TA9902对SAM-P/8小鼠脑胆碱乙酰转移酶神经元的影响

Effect of TA9902 on Choline Acetyltransferase Neurons in Senescence-accelerated Mouse

目的 探讨抗氧化剂TA990 2 (TA990 1配伍EGb76 1)对加速老化鼠P/ 8(SAM P/ 8)脑胆碱乙酰转移酶 (ChAT)神经元的影响 ,为治疗阿尔采默病 (AD)提供理论依据。方法 选用 3月龄雄性SAM P/ 8小鼠 83只 ,随机分为TA90 0 1组、TA990 2低剂量组、TA990 2高剂量组、EGb76 1组、HAT组和老年组 ;另选 3月龄 15只为年轻组。对隔区切片用胆碱乙酰转移酶 (ChAT)免疫组化染色 ,并对ChAT阳性神经元进行计数和图像分析。结果 老年SAM P/ 8小鼠内侧隔核 斜角带 (MS DB)区ChAT神经元明显受损。TA990 2对MS DB区ChAT受损害神经元有显著改善作用 ,主要表现在ChAT神经元数量的增加和平均灰度值的下降 ,尤以高剂量组明显 ,这种改善作用虽有优于对照药HAT的趋势 ,但与HAT无显著性差异。相关分析结果表明ChAT阳性神经元数量与小鼠避暗试验测得的STL和STS分别呈显著正相关和负相关 (P <0 .0 5或P <0 .0 1)。结论 TA990 2有促进SAM P/ 8鼠脑受损胆碱能系统恢复的作用 ,这可能是其改善SAM P/

Objective To explore the effect of antioxidants TA9902(TA9901 matched EGb761) on choline acetyltransferase neuron(ChAT) in senescence accelerated mouse (SAM P/8) and provide scientific basis for TA9902's clinical use. Method Eighty three male SAM P/8 (3 months) were randomly divided into six groups, TA9901, EGb761, Low dose TA9902 (TA9902 L), High dose TA9902 (TA9902 H), Hat (Hup A), Old age group and young age group (3 months). The animals were fed for 6 to 6.5 months with normal diet. The morphological and quantitative changes of ChAT ir neurons in medial septum diagonal band(MS DB) of SAM P/8 mice were studied with immunohistochemical ABC method. Results The ChAT ir neurons appeared vacuolated and shrunken, and the neuropil was markedly reduced in MS DB complex of the old SAM P/8 mice. The number of ChAT ir neurons of MS DB reduced distinctly, and the mean area of somata of MS DB decreased distinctly as well with the increased gley value compared with that of young group. In TA9902 and Hup A groups, the number of ChAT ir neurons in MS DB increased remarkably with the decreased averge grey value compared with old group. In TA9902 H group, the number and mean area of somata obviously increased compared with old group and the effect was better than in Hup A in some MS DB complex. There was a positive correlation between the STL of ST test and the number of ChAT ir neuron and a negative correlation between the STS of STtest and numberof ChAT neurons in MS DB complex of examined mice respectively. Conclusion The results suggest that the TA9902 can enhance the function of cholinergic system, and it maybe one of the neurobiological mechanisms of neuronal protection for TA9902 to improve learning and memory function of the SAM P/8 mice.