人参皂甙对老龄大鼠Meynert核及大脑皮质脑源性神经营养因子含量的影响

目的观察Meyaert核（NBM）与大脑皮质神经元内脑源性神经营养因子（BDNF）的老龄性改变,探讨人参皂甙对BDNF蛋白含量表达的影响.方法雌性Wistar大鼠随机分为青年组、老龄组及老龄给药组.老龄给药组大鼠自18个月开始饲以人参皂甙至27月龄.对各组NBM及大脑皮层神经元进行免疫组织化学法染色、图像分析及统计学处理.结果老龄组大鼠NBM及大脑皮质内BDNF含量均显著低于青年组（P＜0.01）.给药组大脑皮质内BDNF含量较老龄组显著增加（P＜0.01）,但NBM内BDNF含量变化无统计学意义.结论老龄大鼠NBM及大脑皮质内BDNF含量显著降低,给予人参皂甙可显著提高大脑皮质神经元BDNF的表达.     

人参皂甙对老龄大鼠大脑皮质AChE老龄性改变的影响

目的观察大鼠大脑皮质乙酰胆碱酯酶(AChE)阳性纤维的老龄性改变,探讨人参皂甙对其影响。方法24只雌性Wis青tar大鼠随机分为青年组、老龄组及给予人参皂甙的给药组。对各组大鼠大脑皮质进行AChE酶细胞化学染色,图像分析各组大鼠大脑皮质神经纤维AChE含量及AChE纤维的配布情况。结果老龄组大鼠大脑皮质神经纤维AChE平均光密度值较年组明显减少(p<0.01),AChE纤维面积百分比例下降,人参皂甙组大鼠大脑皮质神经纤维AChE平均光密度值较老龄组明显增加(p<0.01),纤维面积百分比例上升。结论人参皂甙可增加老龄大鼠大脑皮质纤维中AChE平均光密度值,促进纤维侧枝出芽和纤维网的生长及重建。     

人参皂甙降低老龄大鼠海马CA3区神经元酸性磷酸酶活性的光、电镜观察

实验选用健康的Wistar大鼠,应用光、电镜酶细胞化学方法结合图像分析观察了老龄大鼠海马CA3区神经元的酸性磷酸酶的衰老变化,同时对比观察了人参皂甙对上述改变的影响.光镜结果表明:酸性磷酸酶含量老龄组比青年组增加36%,而给药组较老龄组减少20%;电镜结果表明:酸性磷酸酶反应产物面积老龄组比青年组增加5倍,给药组较老龄组减少2.5倍(P<0.01).光、电镜结果均提示老龄时海马CA3区神经元酸性磷酸酶活性增高,而人参皂甙具有降低酸性磷酸酶活性的作用.     

人参皂甙对Alzheimer病模型大鼠海马生长抑素mRNA表达的影响

目的：研究人参皂甙（GS）对Alzheimer病（AD）模型大鼠海马内生长抑素（SS）mRNA表达的影响。方法：本实验以D-半乳糖致衰老合并鹅膏蕈氨酸脑内Meynert核注射建立AD大鼠模型,运用原位杂交方法结合图像分析检测各组大鼠海马SSmRNA表达。结果：模型组大鼠海马各区SSmRNA表达阳性神经元平均灰度值比正常对照组明显升高,平均密度显著降低;而预防组、治疗组阳性神经元灰度值则比模型组显著降低,平均密度明显升高;正常对照组与人参皂甙对照组大鼠的CA4及DG区中,此两项指标差异显著。结论：GS对AD模型大鼠海马SSmRNA表达减弱有预防及治疗作用。     

人参皂甙降低老龄大鼠海马CA3区神经元酸性磷酸酶活性的光,电镜观察

实验选用健康的Ｗｉｓｔａｒ大鼠，应用光、电镜酶细胞化学方法结合图像分析观察了老龄大鼠海马ＣＡ３区神经元的酸性磷酸酶的衰老变化，同时对比观察了人参皂甙对上述改变的影响。光镜结果表明：酸性磷酸酶含量老龄组比青年组增加３６％，而给药组较老龄组减少２０％；电镜结果表明：酸性磷酸酶反应产物面积老龄组比青年组增加５倍，给药组较老龄组减少２．５倍（Ｐ〈０．０１）。光、电镜结果均提示老龄时海马ＣＡ３区神经元酸性磷     

人参皂甙对老龄大鼠海马CA3区神经元超微结构影响的定性,定量研究

应用透射电镜技术结合图像分析观察了老龄大鼠海马ＣＡ３区神经元超微结构的改变，并对比观察了人参皂甙对超微结构的影响，结果表明：老龄组社会脂褐素数量比青年组增加６倍，面积增加９倍；而给药组脂褐素数量比老龄 组减少，面积减少３１％。     

人参皂甙对老龄大鼠海马CA3区神经元超微结构影响的定性、定量研究

应用透射电镜技术结合图像分析观察了老龄大鼠海马CA_3区神经元超微结构的改变,并对比观察了人参皂甙对超微结构的影响.结果表明:老龄组神经元脂褐素数量比青年组增加6倍(P<0.01),面积增加9倍(P<0.01);而给药组脂褐素数量比老龄组减少18%(P<0.05),面积减少31%(P<0.05).此外,老龄组神经元内线粒体等细胞器出现明显变性、坏死、突触变性,神经毡内出现髓样体,膜性结构等异常改变;而给药组上述改变均见明显减轻或不出现.     

