硒对细胞膜电流调控机制及通道动力学研究
发布时间：2018-07-24 15:05
【摘要】： 硒对人体是一个十分重要的微量元素[1],在人体中,其作用是广谱的。它是多种酶的活动中心[2-10],在其人体生命活动中起到抵御疾病,防止衰老,增强机体免疫功能[11,12]。 硒在癌症的化学预防和治疗方面有明确的作用。然而,目前的研究资料显示在其超营养水平和大剂量时才有明显效果,这些剂量接近毒性水平。纳米硒,采用最新纳米技术制成的纳米颗粒,其低毒高活性的特点能更多的释放出硒防治癌症的能量[13]。有关于硒功能研究的报道还有很多。然而,在硒对神经系统调节作用的研究方面,我们还知之甚少。在其低毒性范围内防癌治癌的同时,是否会对人体神经系统产生影响? 本文运用膜片钳技术,首次以S-D大鼠背根神经节细胞(DRG)为研究对象,在全细胞模式下,对不同浓度的亚硒酸钠(Na2SeO3)和纳米硒(Nano-Se)在细胞膜电流调节作用及其通道动力学方面进行了较为深入的研究。其结果显示:硒对细胞膜钾电流无影响,然而,其对钠电流的作用效果明显。调节作用具有时间依赖性和浓度依赖性。在其营养性范围内,电压依赖型钠电流增加;在弱毒性及毒性范围内,钠电流减少。近而,在对电压依赖型钠电流的分析中发现,硒对TTX-R型钠电流无影响,而对TTX-S型钠电流有明显的增强和抑制作用。在此前提下,进一步较为详细地研究了在低毒性范围内硒对电压门控型TTX-S钠通道电流的调节作用及相关动力学分析。通过对膜翻转电位,膜电导,稳态失活,激活和恢复曲线及其相关参数的动力学分析,得出以下结论:硒作用于通道孔洞,而非作用于通道蛋白外部表面附近或通道蛋白外部表面上。硒的阻断作用属于通道-开放型阻断,即在通道开放时才具有阻断电流的作用。最后,通过在纳米硒和亚硒酸钠对比实验中的结果分析,我们提出以下结论及合理假设:1)在保持高效生物活性的同时,纳米硒具有比亚硒酸钠更低的短期毒性,这一点能够确保这种新型的纳米药物能在防癌抗癌的治疗中得到广泛应用;2)纳米硒和亚硒酸钠作用于通道同一竞争位点,先与结合位点结合的药物使得后续药物因无法与结合位点结合而失效;3)纳米硒和亚硒酸钠作用于通道内不同的竞争位点,先与对应位点结合的药物可使后加药物的结合位点发生突变,致使后续药物作用失效。
[Abstract]:Selenium is a very important trace element in human body. It is the activity center of many enzymes [2-10], which can resist disease, prevent aging and enhance immune function in human life. Selenium has a definite role in the chemical prevention and treatment of cancer. However, current research data show that the effects are only apparent at their hypertrophic levels and high doses, which are close to toxic levels. Nano-selenium, which is made by the latest nano-technology, can release more energy of selenium to prevent and cure cancer [13] because of its low toxicity and high activity. There are many reports about the function of selenium. However, little is known about the role of selenium in regulating the nervous system. In its low toxic range of cancer prevention and treatment at the same time, whether the human nervous system will have an impact? Using patch-clamp technique, (DRG) of S-D rat dorsal root ganglion cells was first studied in the whole cell model. The effects of sodium selenite (Na2SeO3) and nano selenium (Nano-Se) on cell membrane current regulation and channel kinetics were studied. The results showed that selenium had no effect on potassium current of cell membrane, however, the effect of selenium on sodium current was obvious. The regulation is time dependent and concentration dependent. In the range of nutrition, the voltage-dependent sodium current increased, and the sodium current decreased in the weak toxicity and toxicity range. Recently, in the analysis of voltage-dependent sodium currents, it was found that selenium had no effect on TTX-R sodium currents, but significantly enhanced and inhibited TTX-S sodium currents. On this premise, the effect of selenium on the voltage-gated sodium channel current of TTX-S in the low toxicity range and the related kinetic analysis were studied in detail. Based on the kinetic analysis of membrane turnover potential, membrane conductance, steady-state inactivation, activation and recovery curves and related parameters, the following conclusions are drawn: selenium acts on channel holes, It does not act near the outer surface of the channel protein or on the external surface of the channel protein. The blocking effect of selenium belongs to channel-open blocking, that is, blocking current only when the channel is open. Finally, through the analysis of the results in the comparative experiments of nano selenium and sodium selenite, we put forward the following conclusions and reasonable assumptions: while maintaining high efficiency biological activity, nano selenium has lower short-term toxicity than sodium selenite. This ensures that this new nano-drug can be widely used in cancer prevention and anticancer therapy. (2) Nano-selenium and sodium selenite act on the same competitive site in the channel. The drug that binds to the binding site first causes the subsequent drug to fail because it cannot bind to the binding site. (3) Nano-selenium and sodium selenite act on different competitive sites in the channel. The drug that binds to the corresponding site can cause the mutation of the binding site of the additive drug, which results in the failure of the subsequent drug action.
