Yu Yin-Hang, Ren Gui-Ping, Liu Yao-Nan, Qu Su-Su, Bai Fu-Liang, Zhang Tong, Wang Wen-Fei, Tian Gui-You, Ye Xian-Long, Li De-Shan
Yao Xue Xue Bao. 2014 Jul;49(7):1000-6.
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 x kg(-1) x 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 x kg(-1) x 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) x min(-1) x 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 x mg(-1) (protein), P < 0.01]. Comparing with the model group, the activities of SOD, GPx, CAT and T-AOC of the three different doses FGF-21 treatment groups were also improved in a dose-dependent manner. This study demonstrates that FGF-21 can ameliorate learning and memory abilities of D-galactose induced aging mice, improve the antioxidant abilities in brain tissue and delay brain aging. This finding provides a theoretical support for clinical application of FGF-21 as a novel therapeutics for preventing aging.
本研究旨在探讨成纤维细胞生长因子21(FGF-21)对D-半乳糖诱导的衰老小鼠学习记忆能力及抗氧化能力的影响。将体重(37.1±0.62)g的昆明小鼠随机分为正常对照组、模型组以及FGF-21高、中、低剂量组(n = 8)。每组小鼠颈部皮下注射180 mg·kg⁻¹·d⁻¹的D-半乳糖,每日1次,连续8周。同时,给予FGF-21处理的小鼠颈部皮下注射FGF-21,每日剂量分别为5、2和1 mg·kg⁻¹·d⁻¹。正常对照组小鼠颈部皮下注射生理盐水。实验第7周,通过水迷宫和跳台试验测定小鼠的学习记忆能力。实验结束时,处死小鼠,每组通过HE染色观察海马细胞损伤情况。测定小鼠脑内活性氧(ROS)、丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GPx)、过氧化氢酶(CAT)及总抗氧化能力(T-AOC)。结果显示,与模型组相比,不同剂量的FGF-21均可缩短水迷宫实验中到达终点的时间(P < 0.01或P < 0.05)以及触碰盲侧的次数(P < 0.01或P < 0.05)。在跳台试验中,FGF-21还可延长潜伏期(P < 0.05)并减少错误次数(P < 0.01或P < 0.05)。HE染色结果表明,FGF-21可显著减轻海马区脑细胞损伤。三种不同剂量FGF-21处理组的ROS和MDA水平均显著低于模型组[(5.58±1.07)、(7.78±1.92)、(9.03±1.77)对(12.75±2.02)pmol(DCF)·min⁻¹·mg⁻¹,P < 0.01或P < 0.05],[(2.92±0.71)、(4.21±0.81)、(4.41±0.97)对(5.62±0.63)nmol·mg⁻¹(蛋白),P < 0.01]。与模型组相比,三种不同剂量FGF-21处理组的SOD、GPx、CAT活性及T-AOC也呈剂量依赖性升高。本研究表明,FGF-21可改善D-半乳糖诱导的衰老小鼠的学习记忆能力,提高脑组织抗氧化能力,延缓脑衰老。这一发现为FGF-21作为预防衰老的新型治疗药物的临床应用提供了理论支持。