绞股蓝皂甙对痴呆小鼠学习记忆能力影响及机制

Effect and mechanism of Gynostemma pentaphyllum Makino on learning and memory ability in dementia mice

目的探讨绞股蓝皂甙(GPM)改善痴呆小鼠学习记忆能力的作用及机制。方法使用D-半乳糖联合亚硝酸钠、三氯化铝复制老年性痴呆(SDAT)小鼠模型,随机分为6组:对照组、模型组、GPM 50、150、250 mg/kg组、多奈哌齐组(阳性对照);连续给药3个月,采用水迷宫检测各组小鼠学习记忆能力、试剂盒法检测小鼠脑组织中抗氧化指标及β-淀粉样前体蛋白(APP)含量。结果与对照组比较,模型组小鼠潜伏期及首次穿越平台时间[分别为(18.76±2.32)、(15.27±1.42)s]延长,在原平台活动时间[(6.08±1.17)s]缩短;与模型组比较,GPM250 mg/kg组小鼠潜伏期、首次穿越原平台时间[分别为(7.58±1.93)、(8.17±0.68)s]明显缩短,在原平台活动时间[(12.55±2.07)s]延长。与对照组比较,模型组小鼠脑组织中超氧化物歧化酶(SOD)、谷胱甘肽过氧化酶(GSH-Px)活力[分别为(200.91±28.28)、(3.89±0.71)U/mg]明显下降,丙二醛(MDA)水平[(6.51±0.63)nmol/mg]上升;与模型组比较,GPM 250 mg/kg组小鼠脑组织中SOD、GSH-Px活力[分别为(305.97±98.65)、(11.62±2.52)U/mg]明显上升,M DA水平[(2.29±0.95)nmol/mg]下降,差异有统计学意义(P<0.01)。与对照组比较,模型组小鼠脑组织中s APPα表达[(1.869±0.12)ng/g]下降,Aβ_(42)表达[(6.668±0.647)μg/g]升高;与模型组比较,GPM 250 mg/kg组小鼠脑组织中s APPα[(2.097±0.11)ng/g]升高,Aβ_(42)[(5.812±0.632)μg/g]下降,差异有统计学意义(P<0.01)。结论绞股蓝皂甙具有改善痴呆小鼠的认知能力作用,其机制可能与其减轻脑组织抗氧化损伤、减少Aβ表达有关。

Objective To investigate the effect and mechanism of Gynostemma pentaphyllum Makino （GPM） on learning and memory ability in dementia mice. Methods We reproduced the model of mice with senile dementia of the Alzheimer type （SDAT） using D-galactose combined with sodium nitrite and aluminum muriate and then divided the model mice randomly into 6 groups ： a control group, a model group, three groups of GPM at dosages of 50,150, and 250 mg/kg, and a donepezil group （positive control）. After continuous treatments for 3 months, the learning and memory ability of the mice was assessed with water maze test and the contents of antioxidants and [3-amyloid precursor protein （APP） in brain of the mice were detected with reagent kit method. Results Compared with those of the control group, the latency （ 18.76 ±_ 2. 32 s） of and the time （ 15.27 ± 1.42 s） crossing the platform for the first time of the model mice prolonged,while the time of activity in original platform （6.08 ± 1.17 s） shortened. Compared with those of the model group,the latency （7.58 ± 1.93 s） of and the time （8.17 ±0. 68 s） crossing the platform for the first time of the mice treated with 250 mg/kg GPM decreased obviously but the time of activity in original platform （ 12. 55 ± 2. 07 s） lengthened. Compared with those of the control group,the activity of superoxide dismutase （SOD） （200. 91 ± 28.28 U/mg） and glu- tathione peroxidase （GSH-Px） （3.89 ± 0. 71 U/mg） in brain tissues of the model mice decreased significantly, and the level of malondialdehyde （MDA） （6.51 ± 0. 63 nmol/mg） increased. Compared with those of the model group, the ac- tivity of SOD （305.97±98.65 U/rag） and GSH-Px （ 11.62 ±2. 52 U/rag） in brain tissues of the mice treated with 250 mg/kg GPM increased significantly, and the level of MDA （2. 29 ± 0. 95 nmol/mg） decreased, with significant differ- ences （P 〈 0. 01 for all）. Compared with those of the control group, the expression of of secretase form of soluble amy- loid precursor protein （sAPPo） （1. 869 ±0. 12 ng/g） in brain tissues of the model mice decreased and the expression of amyloid-beta-42 （A42） （6. 668 ±0. 647μg/g） increased. Compared with that of the model group,the sAPPo （2. 097 ± 0. 11 ng/g） increased but A[42 （5.812 ±0. 632 μg/g） decreased in brain tissues of the mice treated with GPM, with sig- nificant differences （both P 〈 0. 01 ）. Conclusion Gynosaponin can improve cognitive ability in dementia mice and its mechanism may be related to the reduced antioxidant damage and Aβ expression in brain tissues.