异菝葜皂甙元及多奈哌齐对大鼠脑神经营养因子和胆碱乙酰转移酶的影响  

A comparative study of the effect of smilagenin and donepezil on BDNF content and ChAT activity in brains of aged rats

作　　者：王子玫[1] 孙启祥[1] 夏宗勤[1] 胡雅儿[1] 

机构地区：[1]上海交通大学医学院细胞调控研究室,200025

出　　处：《中华老年医学杂志》2007年第4期289-292,共4页Chinese Journal of Geriatrics

基　　金：国家自然科学基金（30371636）

摘　　要：目的平行对比观察知母皂甙元25位异构体异菝葜皂甙元（SMI）与胆碱酯酶抑制剂多奈哌齐（DN）对自然衰老大鼠行为学及脑毒蕈碱样胆碱受体（M受体）、脑源性神经营养因子（BDNF）水平和胆碱乙酰转移酶（ChAT）阳性神经元的影响，探讨SMI的作用机制。方法20月龄SD大鼠随机分为老年对照组、SMI组、DN组及SMI＋DN合并用药组，另设SD青年对照组。30d、60d及90d后用Y型电迷路评价大鼠学习记忆能力，放射配给结合法测乙酰胆碱M受体密度，酶联免疫吸附方法测BDNF含量，Fonnun法测ChAT活性，免疫组化法测大鼠不同脑区ChAT阳性神经元密度。结果老年鼠和青年鼠比较，学习记忆能力、脑内乙酰胆碱M受体密度[（1144±124）fmol／mg蛋白和（907±109）fmol／mg蛋白]、BDNF水平[（2．17±0．15）pg／mg蛋白和（1．36±0．14）pg／mg蛋白]和ChAT活性[（16．38±3．06）nmol·h^-1·mg^-1和（6．29±1．94）nmol·h^-1·mg^-1]显著降低（P〈0．05，P〈0．01）。老年鼠喂服SMI后，上述各指标均有显著改善[（1029±107）fmol／mg蛋白、（1．69±0．15）pg／mg蛋白和（10．18±1．47）nmol·h^-1·mg^-1，P〈0．05，P〈0．01]。老年鼠喂服DN后，学习能力改善，但长期记忆能力改善不显著，脑乙酰胆碱M受体密度和BDNF含量无增加，ChAT活性增加[（10．18±1．47）nmol·h^-1·mg-1]。海马、基底前脑斜角带核和Meynert基底核的ChAT阳性神经元密度检测结果，老年鼠显著低于青年鼠，SMI使该3个脑区都显著增加，DN仅使海马增加。结论SMI与胆碱酯酶抑制剂的药理作用机制不相同。SMI长期疗效明显好于胆碱酯酶抑制剂，SMI能延缓神经退行性变化的进程，可能是它改善学习记忆功能的重要机制之一。Objective To compare the effects of smilagenin （SMI） and donepezil （DN） on brain-derived neurotrophic factor （BDNF） and choline acetyltransferase （CHAT） activity in brains of aged rats and to probe the mechanism of SMI-treating memory impairment. Methods Aged rats were randomly divided into four groups： aged control, SMI, DN, SMI＋DN groups. Young SD rats were added as normal control group. The drugs were administered through gastric tube for 90 days in each group. The function of learning and memory was detected by Y-maze. ^3H-QNB single point combination was used to measure muscarinic acetylcholine receptor （M receptor） density of brain. BDNF content in brain was determined by ELISA. The Leventor＇s radiochemical method was used for estimating choline acetyltransferase. Using immunohistochemical staining, the normal morphology and distribution of the choline acetyltransferase-positive （CHAT） cells were examined in brain slices. Results The learning and memory ability were impaired in aged rats. Either SMI and, DN alone, or combined use of both improved the learning ability and memory significantly in the early stage. However, in the later stage, the effect of DN alone dropped down while the effect of SMI remained unchanged. The BDNF content, M recetpor density and ChAT activity of whole brain were lowered in aged rats when compared with those of young rats, and increased to a higher level in SMI group. DN improved learning ability but the long - term memory ability in this group dropped down gradually.The BDNF content and M receptor density of the whole brain were unchanged in DN group. While SMI elevated the activity of both pre-synaptic （diagonal band and nucleus basalis of meynert） and post-synaptic （hippocampus） cholinergic neurons, DN only elevated the activity of post-synaptic neurons. Conclusions The effect of SMI is better than cholinesterase inhibitor after long term treatment, and probably due to the fact that SMI has an neuron-protection effect.

关 键 词：知母皂苷 胆碱酯酶抑制剂 脑源性神经营养因子 乙酰基转移酶类 

分 类 号：R686[医药卫生—骨科学]