CN108489941B - 溴酚蓝在作为检测牛胰岛素淀粉样纤维探针和作为牛胰岛素淀粉样纤维抑制剂方面的应用 - Google Patents
溴酚蓝在作为检测牛胰岛素淀粉样纤维探针和作为牛胰岛素淀粉样纤维抑制剂方面的应用 Download PDFInfo
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Abstract
溴酚蓝在作为检测牛胰岛素淀粉样纤维探针和作为牛胰岛素淀粉样纤维抑制剂方面的应用，属于生物医学技术领域。荧光光谱图显示溴酚蓝加到牛胰岛素淀粉样纤维溶液后，荧光强度是牛胰岛素溶液与溴酚蓝混合后的三倍多，由于溴酚蓝与牛胰岛素和牛胰岛素淀粉样纤维结合后荧光强度的明显差异性，表明溴酚蓝可以作为探针准确检测牛胰岛素淀粉样纤维。用溴酚蓝追踪监测牛胰岛素淀粉样纤维的形成过程，第一阶段荧光强度变化较为缓慢，第二阶段荧光强度迅速增强，第三阶段荧光强度变为较为平稳。在制备牛胰岛素淀粉样的过程中，加入溴酚蓝后，圆二色谱图显示牛胰岛素的二级结构没有出现应该有的变化，即溴酚蓝的加入成功抑制了牛胰岛素淀粉样纤维的形成。
Description
技术领域
本发明属于生物医学技术领域，特别是涉及溴酚蓝在作为检测牛胰岛素淀粉样纤维探针和作为牛胰岛素淀粉样纤维抑制剂方面的应用。
背景技术
蛋白的错误折叠导致的淀粉样纤维生成是诱发很多相关疾病的关键因素。长久以来，淀粉样纤维的研究是近年来在化学、生物学、医学方面的重要课题。越来越多的研究主要是因为淀粉样纤维的产生与许多疾病直接相关，有关报道指出大概有几十种疾病是因为形成淀粉样纤维引起的，例如：阿尔兹海默症，帕金和亨廷顿病,海绵状脑病，II型糖尿病，心率不齐，类风湿性关节炎，动脉粥样硬化，催乳素瘤，多神经病等等。因此，对淀粉样纤维的识别以及抑制的研究在推动发展淀粉样纤维形成的机理和促进发展医学诊断救治的手段上有着重要的意义。
发明内容
溴酚蓝的结构式如下所示，溴酚蓝可以特异性识别牛胰岛素淀粉样纤维。在作为检测牛胰岛素淀粉样纤维探针和作为牛胰岛素淀粉样纤维抑制剂方面得到应用。
附图说明
图1：在牛胰岛素溶液(曲线1)与牛胰岛素淀粉样纤维溶液(曲线2)中分别加入溴酚蓝水溶液的荧光光谱图；
图2：利用溴酚蓝监测牛胰岛素淀粉样纤维形成过程的相对荧光强度曲线图； I0为溴酚蓝水溶液的荧光强度，I为将溴酚蓝水溶液加入牛胰岛素后溶液的荧光强度。
图3：不加入溴酚蓝的溶液，牛胰岛素在25mM、NaCl/HCl(pH＝1.6),65℃条件下孵育0min和600min的圆二色谱图(纵坐标表示椭圆率，横坐标表示波长)；
图4：加入溴酚蓝的溶液，牛胰岛素在25mM、NaCl/HCl(pH＝1.6),65℃条件下孵育0min和600min的圆二色谱图(纵坐标表示椭圆率，横坐标表示波长。仪器：圆二色谱仪)。
具体实施方式
实施例1：
PBS缓冲液配方：19mL、0.2M NaH2PO4水溶液和81mL、0.2M Na2HPO4水溶液的混合。配制1mM溴酚蓝水溶液，取0.02mL溴酚蓝水溶液分别加入到0.01mL、2.5mM牛胰岛素的PBS缓冲液溶液(牛胰岛素在PBS缓冲液中可以稳定存在，不会生成淀粉样纤维)中和0.01mL、2.5mM牛胰岛素淀粉样纤维 NaCl/HCl溶液中(用HCl调节NaCl水溶液的pH＝1.6，然后将牛胰岛素加入到 NaCl水溶液中，牛胰岛素的浓度为2.5mM，在65℃条件下孵育3小时，得到牛胰岛素淀粉样纤维溶液；NaCl水溶液中NaCl的浓度是25mM)，再加入0.97mL PBS缓冲液稀释，将上述溶液放到荧光光谱仪中测试其荧光强度。荧光光谱图显示溴酚蓝加到牛胰岛素淀粉样纤维溶液后，荧光强度是牛胰岛素溶液与溴酚蓝混合后的三倍多，如图1。由于溴酚蓝与牛胰岛素和牛胰岛素淀粉样纤维结合后荧光强度的明显差异性，表明溴酚蓝可以作为探针准确检测牛胰岛素淀粉样纤维。
实施例2：
溴酚蓝可以监测牛胰岛素淀粉样纤维的形成过程。许多与淀粉样纤维相关的疾病的发病机理尚不清楚，因此对于淀粉样纤维的形成过程的监测将为探索淀粉样纤维相关疾病的发病机理提供了一个思路。牛胰岛素在pH＝1.6、25mM NaCl/HCl溶液(用HCl调节NaCl水溶液的pH＝1.6，NaCl水溶液中NaCl的浓度是25mM)、65℃条件下孵育，可以生成胰岛素淀粉样纤维。将牛胰岛素溶解在pH＝1.6、25mM NaCl/HCl溶液中(牛胰岛素的浓度为2.5mM)，置于65℃下，在不同时间点取0.01mL、2.5mM上述溶液，然后向其中加入0.02mL、1mM 溴酚蓝水溶液，再加入0.97mL PBS缓冲液，将上述溶液放到荧光光谱仪中测试其荧光强度。随着牛胰岛素淀粉样纤维的形成，荧光强度会有明显变化。如图2 所示(对应曲线2，0μM表示在生成胰岛素淀粉样纤维的过程中，不加入溴酚蓝溶液(抑制剂))，利用溴酚蓝追踪监测牛胰岛素淀粉样纤维的形成过程，可将其分为三个阶段，第一阶段(0～130min)荧光强度变化较为缓慢，第二阶段 (130～250min)荧光强度迅速增强，第三阶段(250～600min)荧光强度变为较为平稳。
