卫生研究

目的比较应用于衰老相关研究的D-半乳糖模型鼠与自然衰老鼠各种衰老指标的异同。方法采用昆明鼠作为受试动物,将动物分为3组:1.5月龄鼠给予D-半乳糖45天作为D-半乳糖模型组;15月龄鼠作为自然衰老组;3月龄鼠作为正常对照组。对3组动物分别进行了免疫(迟发型变态反应、半数溶血值的测定、抗体生成细胞检测和NK细胞活性测定)、生化[丙二醛(MDA)测定、超氧化物歧化酶(SOD)活力测定及SODmRNA的测定和SOD蛋白的测定]、行为(小鼠水迷宫试验和神经递质测定)、病理(常规病理和免疫组化蛋白测定)等多项指标的测定和分析。结果自然衰老组半数溶血值与正常对照组比较明显降低(P<0.05),而D-半乳糖模型组与对照组比较无明显差异。D-半乳糖模型组和自然衰老组SOD活性均低于对照组(P<0.01)、MDA含量均高于对照组(P<0.05,P<0.01),两组间无明显差异。行为学试验显示,自然衰老组与正常对照组相比不同测试阶段游泳时间延长,D-半乳糖衰老模型组与正常对照组相比无明显差异,自然衰老组脑组织肾上腺素(E)和组织多巴胺(DA)均降低(P<0.05,P<0.01),D-半乳糖模型组脑组织E和DA降低不明显,神经递质的改变与行为试验结果一致;自然衰老组和D-半乳糖模型SOD基因表达均低于正常对照组(P<0.05),其SODmRNA含量降低与SOD活性、SOD蛋白表达水平降低一致。结论D-半乳糖模型鼠虽然某些指标接近自然衰老鼠,但免疫、行为等方面与自然衰老鼠相比尚存在较大差异。D-半乳糖模型鼠是由化学损伤造成的,难以真实反映衰老的生理生化改变。因此D-半乳糖模型鼠可能不宜应用于免疫、行为等方面的衰老研究。

Objective To explore the feasibility of D-galactose treated mice's implication in aging related study by comparing the difference of all kinds of index between D-galactose treated mice and nomal aging mice. Methods Kunming mice were used as test animals, which were divided into three groups: D-galactose treated group, normal aging group and young mice group (as control group). Immunology index, including delayed-type hypersensitivity, half hemolysis concentration, plaque forming cell, NK cell activity, were detected. Biochemical index, including malondiadehycle (MDA) concentration, superoxide dismutate (SOD) activity, SOD mRNA and protein, behavior index (mouse water maze test and neurotransmitter ) and pathology (conventional pathology and immune histo-chemistry) were also determined. Results Compared with control group, humoral immunity of normal aging mice was obviously lower, but humoral immunity of D-galactose treated mice showed no difference. Compared with control group, SOD activity was higher and MDA concentration was lower in both D-galactose treated mice and normal aging mice. Behavior tests demonstrated that swimming time extended in different time phase in normal aging mice compare with control group, D-galactose treated group, however, showed no obvious difference. Adrenaline and tissue dopamine in brain tissue of normal aging mice decreased compared with control group, but D-galactose treated mice expressed no difference. And neurotransmitter changes were in accordance with behavior tests. The expression of SOD mRNA level, SOD activity and protein reduced in normal aging group and D-galactose group, compared with control group, which suggested that the downexpression of SOD mRNA was the main cause to the depressed SOD protein expreesion level and activity. Conclusion D-galactose treated mice were similar to natural aging mouse in some aspects, but there was still big difference between them in immunology and behavior index. D-galactose treated mice is caused by chemical damage and this model is hard to reflect real physiology and biochemistry changes, so it is not a ideal model for immunological and behavioral aging study.