CN102579418A - 三七素在制备治疗神经变性病药物中的应用 - Google Patents
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Abstract
本发明涉及的是三七素的药物应用。具体的，本发明涉及的是小剂量三七素作为制备治疗慢性神经疾病的药物中的应用。本实验的研究人员采用细胞学方法，通过建立细胞慢性缺氧模型等，采用细胞形态观察、细胞染色等方法证实，小剂量的三七素可对慢性缺氧作用引起的神经源性细胞损伤具有保护作用，提示小剂量三七素对慢性神经疾病有保护作用。
Description
技术领域
本发明涉及三七素的一种新用途，具体涉及三七素在制备治疗神经变性病药物中的用途，属于医药领域。
背景技术
神经变性病 (Neurodegenerative Diseases) 是指由于神经元变性、凋亡所导致的神经系统退行性疾病。组织病理学研究均显示神经元缓慢渐进性凋亡，大多在神经细胞内存在蛋白质的异常聚集，形成包涵体，提示它们可能具有相似的发病机制，如基因突变线粒体功能异常、自由基产生、兴奋性毒性、蛋白转录后修饰异常、神经营养因子缺乏等，但具体病因不明。临床表现主要分为两种：运动功能障碍和记忆与认知功能障碍。这类疾病临床多隐袭起病，病程缓慢进展，可持续多年甚至十几年或更长，部分病例可有家族遗传史。治疗尚无成熟有效的方法，部分症状（如帕金森病的症状）可因有经验的治疗而缓解，但总体病程不断进展。所以切实找到一种可行的办法对该类疾病进行早期干预、早期治疗是需要积极解决的问题。
三七素是1981年日本科学家从三七中发现了具有止血活性的成分，其结构式如下： 
，命名为三七素。它其实是一种特殊的氨基酸，人参属的几种重要中药均含有止血成分三七素，但以三七中含量最高（0.90%），人参次之(0.50%)，西洋参最低（0.31%）。 三七素可通过缩短凝血时间、凝血酶原时间等发挥止血作用。另外，许多研究发现三七素具有神经毒作用。文献报道，三七素静脉注射大鼠50mg/kg（有效治疗剂量）下神经毒性反应不明显，高剂量（8-12倍有效治疗剂量）可能产生神经毒性。高浓度三七素（10mM）抑制神经元细胞的增殖活动。三七素的神经毒性是由于其促进谷氨酸释放使兴奋性氨基酸受体过度兴奋引起。然而发明人实验发现持续给予小剂量的三七素（0.01mM）对细胞不仅没有损伤作用，还会进一步促进细胞增殖，提示其具有细胞保护作用。
发明内容
本发明的目的在于提供三七素在制备神经变性病药物中的新用途。
有效成分含有三七素的药物可采用片剂、胶囊剂、散剂、丸剂、颗粒剂、注射剂或乳剂。上述制剂中可含有辅助物质、稳定剂、润湿剂和其它常用的添加剂，如乳糖、柠檬酸、酒石酸、硬脂酸镁、石膏粉、蔗糖、玉米淀粉、滑石粉、明胶、琼脂、果胶、花生油、橄榄油、可可脂、乙二醇、抗坏血酸、甘露醇等。
上述的制剂可按照各种制剂常规的制备工艺制成。
附图说明
图1 不同浓度三七素作用后的PC12细胞图片；
图2 实验各组的细胞染色图片；
图3染色实验统计图，*P<0.05 慢性缺氧组与正常对照组相比；#P<0.05 三七素干预组与慢性缺氧组相比。
具体实施方式
细胞实验
1 材料与方法
1.1 细胞培养与分组
本实验采用神经细胞株PC12细胞（第四军医大学西京医院提供），培养于含体积分数10%胎牛血清的DMEM培养基中，37℃、5% CO 条件下培养，1:4传代，选取对数生长期细胞进行实验。
形态学观察
细胞按5×104/孔密度接种于24孔板，培养48小时后各孔分别加入不同浓度的三七素，再培养48小时后显微镜下采图，观察细胞形态变化。
慢性缺氧模型的建立
实验共分三组，分别为正常对照组、慢性缺氧组、慢性缺氧三七素干预组（根据上步形态学观察实验筛选出三七素实验用浓度0.01mM）。将细胞接种于30mm培养皿中（5×104/皿），置37℃、5%CO2培养箱中培养48小时；用无血清培养液洗涤细胞两次，再加三七素（含1%血清培养液80μl+药物20μl）；药物作用48小时后参照Raquel等人的方法建立慢性缺氧模型。将实验室用慢性缺氧组与慢性缺氧三七素干预组细胞置入事先准备好的湿盒中，向盒中通入氮气，观察氧气含量表，至8%氧气含量时停止通入氮气，再将湿盒放入细胞孵箱中，培养过夜，12小时候取出染色。
Hoechst33342/PI双重染色对比细胞受损伤情况
处理好的PC12细胞用0.01MPBS液洗一遍，每皿中加入配好的Hoechst33342/PI染料（Hoechst33342比例1:5000；PI1μg·ml）1ml,室温避光30分钟，置显微镜下采图。红色荧光标记细胞为死亡细胞，蓝色荧光标记所有细胞（存活及死亡细胞）。
统计学方法
多组间比较用单因素方差分析，用SPSS13. 0统计软件包进行数据处理，P < 0.05为差异有显著性。
结果
2.1细胞形态观察
如图1所示，三七素药物作用两天后可见，药物浓度0.05mM至0.5mM作用后的细胞形态较正常对照组无明显差异，胞体饱满，遮光性强，细胞突起无回缩断裂，细胞数无减少。1.0mM浓度以上细胞胞体遮光性差，突起减少回缩，细胞数量较正常对照有所减少，且成剂量依赖性，浓度越大细胞数越少。
双重染色
通过Hoechst33342/PI双重染色估计细胞损伤情况，三七素干预组死亡细胞比慢性缺氧损伤组受损细胞明显减少（图2），可将损伤率由29.14% 降至 12.86%（图3）。
Claims (2)
1.三七素在制备治疗神经变性病药物中的用途。
2.根据权利要求1所述用途，其特征在于所述药物为片剂、胶囊剂、散剂、丸剂、颗粒剂、注射剂或乳剂。
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