人参皂甙对急性肾衰大鼠中缝正中核和中缝背核5-HT含量的影响

目的:本研究选用甘油致急性肾衰(ARF)动物模型,探讨口服人参皂甙(GS)对ARF大鼠中缝正中核(MRN)和中缝背核(DRN) 5-羟色胺(5-HT)含量变化的影响。方法:64只健康雄性SD大鼠,随机分为4组:模型组、模型给药组、空白对照组和空白给药组。肌肉注射甘油制备急性肾衰模型,利用商品化试剂盒检测口服人参皂甙48 h后各组大鼠血尿素氮(BUN)和肌酐(Cre)的变化;同时用免疫组化方法观察MRN和DRN 5-HT免疫反应活性(5-HT-IR)变化。结果:肾功能检测显示模型对照组血清BUN和Cre水平显著升高,模型给药组血清BUN和Cre水平显著下降。免疫组化的实验显示ARF大鼠MRN 5-HT-IR增强,DRN 5-HT-IR减弱;人参皂甙能明显阻断ARF诱导的上述变化。结论:人参皂甙处理能够减少ARF大鼠MRN 5-HT含量,增加DRN 5-HT的含量,人参皂甙对MRN和DRN内5-HT能神经元活性的差异调节可能是人参皂甙抗急性肾衰和保护肾功能的中枢神经元机制之一。     

大鼠下丘脑内前阿黑皮素原mRNA的老年变化

研究大鼠下丘脑内前阿黑皮素原（POMC）mRNA表达的老年变化，本实验采用SPraque－Dawley大鼠3月龄（青年组）和28～30月龄（老年组）各8只，利用地高辛标记POMC反义RNA探针进行原位杂交组织化学并行图象定量分析。结果：在青年组大鼠肉，OPMCmRNA阳性胞体主要分布于弓状核及其邻近区域；老年大鼠POMCmRNA胞体主要分布于弓状核的内侧，着色浅谈．与年轻大鼠相比，老年大鼠下丘脑内POMCmRNA神经元数量显著减少，（P＜0．01），胞体灰度值明显升高（P＜0．05），而胞体截面积略有增大，但差异无显著性（P＞0．05）。结果表明，大鼠下丘脑内POMCInRNA神经元有明显的老年变化，提示老年大鼠下丘脑POMC神经元胞体发生了衰老形态学改变，功能活动低下，细胞丢失，POMC的表达显著增加，生物合成功能紊乱。     

老年性记忆减退大鼠内侧隔核突触结构的改变

取老年记忆减退组 (简称减退组 )、老年记忆正常组 (简称正常组 )和青年组大鼠内侧隔核进行透射电镜观察。证明 :减退组内侧隔核中突触数密度较青年组和正常组分别下降了 45 .2 7%和 44.16% ( P<0 .0 1) ;突触连接带平均面积 :减退组较青年组显著增加 ( P<0 .0 5 ) ;突触连接带面密度 :减退组较青年组和正常组分别下降了 3 5 .2 9和 3 3 .3 3 ( P<0 .0 1) ;突触的体密度 :减退组较青年组和正常组分别下降了 46.98和 49.68 ( P<0 .0 1)。统计结果表明 :受试大鼠的逃避潜伏期与突触数密度、突触连接带面密度、体密度呈明显负相关 ( r=-0 .8943 ,P<0 .0 1;r=-0 .80 0 7,P<0 .0 1;r=-0 .90 17,P<0 .0 1) ;与突触连接带平均面积呈显著正相关 ( r=0 .62 73 ,P<0 .0 5 )。还证明减退组大鼠含线粒体的突触百分比、突触前体内突触小泡数都有大幅度下降 ;正常组的含线粒体突触的百分比、突触小泡数较青年组也有减少。本研究结果提示 :减退组大鼠内侧隔核突触发生退行性变 ,此改变可能是老年性记忆减退的突触学基础     

Spatial memory training modifies the expression of brain-derived neurotrophic factor tyrosine kinase receptors in young and aged rats

