【摘要】： 硒對人體是一個十分重要的微量元素[1],在人體中,其作用是廣譜的。它是多種酶的活動中心[2-10],在其人體生命活動中起到抵御疾病,防止衰老,增強(qiáng)機(jī)體免疫功能[11,12]。 硒在癌癥的化學(xué)預(yù)防和治療方面有明確的作用。然而,目前的研究資料顯示在其超營養(yǎng)水平和大劑量時才有明顯效果,這些劑量接近毒性水平。納米硒,采用最新納米技術(shù)制成的納米顆粒,其低毒高活性的特點(diǎn)能更多的釋放出硒防治癌癥的能量[13]。有關(guān)于硒功能研究的報道還有很多。然而,在硒對神經(jīng)系統(tǒng)調(diào)節(jié)作用的研究方面,我們還知之甚少。在其低毒性范圍內(nèi)防癌治癌的同時,是否會對人體神經(jīng)系統(tǒng)產(chǎn)生影響? 本文運(yùn)用膜片鉗技術(shù),首次以S-D大鼠背根神經(jīng)節(jié)細(xì)胞(DRG)為研究對象,在全細(xì)胞模式下,對不同濃度的亞硒酸鈉(Na2SeO3)和納米硒(Nano-Se)在細(xì)胞膜電流調(diào)節(jié)作用及其通道動力學(xué)方面進(jìn)行了較為深入的研究。其結(jié)果顯示:硒對細(xì)胞膜鉀電流無影響,然而,其對鈉電流的作用效果明顯。調(diào)節(jié)作用具有時間依賴性和濃度依賴性。在其營養(yǎng)性范圍內(nèi),電壓依賴型鈉電流增加;在弱毒性及毒性范圍內(nèi),鈉電流減少。近而,在對電壓依賴型鈉電流的分析中發(fā)現(xiàn),硒對TTX-R型鈉電流無影響,而對TTX-S型鈉電流有明顯的增強(qiáng)和抑制作用。在此前提下,進(jìn)一步較為詳細(xì)地研究了在低毒性范圍內(nèi)硒對電壓門控型TTX-S鈉通道電流的調(diào)節(jié)作用及相關(guān)動力學(xué)分析。通過對膜翻轉(zhuǎn)電位,膜電導(dǎo),穩(wěn)態(tài)失活,激活和恢復(fù)曲線及其相關(guān)參數(shù)的動力學(xué)分析,得出以下結(jié)論: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。硒的阻斷作用屬于通道-開放型阻斷,即在通道開放時才具有阻斷電流的作用。最后,通過在納米硒和亞硒酸鈉對比實(shí)驗(yàn)中的結(jié)果分析,我們提出以下結(jié)論及合理假設(shè):1)在保持高效生物活性的同時,納米硒具有比亞硒酸鈉更低的短期毒性,這一點(diǎn)能夠確保這種新型的納米藥物能在防癌抗癌的治療中得到廣泛應(yīng)用;2)納米硒和亞硒酸鈉作用于通道同一競爭位點(diǎn),先與結(jié)合位點(diǎn)結(jié)合的藥物使得后續(xù)藥物因無法與結(jié)合位點(diǎn)結(jié)合而失效;3)納米硒和亞硒酸鈉作用于通道內(nèi)不同的競爭位點(diǎn),先與對應(yīng)位點(diǎn)結(jié)合的藥物可使后加藥物的結(jié)合位點(diǎn)發(fā)生突變,致使后續(xù)藥物作用失效。
[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.
【學(xué)位授予單位】：華中科技大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2006
【分類號】：R341

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相關(guān)期刊論文 前4條

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