【学位授予单位】：华中科技大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R341
本文编号：2141759
[Abstract]:Selenium is a very important trace element in human body. It is the activity center of many enzymes [2-10], which can resist disease, prevent aging and enhance immune function in human life. Selenium has a definite role in the chemical prevention and treatment of cancer. However, current research data show that the effects are only apparent at their hypertrophic levels and high doses, which are close to toxic levels. Nano-selenium, which is made by the latest nano-technology, can release more energy of selenium to prevent and cure cancer [13] because of its low toxicity and high activity. There are many reports about the function of selenium. However, little is known about the role of selenium in regulating the nervous system. In its low toxic range of cancer prevention and treatment at the same time, whether the human nervous system will have an impact? Using patch-clamp technique, (DRG) of S-D rat dorsal root ganglion cells was first studied in the whole cell model. The effects of sodium selenite (Na2SeO3) and nano selenium (Nano-Se) on cell membrane current regulation and channel kinetics were studied. The results showed that selenium had no effect on potassium current of cell membrane, however, the effect of selenium on sodium current was obvious. The regulation is time dependent and concentration dependent. In the range of nutrition, the voltage-dependent sodium current increased, and the sodium current decreased in the weak toxicity and toxicity range. Recently, in the analysis of voltage-dependent sodium currents, it was found that selenium had no effect on TTX-R sodium currents, but significantly enhanced and inhibited TTX-S sodium currents. On this premise, the effect of selenium on the voltage-gated sodium channel current of TTX-S in the low toxicity range and the related kinetic analysis were studied in detail. Based on the kinetic analysis of membrane turnover potential, membrane conductance, steady-state inactivation, activation and recovery curves and related parameters, the following conclusions are drawn: selenium acts on channel holes, It does not act near the outer surface of the channel protein or on the external surface of the channel protein. The blocking effect of selenium belongs to channel-open blocking, that is, blocking current only when the channel is open. Finally, through the analysis of the results in the comparative experiments of nano selenium and sodium selenite, we put forward the following conclusions and reasonable assumptions: while maintaining high efficiency biological activity, nano selenium has lower short-term toxicity than sodium selenite. This ensures that this new nano-drug can be widely used in cancer prevention and anticancer therapy. (2) Nano-selenium and sodium selenite act on the same competitive site in the channel. The drug that binds to the binding site first causes the subsequent drug to fail because it cannot bind to the binding site. (3) Nano-selenium and sodium selenite act on different competitive sites in the channel. The drug that binds to the corresponding site can cause the mutation of the binding site of the additive drug, which results in the failure of the subsequent drug action.
【学位授予单位】：华中科技大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R341
【参考文献】
相关期刊论文 前4条
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3 兰同汉,刘向明,顾正,林家瑞;离子通道门控机制研究进展[J];生物医学工程学杂志;2002年02期
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