Qin Chuan, Wu Shan-Qiu, Chen Bao-Sheng, Wu Xiao-Xian, Qu Kun-Yao, Liu Jun-Min, Zhang Gui-Fang, Xu Yan-Feng, Shu Shunli, Sun Lihua, Li Yan-Yong, Zhu Hua, Huang Lan, Ma Chun-Mei, Xu Yu-Huan, Han Yun-Lin, Lu Yao-Zeng
Institute of Medical Laboratory Animal Science,Chinese Academy of Medical Sciences, Center of Comparative Medicine,Peking Medical College,Beijing 100021,China.
Mei Shan Tang Biotechnology(Shenzhen) Ltd,Shenzhen,Guangdong 518000,China.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2017 Aug 20;39(4):552-561. doi: 10.3881/j.issn.1000-503X.2017.04.015.
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 mg/(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.
目的 探讨灵芝制剂（灵芝）对阿尔茨海默病（AD）APP/PS-1转基因小鼠模型的治疗效果。方法 将4月龄的APP/PS-1转基因小鼠随机分为模型组、灵芝治疗组，其中灵芝治疗组又分为高剂量组[2250mg/(kg·d)]和中剂量组[750mg/(kg·d)]，即LZ-H组和LZ-M组，以及阳性对照组（用盐酸多奈哌齐[2mg/(kg·d)]治疗）。此外，选取C57BL/6J野生小鼠作为正常组。动物给药4个月。应用苏木精-伊红（HE）染色、免疫组织化学、特殊染色及电子显微镜等组织病理学检查，比较不同组的病理形态和结构。结果 LZ-H组和LZ-M组大脑和小脑的老年斑及神经原纤维缠结溶解或消失。LZ-H组和LZ-M组淀粉样血管病减轻。LZ-H组和LZ-M组海马和齿状核中出现的未成熟神经元比AD模型组和盐酸多奈哌齐组多（海马：F=1.738，P=0.016；齿状核：F=1.924，P=0.026），且这些未成熟神经元分化为神经元。AD模型小鼠浦肯野细胞丢失比LZ-H组和LZ-M组多（F=9.46，P=0.007；F=9.46，P=0.010）。LZ-H组和LZ-M组小脑中有更多新的神经干细胞生长。电镜检查显示LZ-H组和LZ-M组海马神经元完整，核膜完整，细胞质中的线粒体、内质网、高尔基体、微管及突触也完整。小胶质细胞未见异常。灵芝制剂处理的小鼠病理标本未出现毒性。结论 灵芝制剂可溶解并减少或消除AD小鼠脑中的老年斑和神经原纤维缠结，还可减轻淀粉样血管病。
