目的 探讨灵芝制剂对APP/PS-1转基因阿尔茨海默病(AD)小鼠的病理学改变.方法 选用4月龄APP/PS-1转基因小鼠,分为AD模型组、灵芝高剂量[2250 mg/ (kg· d)]组和灵芝中剂量[750 mg/ (kg· d)]组,阳性对照组用盐酸多奈哌齐药物[2mg/ (kg·d)],正常组选用C57BL/6J野生鼠.动物给药4个月后解剖观察组织病理,应用苏木素-伊红(HE)染色、免疫组织化学、特殊染色及电子显微镜超微结构观察并比较各组组织病理形态及结构差异.结果 病理形态学改变:灵芝制剂组小鼠脑内老年斑降解、减少或消失;神经元纤维缠结减少或消失;淀粉样蛋白血管病明显减少;海马和齿状核的幼稚神经细胞数量比AD模型组显著增多(海马:F=1.738,P=0.016;齿状核:F=1.924,P=0.026);灵芝制剂高、中剂量组小鼠小脑浦肯野细胞较模型组丢失少(F=9.46,P=0.007;F=9.46,P=0.0l0);灵芝制剂组DCX免疫组织化学染色阳性显示小脑神经干细胞出现早而且数量多.电镜观察灵芝制剂组小鼠海马神经细胞较AD模型小鼠完整,核膜完好,胞质内的线粒体、内质网、高尔基体、微管结构、突触完整.小胶质细胞无异常.灵芝制剂治疗组小鼠在整个实验中未见到细胞和组织学的毒性表现.结论 灵芝制剂可使AD小鼠脑内老年斑和神经元纤维缠结降解、减少或消失及淀粉样蛋白血管病变减少.“,”Objective To explore the efficacy of ganoderma lucidum preparation (Ling Zhi) in treating APP/PS-1 transgenic mouse models of Alzheimer’ s disease (AD).Methods APP/PS-1 transgenic mice of 4 months were randomly divided into model group,ganoderma lucidum treatment groups,including high [2250 mg/ (kg· d)] and middle [750 mg/ (kg · d)] dose groups,i.e.LZ-H and LZ-M groups,and the positive control group (treated with donepezil hydrochloride [2 rmg/ (kg · d)]).In addition,C57BL/6J wild mice were selected as normal group.The animals were administered for 4 months.Histopathological examinations including hematoxylin-eosin (HE) staining,immunohistochemistry,special staining,and electron microscopy were applied,and then the pathological morphology and structures in different groups were compared.Results The senile plaques and neurofibrillar tangles in the cerebrum and cerebellum were dissolved or disappeared in LZ-H and LZ-M groups.Decrease of amyloid angiopathy was found in LZ-H and LZ-M groups.The immature neurons appeared more in hippocampus and dentate nucleus of LZ-H and LZ-M groups than those in AD model and donepezil hydrochloride groups (hippcampus:F =1.738,P =0.016;dentate nucleus:F =1.924,P =0.026),and these immature neurons differentiated to be neurons.More Purkinje cells loss occurred in AD model mice than that in LZ-H and LZ-M groups (F =9.46,P =0.007;F =9.46,P =0.010).The LZ-H and LZ-M groups had more new neuron stem cells grown up in cerebellum.Electromicroscopic examination showed the hippocampal neurons in LZ-H and LZ-M group were integrated,the nuclear membrane was intact,and the mitochondria in the cytoplasm,endoplasmic reticulum,Golgi bodies,microtubules,and synapses were also complete.The microglial cell showed no abnormality.No toxicity appeared in the pathological specimens of mice treated with ganoderma lucidum preparation.Conclusion The ganoderma lucidum preparation can dissolve and decline or dismiss the senile plaques and neurofibrillar tangles in the brain of AD mice and also reduce the amyloid angiopathy.