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睫状神经营养因子的全身给药可诱导啮齿动物恶病质。

Systemic administration of ciliary neurotrophic factor induces cachexia in rodents.

作者信息

Henderson J T, Seniuk N A, Richardson P M, Gauldie J, Roder J C

机构信息

Samuel Lunenfeld Research Institute, Division of Neurobiology and Molecular Immunology, Mount Sinai Hospital, Toronto, Ontario, Canada.

出版信息

J Clin Invest. 1994 Jun;93(6):2632-8. doi: 10.1172/JCI117276.

DOI:10.1172/JCI117276
PMID:8201002
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC294503/
Abstract

Ciliary neurotrophic factor (CNTF) has previously been shown to promote the survival of several classes of neurons and glial. We report here that in addition to its effects on the nervous system, CNTF can induce potent effects in extra-neural tissues. Implantation of C6 glioma cells engineered to secrete CNTF either subcutaneously or into the peritoneal cavity of adult mice, or systemic injections of purified rat or human recombinant CNTF, resulted in a rapid syndrome of weight loss resulting in death over a period of 7-10 d. This weight loss could not be explained by a reduction in food intake and involved losses of both fat and skeletal muscle. CNTF also induced the synthesis of acute phase proteins such as haptoglobin. Implantation of C6 lines expressing a nonsecreted form of CNTF, or the parental C6 line itself, did not result in wasting effects. Analysis of this CNTF-induced wasting indicates similarities with the previously described cachectins, tumor necrosis factor, interleukin 6, and leukemia inhibitory factor, but does not involve the induction of these cytokines.

摘要

睫状神经营养因子(CNTF)此前已被证明可促进几类神经元和神经胶质细胞的存活。我们在此报告,除了对神经系统有作用外,CNTF还能在神经外组织中诱导显著效应。将经基因工程改造可分泌CNTF的C6胶质瘤细胞皮下植入成年小鼠或注入成年小鼠腹腔,或全身注射纯化的大鼠或人重组CNTF,会导致迅速的体重减轻综合征,在7至10天内导致死亡。这种体重减轻不能用食物摄入量减少来解释,涉及脂肪和骨骼肌的损失。CNTF还诱导了急性期蛋白如触珠蛋白的合成。植入表达非分泌形式CNTF的C6细胞系或亲本C6细胞系本身,不会导致消瘦效应。对这种由CNTF诱导的消瘦的分析表明,它与先前描述的恶病质素、肿瘤坏死因子、白细胞介素6和白血病抑制因子有相似之处,但不涉及这些细胞因子的诱导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6319/294503/60fbdb3c94a7/jcinvest00035-0342-e.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6319/294503/d131ae41e0fc/jcinvest00035-0342-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6319/294503/b568fa26d192/jcinvest00035-0342-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6319/294503/fdc4904d9990/jcinvest00035-0342-c.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6319/294503/00719262131d/jcinvest00035-0342-d.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6319/294503/60fbdb3c94a7/jcinvest00035-0342-e.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6319/294503/d131ae41e0fc/jcinvest00035-0342-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6319/294503/b568fa26d192/jcinvest00035-0342-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6319/294503/fdc4904d9990/jcinvest00035-0342-c.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6319/294503/00719262131d/jcinvest00035-0342-d.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6319/294503/60fbdb3c94a7/jcinvest00035-0342-e.jpg

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本文引用的文献

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Ciliary neurotrophic factor prevents retrograde neuronal death in the adult central nervous system.睫状神经营养因子可预防成体中枢神经系统中的逆行性神经元死亡。
Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2222-6. doi: 10.1073/pnas.90.6.2222.
2
CNTF protection of oligodendrocytes against natural and tumor necrosis factor-induced death.睫状神经营养因子对少突胶质细胞的保护作用:抵抗自然因素及肿瘤坏死因子诱导的死亡
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Cross-linking identifies leukemia inhibitory factor-binding protein as a ciliary neurotrophic factor receptor component.
白血病抑制因子在围产期缺氧缺血性脑损伤中的神经再生和保护作用。
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The Etiology and Impact of Muscle Wasting in Metastatic Cancer.转移性癌症中肌肉减少症的病因和影响。
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Small RNAome profiling from human skeletal muscle: novel miRNAs and their targets associated with cancer cachexia.来自人类骨骼肌的小RNA组分析:与癌症恶病质相关的新型微小RNA及其靶标
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A combination of cytokines EGF and CNTF protects the functional beta cell mass in mice with short-term hyperglycaemia.细胞因子表皮生长因子(EGF)和睫状神经营养因子(CNTF)联合使用可保护短期高血糖小鼠的功能性β细胞群。
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Understanding cachexia as a cancer metabolism syndrome.将恶病质理解为一种癌症代谢综合征。
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Fatal syndrome in mice engrafted with cells producing high levels of the leukemia inhibitory factor.
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Human hepatocyte-stimulating factor-III and interleukin-6 are structurally and immunologically distinct but regulate the production of the same acute phase plasma proteins.
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