实施例3：
溴酚蓝可以作为牛胰岛素淀粉样纤维的抑制剂。使牛胰岛素溶解在pH＝1.6、25mM NaCl/HCl溶液中，置于65℃下开始孵育，牛胰岛素浓度为2.5mM。取 0.9mL的上述牛胰岛素溶液，再加入1mM、0.1mL溴酚蓝水溶液，在不同时间点取0.01mL、2.5mM上述溶液，然后向其中加入1mM、0.02mL溴酚蓝水溶液，再加入0.97mL PBS缓冲液，将上述溶液放到荧光光谱仪中测试其荧光强度。发现荧光强度基本没有变化，即牛胰岛素淀粉样纤维形成受阻(对应图2中的曲线1，因为牛胰岛素与溴酚蓝(抑制剂)一起孵育，检测时再加入溴酚蓝(探针)，结果显示荧光强度没有变化，与图1的结果吻合)。
将牛胰岛素溶解在pH＝1.6、25mM NaCl/HCl溶液中，置于65℃下孵育，牛胰岛素浓度为2.5mM。分别取两份0.9mL的上述牛胰岛素溶液，然后，一份加入1mM、0.1mL溴酚蓝水溶液，另一份加入0.1mL的超纯水。
对于不加入溴酚蓝的溶液，分别在0min和600min取上述溶液，装在0.5mm 的比色皿中，设置光谱在190～260nm的波长范围内扫描，数据间距0.1nm，带宽1nm，扫描速度为50nm min-1。采集三次扫描并取平均值，并减去溶剂的CD 信号。得到了相应的圆二色谱图(曲线1对应于孵育0min，曲线2对应于孵育 600min)。如图3所示，牛胰岛素中没有加入溴酚蓝，形成淀粉样纤维后二级结构发生了明显的变化(如图所示，二级结构发生变化，曲线由折线变为平滑)。
对于加入溴酚蓝的溶液，分别在0min和600min取上述溶液，装在0.5mm 的比色皿中，设置光谱在190～260nm的波长范围内扫描，数据间距0.1nm，带宽1nm，扫描速度为50nmmin-1。采集三次扫描并取平均值，并减去溶剂的CD 信号。得到了相应的圆二色谱图(曲线1对应于孵育0min，曲线2对应于孵育 600min)。如图4所示，在加入溴酚蓝后，牛胰岛素的二级结构没有出现应该有的结构变化，即溴酚蓝的加入成功抑制了牛胰岛素淀粉样纤维的形成。
Claims (2)
1.溴酚蓝在作为检测牛胰岛素淀粉样纤维探针方面的应用，具体包括以下步骤：PBS缓冲液配方：19mL、0.2M NaH2PO4水溶液和81mL、0.2M Na2HPO4水溶液的混合；配制1mM溴酚蓝水溶液，取0.02mL溴酚蓝水溶液分别加入到0.01mL、2.5mM牛胰岛素的PBS缓冲液溶液中和0.01mL、2.5mM牛胰岛素淀粉样纤维NaCl/HCl溶液中，其中，用HCl调节NaCl水溶液的pH＝1.6，然后将牛胰岛素加入到NaCl水溶液中，牛胰岛素的浓度为2.5mM，在65°C条件下孵育3小时，得到牛胰岛素淀粉样纤维溶液；NaCl水溶液中NaCl的浓度是25mM，再加入0.97mLPBS缓冲液稀释，将上述溶液放到荧光光谱仪中测试其荧光强度。
2.溴酚蓝在作为牛胰岛素淀粉样纤维抑制剂方面的应用，具体包括以下步骤：牛胰岛素溶解在pH＝1 .6、25mM NaCl/HCl溶液中，置于65°C下开始孵育，牛胰岛素浓度为2.5mM；取0.9mL的上述牛胰岛素溶液，再加入1mM、0.1mL溴酚蓝水溶液，在不同时间点取0.01mL、2.5mM上述溶液，然后向其中加入1mM、0.02mL溴酚蓝水溶液，再加入0.97mLPBS缓冲液，将上述溶液放到荧光光谱仪中测试其荧光强度。
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| CN112525868B (zh) * | 2019-09-19 | 2022-04-22 | 吉林大学 | 喹哪啶红及其衍生物在制备检测淀粉样纤维的试剂盒中的应用 |
| CN111751415B (zh) * | 2020-06-15 | 2022-08-12 | 华南师范大学 | 一种胰岛素淀粉样纤维化的电化学检测方法 |
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