锂对造血干细胞和神经干细胞作用影响的研究进展

doi:10.3877/cma.j.issn.2095-1221.2018.06.008

锂在现代精神病学中使用超过65年，其构成了双相情感障碍（BD）长期治疗的基础。锂的许多生物学特性已经被证实，包括抗病毒、血液系统和神经系统保护作用。本文系统综述了锂对造血干细胞（HSCs）、神经干细胞（NSCs）以及诱导多能干细胞（iPSCs）作用影响的研究进展及其目前已证实的分子机制。自20世纪70年代以来，锂对保持HSCs和生长因子高水平的作用已被报道。锂可以改善HSCs的归巢能力、形成菌落的能力和自我更新的能力。关于锂对神经发生影响的研究表明，锂可促进海马齿状回的干细胞增殖，并导致施旺氏细胞有丝分裂活性增强。锂被证实与神经保护和神经营养作用相关，具体作用反映在锂可改善突触的可塑性，促进细胞存活，抑制细胞凋亡等。在临床研究中发现，锂离子的治疗可增加大脑灰质的成分，尤其作用在额叶、海马和杏仁核等位置。锂对干细胞的作用涉及多条介质和信号通路，其中最重要的介质和信号通路被认为是糖原合成酶激酶-3（GSK-3）和Wnt/β-catenin通路，另外包括调节cAMP、蛋白激酶B、磷脂酰肌醇3-激酶（pi3k）和肌醇单磷酸酶（IMP）水平的信号通路等也与锂作用有紧密的联系。锂在现阶段被利用于治疗BD和降低痴呆症患病风险的临床实验中，并对神经退行性疾病发挥有益作用。除此之外，为了研究的发病机制和锂离子在其中的作用机制，从BD患者中获得的iPSCs也被广泛应用。

关键词: 锂, 造血干细胞, 神经干细胞, 诱导多能干细胞

Lithium has been used in modern psychiatry for more than 65 years, constituting a cornerstone of long-term treatment for bipolar disorder.A number of biological properties of lithium have been demonstrated, including its antiviral, blood and nervous system protective effects.The effects of lithium on hematopoiesis, mesenchymal, neural stem cells and induced pluripotent stem cells were reviewed. Since the 1970s, lithium's role in maintaining high levels of hematopoietic stem cells (HSCs) and growth factors has been reported. Lithium can improve homing ability, colony forming ability and self-renewal ability of hematopoietic stem cells. Studies on the effects of lithium on neurogenesis have shown that lithium can promote the proliferation of progenitor cells in the hippocampal dentate gyrus and lead to increased mitotic activity of schwann cells. Lithium has been proved to be associated with neuroprotection and neurotrophic effects, and its specific effects are reflected in its improvement of synaptic plasticity, promotion of cell survival and inhibition of apoptosis. In clinical studies, lithium ion therapy has been found to increase the components of gray matter in the brain, especially in the frontal lobe, hippocampus and amygdala. The effects of lithium on stem cells involve multiple mediators and signal pathways, among which the most important mediators and signal pathways are believed to be glycogen synthase kinase-3 (gsk-3) and Wnt/-catenin pathways. In addition, the regulation of cAMP, protein kinase B, phosphatidylinositol 3-kinase (pi3k) and inositol monophosphatase (IMP) levels are also closely related to the effects of lithium. Lithium is currently being used in clinical trials to treat bipolar disorder and reduce the risk of dementia, and has beneficial effects on neurodegenerative diseases. In addition, induced pluripotent stem cells obtained from patients with bipolar disorder have been widely used to study the pathogenesis and the mechanism of action of lithium.

Key words: Lithium, Hematopoietic stem cells, Neural stem cells, Induced pluripotent stem cell

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Research progress on the effect of lithium on hematopoietic stem cells and neural stem cells

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Research progress on the effect of lithium on hematopoietic stem cells and neural stem cells