本文選題：敬釗纓毛蛛粗毒 + 新生大鼠心室肌細胞(NRVMs)��； 參考：《湖南師范大學》2015年碩士論文

【摘要】：心血管疾病對人們健康的威脅日趨嚴重與明顯,被喻為“三大殺手”之一。大量的研究已經證明了心臟離子通道的電生理特性直接影響著心肌細胞的靜息電位以及心臟動作電位的形狀和時長。因此,我們通過利用不同的檢測方法來試圖探討敬釗纓毛蛛粗毒與心臟離子通道相互作用的電生理特點,從而為挖掘找到潛在的作用靶點或尋找工具分子奠定基礎。敬釗纓毛蛛(Chilobrachys jingzhao)是發(fā)現(xiàn)于我國海南地區(qū)的一種有毒蜘蛛,從該種蜘蛛毒腺中獲取的粗毒具有大量的毒素肽物質,就好比一個豐富的毒素肽庫。然而,目前關于敬釗粗毒對心臟離子通道影響的研究少之又少。本文,旨在初步探究敬釗粗毒--這個充滿潛力的毒素庫--中是否也存在有望成為治療心臟疾病的藥用成分,所以首先利用敬釗粗毒來初步探究其對新生大鼠心室肌(neonatal rat ventricular myocytes(NRVMs))相關電生理的影響關系。為此,在這項研究中我利用了全細胞膜片鉗技術并通過三個不同的方面開展研究:1,檢測敬釗粗毒對新生大鼠心室肌細胞的動作電位的影響;2,檢測敬釗粗毒對新生大鼠心室肌細胞的全電流;3,進一步分別檢測敬釗粗毒對新生大鼠心室肌細胞上各種電流,即鈉電流(INa)、內向整流鉀電流(IK1)、快激活延遲整流鉀電流(IKr)、瞬時外向鉀電流(Ito1)、慢激活延遲整流鉀電流(IKs)、鈣電流等單獨存在時的作用。我們發(fā)現(xiàn),100μg/m L敬釗粗毒對ICaL的增強作用明顯,增加幅度為132±4.0%,而對INa抑制了96.7±3.4%,對IKr的峰電流、尾電流以及IKr去極化末部的電流、的抑制分別為54.3±3.2%、60.8±4.3%和35.3±5.3%。另外,該粗毒對IKs,Ito1和IK1電流沒有明顯的影響,并且這些分別檢測的離子電流數(shù)據與檢測全電流得到的實驗結果是吻合的,這表明敬釗粗毒對新生大鼠心室肌離子通道作用具有復雜性,表現(xiàn)出一個多方面的藥理作用。此外,通過敬釗粗毒對NRVMs的動作電位有微弱的延長作用并且這種延長作用與動作電位的刺激頻率有關聯(lián)。綜上可知,敬釗粗毒對NRVMs上的多種離子通道的電生理特性有影響,具有成為研發(fā)治療心臟疾病藥用分子的潛力。
[Abstract]:Cardiovascular disease is becoming more and more serious and obvious to people's health, and it is regarded as one of the "three killers". A large number of studies have proved that the electrophysiological characteristics of cardiac ion channels directly affect the resting potential of cardiac cells and the shape and duration of cardiac action potential. Therefore, we try to explore the electrophysiological characteristics of the interaction between the crude venom of Spider Jingzhao and the ion channel of the heart by using different detection methods, so as to lay a foundation for finding potential targets or searching for tool molecules. Chilobrachys jingzhao is a poisonous spider found in Hainan area of China. The crude toxin obtained from the venomous gland of the spider has a large amount of toxin peptides, which is like a rich toxin peptide library. However, there are few studies on the effect of Jingzhao crude toxin on cardiac ion channels. The purpose of this paper is to preliminarily explore whether there is also a medicinal component in Jingzhao crude toxin, which is a potential toxin pool, that could be used to treat heart disease. Therefore, the effects of Jingzhao crude toxin on (neonatal rat ventricular myocytes (NRVMs in neonatal rat ventricular muscle were studied. To this end, In this study, I made use of whole-cell patch clamp technique and carried out a study on the effect of Jingzhao crude toxin on the action potential of ventricular myocytes in neonatal rats by using three different aspects, I. e., the effects of Jingzhao crude toxin on the heart of newborn rats and the effects of Jingzhao crude toxin on the heart of newborn rats. The total current of ventricular myocytes (VMC) was measured respectively to detect the various currents of Jingzhao crude toxin on ventricular myocytes of newborn rats. Such as sodium current (Ina), inward rectifier potassium current (IK1), fast activated delayed rectifier potassium current (IKr), transient outward potassium current (Ito1), slow activation delayed rectifier potassium current (IKs), calcium current and so on. We found that 100 渭 g / mL Jingzhao crude toxin enhanced ICaL obviously by 132 鹵4.0, but inhibited 96.7 鹵3.4 of INa, 54.3 鹵3.2% of peak current and tail current of IKr and 35.3 鹵5.3 鹵5.3of the end of depolarization of IKr, respectively. In addition, the crude poison has no obvious effect on the Ito1 and IK1 currents, and these ion current data measured by the two methods are in agreement with the experimental results obtained from the detection of the full current. This indicates that Jingzhao crude toxin has a complex effect on the ion channel in neonatal rat ventricular myocytes, and it shows a variety of pharmacological effects. In addition, the action potential of NRVMs was slightly prolonged by Jingzhao crude toxin, and the prolongation was related to the stimulation frequency of action potential. It can be concluded that Jingzhao crude toxin has an effect on the electrophysiological characteristics of various ion channels on NRVMs and has the potential to be a medicinal molecule for the treatment of heart disease.
【學位授予單位】：湖南師范大學
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：R54

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