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内源性阿片样物质吗啡能否抑制神经干细胞增殖?

Could the endogenous opioid, morphine, prevent neural stem cell proliferation?

机构信息

Research Center for Science and Technology in Medicine, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Med Hypotheses. 2011 Feb;76(2):225-9. doi: 10.1016/j.mehy.2010.10.002. Epub 2010 Nov 3.

Abstract

In spite of widespread use of morphine to treat pain in patients, little is known about the effects of this opioid on many cells including stem cells. Moreover the studies have been shown controversial results about morphine effects on several kinds of cells. It is well-known that morphine exposure could decrease testosterone levels in brain and spinal cord. Morphine could increase the activity of 5α-redutase, the enzyme that converts testosterone into its respective 5α-redutase derivative dihydrotestosterone (DHT). Also it could increase aromatase activity that converts testosterone to estradiol. Proliferation of neural stem cells was observed in human stem cells after exposure to certain combinations of steroids especially testosterone. On the other hand DHT has negative effect in neural stem cell reproduction. Morphine induces over-expression of p53 gene that could mediate stem cell apoptosis. Therefore we hypothesized that due to reduction in the testosterone levels, elevation in the DHT levels, and over-expression of p53 gene, morphine could prevent neural stem cell proliferation.

摘要

尽管吗啡被广泛用于治疗患者的疼痛,但人们对这种阿片类药物对包括干细胞在内的许多细胞的影响知之甚少。此外,关于吗啡对几种细胞的影响的研究结果存在争议。众所周知,吗啡暴露会降低大脑和脊髓中的睾丸激素水平。吗啡可以增加 5α-还原酶的活性,这种酶将睾丸激素转化为相应的 5α-还原酶衍生物二氢睾丸激素(DHT)。它还可以增加芳香酶的活性,将睾丸激素转化为雌二醇。暴露于某些类固醇(尤其是睾丸激素)组合后,在人类干细胞中观察到神经干细胞的增殖。另一方面,DHT 对神经干细胞的繁殖有负面影响。吗啡诱导 p53 基因的过度表达,从而介导干细胞凋亡。因此,我们假设由于睾丸激素水平降低、DHT 水平升高以及 p53 基因过度表达,吗啡可能会阻止神经干细胞的增殖。

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