CN114917369A - 黄连素在荧光手术导航中的应用 - Google Patents
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Abstract
本发明公开了黄连素在荧光手术导航中的应用,通过利用黄连素在紫外光激发下发出可见光荧光的特性,用于引导小鼠、大鼠和兔子三种实验动物的腋窝淋巴结切除手术,在手术中,含有黄连素的淋巴结在紫外灯照射下发出明亮的黄色荧光。根据该荧光的引导,可完成包含淋巴结的精准切除在内的各类手术导航。黄连素作为一种已被临床应用的天然药物,安全性已得到充分的验证,因此本发明为临床上荧光手术导航提供了一种新的荧光材料。
Description
技术领域
本发明涉及黄连素的一种新用途,具体地说,涉及黄连素在荧光手术导航中的应用。
背景技术
近年来,癌症逐渐成为威胁人类健康的大敌。外科手术切除是癌症最主要的治疗方法。虽然术前CT、磁共振成像及正电子发射计算机断层扫描等影像技术对病灶评估起重要作用,但由于时空差异性以及术中解剖与术前图像存在显著的差异,目前外科医师在术中探测和切除肿瘤仍主要凭借其经验,利用触诊和肉眼视觉完成病灶的识别与切除。随着医学影像学的发展,术中影像导航技术得到长足的发展。术中影像导航,是利用光学分子自身的荧光特性,术前或术中注射荧光探针后,在光学分子影像系统的特定激发波下,荧光探针发射相应的波长,被荧光成像系统设备所接收,在显示屏上清晰显示出所需要标记的器官或组织的形态,例如胆管、输尿管、淋巴结、神经等,从而引导手术。
在针对于癌症的手术中,大多都需要清扫淋巴结以阻断癌细胞可能存在的远处转移,对淋巴结清扫的不彻底将严重影响患者的预后水平。然而,在实际手术过程中,各种解剖结构错综复杂,加之人体内解剖学变异较多,较难分辨淋巴结与周围组织。为了解决淋巴结显像问题,已经开发了放射性示踪剂、发色团等示踪剂,但是它们存在辐射大、检出率低等不足。所以,能够对淋巴结进行示踪的荧光探针逐渐受到外科医生的重视。
黄连素(盐酸小檗碱,berberine),是一种从许多草本植物,如黄连、黄柏中分离的异喹啉生物碱,具有对抗多种病原微生物的作用,临床上常用于治疗细菌性痢疾、肠胃炎等疾病。近年来,有学者提到它是一种天然的聚集诱导发光分子(AIEgen)。然而,利用它的可见光荧光进行手术导航的应用几乎没有被报道过,具有广阔的应用前景。
发明内容
本发明目的在于针对现有技术的不足,提出一种黄连素的新用途,为实现荧光导航手术提供一种新的荧光材料。
本发明的目的是通过以下技术方案来实现的:本发明提供了一种黄连素在荧光手术导航中的应用。
进一步地,所述的黄连素使用β-环糊精或它的衍生物包裹,增加紫外激发的荧光亮度和水溶性。
进一步地,所述的β-环糊精或它的衍生物与黄连素的摩尔比为1:1。
进一步地,所述的β-环糊精或它的衍生物包裹黄连素的反应过程使用乙醇助溶,在65℃下反应24小时。
进一步地,荧光手术导航过程中利用紫外灯作为激发光源。
进一步地,所述荧光手术是淋巴结切除术。
进一步地,所述淋巴结在紫外灯照射下发出可见光波段的明亮黄色荧光,为荧光手术提供引导。
本发明的有益效果:
1、提供了黄连素应用于荧光手术导航。本发明使用β-环糊精(及其衍生物)包裹黄连素,增加了黄连素在水中的溶解度和紫外灯激发下的荧光强度。
2、提供了黄连素在手术中精准显示淋巴结的应用例,通过小鼠、大鼠和兔子的动物模型验证,在紫外灯激发下,淋巴结的可见荧光引导淋巴结的精准切除,为荧光导航手术提供了一种新的荧光材料。
