改善D-半乳糖衰老模型小鼠的学习记忆能力,提高脑组织的抗氧化能力,具有一定的延缓脑衰老的作用。This study aims to investigate the effects of fibroblast growth factor 21（FGF-21） on learning and memory abilities and antioxidant capacity of D-galactose-induced aging mice. Kunming mice（37.1 ± 0.62） g were randomly divided into normal control group, model group and FGF-21 high, medium and low dose groups（n = 8）. Each group was injected in cervical part subcutaneously with D-galactose 180 mg·kg-1·d-1 once a day for 8 weeks. At the same time, FGF-21-treated mice were administered with FGF-21 by giving subcutaneous injection in cervical part at the daily doses of 5, 2 and 1 mg·kg-1·d-1. The normal control group was given with normal saline by subcutaneous injection in cervical part. At seventh week of the experiment, the learning and memory abilities of mice were determined by water maze and jumping stand tests. At the end of the experiment, the mice were sacrificed and the cells damage of hippocampus was observed by HE staining in each group. Reactive oxygen species（ROS）, malondialdehyde（MDA）, superoxide dismutase（SOD）, glutathione peroxidase（GPx）, catalase（CAT） and total antioxidant capacity（T-AOC） in the brain of mice were determined. The results showed that different doses of FGF-21 could reduce the time reaching the end（P 0.01 or P 0.05） and the number of touching blind side（P 0.01 or P 0.05） in the water maze comparing with the model group. It could also prolong the latency time（P 0.05） and decrease the number of errors（P 0.01 or P 0.05） in the step down test. The result of HE staining showed that FGF-21 could significantly reduce brain cell damage in the hippocampus. The ROS and MDA levels of three different doses FGF-21 treatment group reduced significantly than that of the model group [（5.58 ± 1.07）,（7.78 ± 1.92）,（9.03 ± 1.77） vs（12.75 ± 2.02） pmol（DCF）·min-1·mg-1, P 0.01 or P 0.05], [（2.92 ± 0.71）,（4.21 ± 0.81）,（4.41 ± 0.97） vs（5.62 ± 0.63） nmol·mg-1（protein）, P 0.01]. Comparing with the model grou

关 键 词：成纤维细胞生长因子-21 衰老 抗氧化 学习记忆能力 半乳糖 

分 类 号：R965[医药卫生—药理学]