Aging leads to alterations in the function of the hippocampus, a brain structure largely involved in learning processes. This study aimed at examining the basal levels and the impact of a learning-associated task on brain-derived neurotrophic factor (BDNF), on BDNF full-length catalytic receptor (TrkB.FL) and on the truncated forms (TrkB.T1 and TrkB.T2) receptor expression (mRNA and protein) in the hippocampus of young (2-month-old) and aged (24-month-old) Wistar rats. Spatial memory was evaluated using a water-maze procedure involving visible and invisible platform location learning. Aged rats showed higher latencies during the first two training days but rapidly exhibited learning performances similar to patterns observed with young rats. Real-time PCR measurements showed that aged rats had significantly higher levels of trkB.FL mRNAs than young rats under basal conditions. In situ hybridization analysis indicated that the highest level of trkB.FL mRNA (mRNA encoding for TrkB.FL receptor) was noted in the dentate gyrus, and in the CA2 and CA3 hippocampal layers. In contrast, there was no marked difference in trkB.T1 signal in any hippocampal region. Training induced a significant reduction in trkB.FL mRNA levels solely in aged rats. In contrast, in young and aged rats, trkB.T2 mRNA levels were significantly increased after training. Measurements of proteins revealed that learning significantly increased TrkB.FL content in aged rats. Untrained aged rats presented higher levels of BDNF and brain-derived neurotrophic factor precursor (proBDNF) proteins than young rats. Training strongly increased precursor BDNF metabolism in young and aged rats, resulting in increased levels of proBDNF in the two groups but in old rats the mature BDNF level did not change. This study shows that Wistar rats present age-related differences in the levels of BDNF and TrkB isoforms and that spatial learning differentially modifies some of these parameters in the hippocampus.     

大鼠体神经-内脏神经吻合后脑源性神经营养因子及其受体的表达变化

为了研究大鼠体神经-内脏神经吻合后脑源性神经营养因子(BDNF)及其受体酪氨酸激酶B(TrkB)在脊髓前角神经元中的表达变化,以正常大鼠为对照,运用RT-PCR技术检测大鼠体神经-内脏神经吻合术后不同时间脊髓腰4(L4)前角神经元中BDNF及TrkB mRNA的表达变化。结果显示,在正常大鼠L4前角神经元中,BDNF及TrkB的mRNA均存在一定水平的表达;体神经-内脏神经吻合术后7d、14d、1m和2m,BDNF和TrkBm RNA的表达均升高,术后7d达到高峰,14d开始下降;2m时BD-NF mRNA的表达量仍显著高于正常组(P<0.01),而TrkB mRNA的表达量到2m时虽仍高,但与正常组相比,其差异已无统计学意义(P>0.05)。上述结果表明,大鼠体神经-内脏神经反射弧建立后,脊髓L4前角神经元的内源性BDNF及其受体TrkB的表达均增高,它们可能作为保护性因子有利于受损神经元的存活和再生。     

Age-related loss of galanin-immunoreactive cells in the rat septal area

We have examined the distribution of galanin-like immunoreactive (LI) cell bodies in the medial septal nucleus (MS) and the nucleus of the diagonal band of Broca (nDBB) of young (3 months) and aged (25-30 months) rats, and assessed their respective contribution to the septohippocampal pathway. Immunohistochemical techniques were used alone or combined with the retrograde transport of a protein-gold complex injected into the dorsal hippocampus. In both groups, galanin-LI cells were observed in the MS and the nDBB. In aged rats, a significant decrease in both the staining intensity and the number of galanin-LI perikarya throughout the MS-nDBB complex was observed. Some immunoreactive cells appeared shrunken. The reduction in cell number ranged from 30 to 85%. There was also a decrease in the proportion of septohippocampal neurons containing galanin in aged rats (13% vs 20% in young animals) which however did not reach statistical significance. These results suggest that galanin-positive cells in the medial septal area undergo alterations with aging in the rat.     

大鼠杏仁中央核神经紧张肽和强啡肽神经元的年龄变化及牛膝的干预作用-免疫组织化学及图像定量分析研究

采用免疫组织化学ABC法结合图像定量分析观察杏仁中央核内神经紧张肽和强啡肽标记神经元的年龄变化及牛膝的抗衰老作用.结果:神经紧张肽神经元随月龄增加呈现细胞数减少、细胞面积增加和灰度值增大(P<0.05),22月龄大鼠发现有形态改变.强啡肽神经元左右两侧不同步变化,左侧在9月龄呈现细胞数减少,细胞面积增加、灰度值增大(P<0.05),在22月龄还可见形态改变;右侧在22月才出现细胞数减少、细胞面积增加、灰度值增大(P<0.05),未见明显的形态改变.牛膝喂药组与同月龄大鼠相比,神经紧张肽和强啡肽神经元的细胞数减少、细胞面积增加和灰度值的增大均降低(P<0.05),未见明显的形态改变,证实牛膝有延缓衰老之功效.     

