PET显像监测中药复智散治疗阿尔茨海默病大鼠疗效的可行性研究

目的 研究PET技术评价中药复智散（FZS）治疗自然老化阿尔茨海默病（AD）大鼠疗效的可行性。方法采用中药FZS治疗10只AD大鼠模型30d后，通过Morris水迷宫测试大鼠行为学改变；另10只AD大鼠以蒸馏水连续30d灌胃，作为对照组，10只正常成年大鼠作为空白对照组。所有大鼠分别行18F-脱氧葡萄糖（FDG）、2-（4＇-N-11C-甲胺基苯）-6-羟基苯并噻唑（PIB）PET脑显像，并取脑组织样本行HE染色、β淀粉样蛋白（AB）免疫荧光、5-溴-2-脱氧尿嘧啶核苷（BrdU）免疫荧光和神经元核心抗原（NeuN）免疫荧光染色。采用SPSS13．0软件对行为学测试结果行配对t检验。结果FZS治疗后AD大鼠行为学较AD对照组有明显改善，药物治疗组AD大鼠潜伏期[（32．5±10．8）s]明显短于AD对照组[（102．6±8．8）s]（t=15．7987，P=0．000t），PET显像显示治疗后AD大鼠脑内葡萄糖代谢有所改善，而淀粉样物质的显像未见明显好转，该结果与病理结果一致。结论PET显像可作为在体评价AD疗效的一种手段；中药FZS可以通过增加神经细胞的增殖和存活而改善老年大鼠的记忆能力。

Therapeutic effects of FuZhiSan on Alzheimer's disease rat model:evaluation with PET imaging

Objective To assess the feasibility of using PET molecular imaging to evaluate the therapeutic effects of traditional Chinese medicine FuZhiSan (FZS) on the model of aging Alzheimer's disease (AD) rats. Methods Twenty aged AD rats (Sparague-Dawley rats,male) were randomly divided into FZS treated group (n = 10) and control group (n = 10). Another 10 healthy adult rats were as blank controls. Morris water maze record system was used for cognitive function assessment. Before and after FZS treatment 18 F-fluorodeoxyglucose (FDG) and 11 C-2- [4'-(methylamino) phenyl] benzothiazol-6-ol ( PIB )PET imaging was undertaken. After post-treatment imaging procedures the brain tissues of all animals were taken for histochemical study,such as staining with HE,congo red,amyloid β (Aβ) immunofluorescence,5-bromo-2-deoxyuridine (BrdU) immunofluorescence and NeuN immunofluorescence. Paired t-test was performed with SPSS 13.0 software for the data analysis. Results The cognitive dysfunction of aging AD rats was improved after FZS treatment. The escape latency in FZS treated group was significantly shorter than that of control group ((32.5 ±10.8) s vs (102.6±8.8) s,t =15.7987,P=0. 0001). Diffuse neuronal loss and Aβ deposition were detected in the hippocampus and cortex in the aged AD rats. The imaging data showed that brain glucose metabolism was amended in FZS treated group while the abatement of amyloid deposition was not significant. Immunofluorescence results indicated that the neuronal proliferation was more remarkable in FZS treated group. Conclusions It may be feasible to use PET imaging as a method to evaluate the therapeutic effect in AD rats. FZS may ameliorate memory dysfunction of aged AD rats. Its mechanism may be partly contributed to the enhancement of the neuronal proliferation and survival.