［Abstract］Objective： To investigate the protective effect of neural stem cell-conditioned medium (NSC-CM) on 6-hydroxydopamine (6-OHDA)-induced neuronal injury in vitro and in vivo model of Parkinson′s disease(PD) and its potential mechanisms. Methods： The in vivo PD model was established by stereotaxic injection of 6-OHDA into the medial forebrain bundle of SD rats, and NSC-CM was injected into the substantia nigra and striatum for treatment. The loss of dopaminergic neuron (DAN) in the substantia nigra and striatum was detected by immunohistochemical staining. The expression level of mitofusin 1 (Mfn1) in substantia nigra was detected by Western blotting; The PD cell model was established in vitro by treating rat adrenal medulla pheochromocytoma (PC12 cells) with 6-OHDA, and pretreated with NSC-CM. Lactate dehydrogenase (LDH) release and cellular reactive oxygen species (ROS) levels in PD cell model were detected, and the expression level of Mfn1 was detected by Western blotting. The components of NSC-CM were detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and analyzed by bioinformatics analysis. Flow cytometry and laser confocal microscopy were used to observe the internalization of neural stem cells (NSCs) mitochondria by PC12 cells. The effects of NSC-CM on the cell viability and mitochondrial fluorescence intensity of PC12 cells were compared before and after removal of mitochondria. Results： After injection of NSC-CM, the loss of DAN was significantly decreased and the expression level of Mfn1 protein was greatly increased in PD rats (P<0.05). After NSC-CM pretreatment, the release of LDH and the level of ROS in the PD cell model were significantly decreased (P<0.05), and the expression level of Mfn1 protein was remarkably increased (P<0.05). LC-MS/MS detected the presence of mitochondrial components in NSC-CM, and observed the internalization of mitochondria in NSC-CM by PC12 cells. Removal of mitochondria from NSC-CM significantly decreased the survival rate of PC12 cells (P<0.05) and the fluorescence intensity of mitochondria (P<0.05). Conclusion： NSC-CM could improve neuronal death, increased oxidative stress level and decreased mitochondrial fusion level caused by 6-OHDA, and this protective effect may be related to PC12 cells internalizing NSCs mitochondria.

Objective： To observe the effect of butylphthalide (NBP) on the expression of insulin-like growth factor 1 receptor (IGF1R) in hippocampus of APP/PS1/Tau mice, and to explore the mechanism of IGF1R in NBP treatment of Alzheimer′s disease (AD). Methods： Thirty 8-month-old male APP/PS1/Tau mice were randomly divided into AD group, NBP intervention group and NBP+IGF1R inhibitor intervention group, with 10 mice in each group. Ten 8-month-old C57BL/6J male rats were also taken as the control group. The control group and AD group were given 0.2 mL of vegetable oil by gavage daily, the NBP intervention group was given 120 mg/kg of NBP by gavage daily, and the NBP+IGF1R inhibitor intervention group was given 10 mg/kg of IGF1R inhibitor (NVP-ADW742) by intraperitoneal injection on the basis of the NBP intervention group. After 6 weeks of continuous administration, cognitive behavior of each group was detected by Y maze test, new object recognition test and water maze test. The expressions of Aβ, Tau and p-Tau in hippocampus were detected by Western blotting, Nissl staining was used to evaluate the damage of hippocampal neurons, and immunofluorescence was used to detect the expression of IGF1R in hippocampus. Results： Compared with AD group, NBP intervention group had higher spontaneous alternation rate, higher cognitive index (P<0.05), shorter escape latency of water maze and more times of crossing the platform (P<0.05). Compared with AD group, the protein Aβ and p-Tau in hippocampus of NBP intervention group decreased significantly (P<0.05), the apoptosis of hippocampal neurons decreased significantly (P<0.05) and the expression of IGF1R in hippocampus increased significantly (P<0.05). Compared with NBP intervention group, the expressions of Aβ and p-Tau protein in hippocampus of NBP+IGF1R inhibitor intervention group were higher (P<0.05), the spontaneous alternation rate and cognitive index were significantly decreased (P<0.05), the latency of water maze escape was remarkably prolonged (P<0.05), and the number of crossing platforms was remarkably reduced (P<0.05). Conclusion： NBP could protect AD by up-regulating the expression of IGF1R in hippocampus.

帕金森病(Parkinson′s disease，PD)是一种好发于中老年人的神经退行性疾病，表现为核心的运动症状和各种各样的非运动症状。其中，冻结步态是PD特征性运动症状之一。随着疾病进展，冻结步态的发生率逐渐增加，且药物治疗和外科治疗手段难以提供令人满意或持久的疗效，而康复治疗在一定程度上可帮助PD患者改善冻结步态。本文总结归纳了目前较为常见的康复治疗手段，并阐述其对冻结步态的治疗效果以及可能的作用机制，以期为PD患者制定个体化康复治疗方案予以参考。