Editorial

Aims: Ageing impairs endothelial function such as the regulation of vascular tone. The release of nitric oxide (NO), which has a potent vasodilator effect and antiatherosclerotic property, is decreased in the aorta of aged rats. Exercise training, however, has been reported to increase the expression of endothelial NO synthase (eNOS) in the aorta of young rats. In aged rats, it is not known whether the expression of eNOS is altered by exercise training. We hypothesized that exercise training would improve the ageing‐induced decrease in eNOS expression in vessels, and examined the messenger RNA (mRNA) and protein expression of eNOS in the aorta of sedentary‐young rats (sedentary‐young group; 4 months old), sedentary‐aged rats (sedentary‐aged group; 23 months old), and swim‐trained aged rats (training‐aged group; 23 months old, swimming training for 8 weeks, 5 days week^?1, 90 min day^?1). Results: Body weight was significantly lower, and citrate synthase activity in the epitrochlearis muscle was significantly higher in the training‐aged group compared with the sedentary‐aged group. The mRNA expression of eNOS in the aorta was significantly higher in the training‐aged group than in the sedentary‐aged group, while it was significantly lower in both the sedentary‐aged and training‐aged groups than in the sedentary‐young group. The expression of eNOS protein in the aorta was also significantly higher in the training‐aged group than in the sedentary‐aged group, while it was also significantly lower in the sedentary‐aged group, but not in the training‐aged group, than in the sedentary‐young group. Conclusion: The present results revealed that the production of eNOS in the aorta decreases with ageing, and that the decreased production is increased by exercise training in aged rats, which may produce beneficial effects on the impaired cardiovascular system caused by ageing.     

BDNF-induced LTP in dentate gyrus is impaired with age: analysis of changes in cell signaling events

Brain-derived neurotrophic factor (BDNF) has emerged as a major regulator of synaptic plasticity in the adult brain and acute BDNF infusion has been shown to trigger long-term potentiation (BDNF-LTP) in adult rats. Here we compared the effects of acute BDNF infusion in young adult and aged anesthetized rats. In young rats, BDNF-LTP was accompanied by increased activation of the BDNF receptor TrkB, and extracellular signal-regulated kinase (ERK), as well as enhanced evoked release of glutamate in synaptosomes prepared from DG. In aged rats, both BDNF-LTP and the associated signaling were significantly impaired, while analysis of untreated hippocampal tissue from aged rats showed that activation of TrkB and ERK were decreased. In addition to effects in the DG, BDNF-LTP was accompanied by robust phosphorylation of the calcium/cAMP-responsive element binding protein (CREB) in tissue prepared from entorhinal cortex of both young and aged rats. These results suggest a cascade of presynaptic changes contributing to the expression of BDNF-induced LTP and show that BDNF-induced transduction mechanisms are attenuated with age.     

Quantitative histochemistry of brain acetylcholinesterase and learning rate in the aged rat

Using a newly developed method for quantitative acetylcholinesterase (AChE) histochemistry we find a substantial decrease in AChE content in aged rats compared to young controls in the cholinergic cell body regions (the ventral pallidum and the medial septal nuclei) and, to a smaller extent in the projection areas (the cortex and hippocampus). In the same group of aged rats we find a severe deficit in the acquisition of a water maze task. Quantitative histochemistry is a potent method for detecting localized changes in AChE content in otherwise intact, learning-impaired aged rats.     

多重脑震荡大鼠5-羟色胺能神经纤维变化

目的:研究多重脑震荡(MCC)与大鼠认知记忆相关脑区5-羟色胺(5-HT)能神经纤维变化的规律,以探讨MCC大鼠认知行为障碍的神经生物学基础。方法:应用自制单摆式机械打击装置构建MCC大鼠模型,免疫组织化学及半定量方法研究MCC后大鼠5-HT能神经纤维的变化。结果:前额叶皮质、中隔区、丘脑、海马CA1和CA3区5-HT能神经纤维免疫反应阳性物在伤后2d组反应达高峰,杏仁体、海马CA2和CA4区在伤后4d组免疫反应了阳性最强;顶叶皮质、梨状皮质及伏隔核内侧在伤后8d组反应最强。5-HT纤维密度在中隔区和伏隔核内侧以伤后2d最高,杏仁体区以伤后1d最高,大脑皮质和丘脑5-HT纤维密度在伤后各损伤组与对照组相比无显著性差异。结论:MCC可引起与认知功能有关脑区的5-HT表达增高,5-HT的高表达可能由脑损伤后神经元过度兴奋所引起的神经递质紊乱造成,而这种紊乱可能影响大鼠的认知功能。