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针刺改善阿尔茨海默病模型小鼠脑内微环境及海马神经干细胞移植治疗的研究

Acupuncture Improves Cerebral Microenvironment in Mice with Alzheimer's Disease Treated with Hippocampal Neural Stem Cells.

机构信息

First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China.

Tianjin Key Laboratory of Acupuncture and Moxibustion, Tianjin, 300193, China.

出版信息

Mol Neurobiol. 2017 Sep;54(7):5120-5130. doi: 10.1007/s12035-016-0054-5. Epub 2016 Aug 24.

DOI:10.1007/s12035-016-0054-5
PMID:27558235
Abstract

Transplantation with neural stem cells (NSCs) is a promising clinical therapy for Alzheimer's disease (AD). However, the final fate of grafted NSCs is mainly determined by the host microenvironment. Therefore, this study investigated the role of Sanjiao acupuncture in the NSCs-treated hippocampus of a mouse model, senescence-accelerated mouse prone 8 (SAMP8) using Western blot, real-time fluorescent PCR, and immunofluorescence techniques. Meanwhile, we developed a co-culture model of hippocampal tissue specimens and NSCs in vitro, to observe the effects of acupuncture on survival, proliferation and differentiation of grafted NSCs using flow cytometry. Results showed that acupuncture pre- and post-NSCs transplantation significantly improved senescence-induced cognitive dysfunction (P < 0.05); upregulated the expression of basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), and brain-derived neurotrophic factor (BDNF) (P < 0.05); and also increased the count of neuron-specific nuclear protein (NeuN)- and glial fibrillary acidic protein (GFAP)-positive cells (P < 0.05). Therapeutic acupuncture may regulate the cytokine levels associated with survival, proliferation, and differentiation of NSCs in hippocampal microenvironment, to promote the repair of damaged cells, resulting in improved cognitive performance in mice.

摘要

神经干细胞(NSCs)移植是治疗阿尔茨海默病(AD)的一种很有前途的临床疗法。然而,移植的 NSCs 的最终命运主要取决于宿主的微环境。因此,本研究采用 Western blot、实时荧光 PCR 和免疫荧光技术,探讨了三焦针刺在 NSCs 处理的 SAMP8 小鼠模型(衰老加速小鼠 8 号品系)海马中的作用。同时,我们在体外建立了海马组织标本和 NSCs 的共培养模型,通过流式细胞术观察针刺对移植 NSCs 的存活、增殖和分化的影响。结果表明,NSCs 移植前后针刺可显著改善衰老诱导的认知功能障碍(P<0.05);上调碱性成纤维细胞生长因子(bFGF)、表皮生长因子(EGF)和脑源性神经营养因子(BDNF)的表达(P<0.05);并增加神经元特异性核蛋白(NeuN)和神经胶质纤维酸性蛋白(GFAP)阳性细胞的计数(P<0.05)。治疗性针刺可能调节与 NSCs 存活、增殖和分化相关的细胞因子水平,促进受损细胞的修复,从而改善小鼠的认知表现。

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