附图说明
为了使本发明的目的、技术方案、效果更加清楚,本发明提供以下附图:
图1同浓度黄连素与β-环糊精包裹的黄连素的荧光光谱;
图2紫外灯的发射谱;
图3黄连素精准导航小鼠腋窝淋巴结切除术;
图4黄连素精准导航大鼠腋窝淋巴结切除术;
图5黄连素精准导航兔子腋窝淋巴结切除术。
具体实施方式
下面对本发明提供的具体实施方式作详细说明。显然,所描述的实施例仅仅是本发明一部分实施例,而不是全部的实施例,基于本发明中的实施例,本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例,都属于本发明保护的范围。
1、材料和方法
1.1实验材料
黄连素(Berberine)、β-环糊精购自阿拉丁,实验动物小鼠、大鼠和兔子来自浙江大学附属邵逸夫医院,饲养条件为:温度:24-26℃、相对湿度:40-60%。室内采用人工照明,自由采食,饲料和水均经过高温消毒处理。
1.2β-环糊精包裹黄连素
取200mgβ-环糊精,溶解在20-30ml的混合溶剂(EtOH:H2O体积比=1:1)中;另取59mg盐酸小檗碱(黄连素)溶解在10ml的混合溶剂中。将两种溶液倒入同一烧杯中,65℃下反应24h,随后在旋转蒸发仪中蒸发掉部分溶剂,冻干,即可得到黄色固体粉末状的β-环糊精包裹的盐酸小檗碱。将1mg盐酸小檗碱和1mgβ-环糊精包裹的盐酸小檗碱分别溶于水中,测荧光光谱,发现β-环糊精包裹的盐酸小檗碱亮度有显著提升,如图1所示。
1.3手术操作
术前准备:首先用质量分数为1%的戊巴比妥将动物麻醉,利用胶带将其固定在放有聚乙烯黑色避光纸的台面上。利用剃毛器将局部术野剃毛显露,用碘伏涂抹皮肤消毒三遍。向掌垫注射浓度为1mg/ml的β-环糊精包裹的黄连素溶液100μL,等待10分钟后,开始手术。
术中操作:根据实验动物的不同在一侧腋窝附近处开不同大小的切口,小鼠切口约为1cm,大鼠切口约为1.5cm,兔切口约为2cm。用镊子与血管钳钝性分离腋窝部脂肪组织,打开紫外灯照射术野,紫外灯的发射光谱如图2所示。实验中,可用肉眼观察到含有黄连素的小鼠淋巴结(图3),大鼠淋巴结(图4)和兔淋巴结(图5)在紫外灯激发下发出的明黄色荧光,根据荧光,可完成淋巴结的识别,三种实验动物的淋巴结边缘清晰,包膜完整,切除过程顺利。切下的淋巴结在紫外光激发下仍有明显的明黄色荧光。
上述实施例用来解释说明本发明,而不是对本发明进行限制,在本发明的精神和权利要求的保护范围内,对本发明作出的任何修改和改变,都落入本发明的保护范围。
Claims (7)
1.一种黄连素在荧光手术导航中的应用。
2.根据权利要求1所述的应用,其特征在于,所述的黄连素使用β-环糊精或它的衍生物包裹,增加紫外激发的荧光亮度和水溶性。
3.根据权利要求2所述的应用,其特征在于,所述的β-环糊精或它的衍生物与黄连素的摩尔比为1:1。
4.根据权利要求2所述的应用,其特征在于,所述的β-环糊精或它的衍生物包裹黄连素的反应过程使用乙醇助溶,在65℃下反应24小时。
5.根据权利要求1所述的应用,其特征在于,荧光手术导航过程中利用紫外灯作为激发光源。
6.根据权利要求1所述的应用,其特征在于,所述荧光手术是淋巴结切除术。
7.根据权利要求6所述的应用,其特征在于,所述淋巴结在紫外灯照射下发出明亮黄色荧光,为荧光手术提供引导。
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