苦参总黄酮对D-半乳糖致衰老小鼠的影响

Effect of flavonoids from Sophora flavescens in aging mice induced by D-galactos

该文研究了苦参总黄酮(flavonoids from Sophora flavescens)对D-半乳糖致衰老小鼠的影响,并探讨其作用机制。将60只小鼠随机分为对照组、模型组、脑复康组(阳性对照组)、苦参总黄酮低、中、高剂量组。采用D-半乳糖(160 mg·kg-1)颈背部皮下注射连续30 d建立亚急性衰老小鼠模型,造模同时,苦参总黄酮低、中、高剂量组分别灌胃苦参总黄酮(150,300,600mg·kg-1),连续30 d。采用跳台试验、避暗试验来检测小鼠的学习记忆能力,检测脑组织中丙二醛(MDA)、肿瘤坏死因子(TNF-α)含量与超氧化物歧化酶(SOD)、单胺氧化酶-B(MAO-B)、Na+-K+-ATP酶、Ca2+-ATP酶活性,检测血清中乳酸脱氢酶(LDH)的活性,并且HE染色,光镜下观察脑海马齿状回区组织结构的变化。结果发现,与模型组比较,苦参总黄酮中、高剂量组及脑复康组能明显延长避暗潜伏期、跳台潜伏期,苦参总黄酮各剂量组及脑复康组均减少避暗错误次数,苦参总黄酮高剂量组及脑复康组可减少跳台错误次数(P<0.05或P<0.01)。苦参总黄酮中、高剂量组及脑复康组能提高衰老小鼠脑组织中SOD和Na+-K+-ATP酶活性,降低脑组织中MAO-B的活性、MDA及TNF-α含量,降低衰老小鼠血清中LDH活性(P<0.05或P<0.01)。苦参总黄酮各剂量组及脑复康组脑组织中Ca2+-ATP酶活性增强,同模型组比较有统计学差异(P<0.05或P<0.01)。病理可见模型组海马齿状回细胞数目减少,细胞排列稀疏,细胞形态欠完整,胞浆稀少,胞核与胞浆界限欠清晰,细胞核深染,固缩不规则形,核仁不明显。苦参总黄酮组及脑复康组海马组织形态较模型组改善。可见,苦参总黄酮能改善D-半乳糖致衰老小鼠的学习记忆能力,其作用机制可能与通过减少TNF-α含量而增强抗氧化作用,从而稳定细胞膜、降低脑内MAO-B活性有关。

To investigate the effect of flavonoids from Sophora flavescens in aging mice induced by D-galactose and its mechanism.Totally 60 mice were randomly divided into six groups： the control group,the model group,the piracetam group（ positive control group） and flavonoids from S. flavescens low,medium and high doses groups. Except for the control group,all of the rest groups were subcutaneously injected with D-galactose（ 160 mg·kg- 1） for successively 30 days to establish the sub-acute senescent model. Meanwhile,flavonoids from S. flavescens low,medium and high doses groups were respectively administered with 150,300 and 600 mg·kg- 1of flavonoids from S. flavescens for 30 days. The learning and memory abilities of mice were determined by avoiding darkness experiment and jumping stair experiment. The contents of malondialdehyde（ MDA）,tumor necrosis factor-α（ TNF-α）,the activities of superoxide dismutase（ SOD）,monoamine oxidase-B（ MAO-B）,Na＋-K＋-ATPase and Ca2 ＋-ATPase in the brain of mice were determined respectively after the behavioral experiments. The activity of lactic dehydrogenase（ LDH） in blood serum was also determined and analyzed by microscope after HE staining to observe the changes in hippocampal organizational structure. Compared with the model group,flavonoids from S. flavescens medium and high doses groups showed significantly increases in the latency of avoiding darkness and jumping stair experiments; flavonoids from S. flavescens low,medium and high doses groups and the piracetam group showed decreases in the numbers of errors in avoiding darkness experiment; the flavonoids from S. flavescens high dose group and the piracetam group showed reduction in the number of errors in jumping stair experiment（ P 0. 05 or P 0. 01）. Flavonoids from S. flavescens medium and high doses groups and the piracetam group showed improvements in the activities of SOD,Na＋-K＋-ATPase in the brain of mice and declines in the contents of MDA and TNF-α,the activity of MAO-B in the brain of mice,the activity of LDH in blood serum（ P 0. 05 or P 0. 01）. Flavonoids from S. flavescens low,medium and high doses groups and the piracetam group also showed improvement in the activity of Ca2 ＋-ATPase,with statistical difference from the model group（ P 0. 05 or P 0. 01）. The pathological result showed decreases in the number of cells of hippocampal dentate gyrus area,sparse cell arrangement,incomplete cellular morphology,scarce cytoplasm,blurred boundary between nucleus and cytoplasm,nuclei anachromasis,irregular pyknosis and unconspicuous nucleoli in the model group. Compared with the model group,flavonoids from S. flavescens low,medium and high doses groups and the piracetam group showed improvements in hippocampal organization tissues. Flavonoids from S. flavescens can improve the learning and memory ability of senescent mice induced by D-galactose. Its mechanism may be correlated with the enhancement of anti-oxidative actions by lowering TNF-α content,which results in the stability of cell membrane and the reduction in MAO-B activity.