CN105193784B - 银杏素在制备治疗猪链球菌感染药物中的应用 - Google Patents
银杏素在制备治疗猪链球菌感染药物中的应用 Download PDFInfo
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Abstract
本发明公开了银杏素在制备治疗猪链球菌感染药物中的应用。本发明通过家兔红细胞溶血试验、巨噬细胞(J774)损伤的保护试验以及小鼠猪链球菌感染的治疗作用试验证实了银杏素对猪链球菌感染具有较好的治疗效果。本发明用银杏素治疗猪链球菌感染，与用抗生素治疗相比较，具有无耐药性，治愈率高的优点。因此银杏素可以用于抗猪链球菌感染新药开发,并对药物靶标确认有着重要意义。
Description
技术领域
本发明涉及银杏素在制备治疗猪链球菌感染药物中的应用，属于医药领域。
背景技术
银杏素存在于银杏科植物银杏的叶和外种皮中。银杏素具有多种生物学活性，还具有扩张血管和治疗心绞痛等作用。作为新型的天然功效因子，银杏素在食品工业、医药工业等方面具有重要的作用。但截至目前国内外未见银杏素治疗猪链球菌感染的报道。
猪链球菌病是一种严重的世界范围内流行的人畜共患传染病原菌，可导致人和动物的脑膜炎、败血症和心内膜炎；此外，也可引起肾脏、肝脏、肺脏和心脏等多脏器功能衰竭和死亡以及听力永久丧失。OIE将猪链球菌感染定为B类疾病，对公众健康造成很大的威胁。猪链球菌的致病力与其毒力因子密切相关，其中猪链球菌分泌的溶血素可使得病原菌逃逸宿主免疫***攻击以及突破血脑屏障而引起脑膜炎，甚至是死亡。因此溶血素是猪链球菌感染抗毒力药物研发的潜在靶标。近年来由于抗生素的滥用以及其不可避免地易诱导耐药性的发生和发展，因此迫切需要寻求新型、毒性小和选择压力小的抗感染药物。本发明首次发现无抗菌活性的银杏素可直接中和猪链球菌溶血素的成孔活性并体内外抑制猪链球菌的致病力。
发明内容
本发明的目的在于提供一种对猪链球菌感染具有治疗作用的抗毒力药物。
银杏素的分子结构如下：
本发明通过家兔红细胞溶血试验、巨噬细胞(J774)损伤的保护试验以及小鼠猪链球菌感染的治疗作用试验，证实银杏素可抑制猪链球菌溶血素的成孔活性以及其对猪链球菌感染具有治疗作用。
具体实施方式
1.溶血试验
纯化的猪链球菌溶血素于96孔板中作连续的二倍稀释，每个孔中加入107个家兔红细胞，于37℃中孵育30min后离心。其中使红细胞溶解的最高稀释倍数视为溶血滴度(Hemolysis titre)。
不同浓度银杏素处理下猪链球菌溶血素的溶血滴度如表1：
表1.银杏素对猪链球菌溶血素溶血活性的抑制作用
| 银杏素(μg/ml) | 溶血滴度(Hemolysis titre) |
| 0 | 4096 |
| 2 | 512 |
| 4 | 128 |
| 8 | 16 |
| 16 | 2 |
2.银杏素对猪链球菌介导J774细胞损伤作用的保护性试验
猪链球菌于THB培养基中培养至OD600nm＝0.8，取5ml的细菌培养物，离心并重悬于10ml的DMEM培养基中。J774细胞于DMEM培养基(加入10％胎牛血清)中于37℃，5％CO2培养24h后，以2×104个细胞/孔铺于96孔细胞培养板中，每孔200μl。细胞贴壁后，加入猪链球菌菌悬液(细菌：细胞＝5:1)，并加入不同浓度的银杏素，置于细胞培养箱中于37℃，5％CO2共培养5h。离心取100μl上清，并加入LDH试剂100μl，37℃孵育30min，后用酶标仪测570nm吸光值，计算不同浓度银杏素处理组细胞的存活率(表2)。结果表明银杏素能够保护猪链球菌对J774介导的细胞损伤，且该作用呈现剂量依赖性。
表2.银杏素抑制猪链球菌对J774介导的细胞损伤
| 银杏素(μg/ml) | 细胞死亡率(％) |
| 0 | 56.37±5.07 |
| 2 | 46.02±5.63 |
| 4 | 35.17±4.42 |
| 8 | 20.79±3.76 |
| 16 | 6.43±4.36 |
3.小鼠猪链球菌感染的实验治疗学研究
3.1小鼠猪链球菌感染模型
BALB/c小鼠(雄性，18-22g)经腹腔注射200μl猪链球菌悬液(1010CFU/ml)，建立小鼠猪链球菌感染模型。
3.2保护率试验
小鼠接种猪链球菌后2h分别皮下注射100、50和25mg/kg(100μl)的银杏素，每间隔6h给药一次。不给药对照组同时间皮下注射100μl生理盐水，每组50只小鼠。按给药方案给药后，分别记录小鼠感染猪链球菌24h、48h和72h后的死亡率。结果表明(表3)，经银杏素给药治疗后，显著降低小鼠猪链球菌感染的死亡率(P＜0.05)。
表3.银杏素降低小鼠猪链球菌感染死亡率
Claims (3)
1.银杏素在制备治疗猪链球菌感染药物中的应用。
2.如权利要求1所述的银杏素在制备治疗猪链球菌感染药物中的应用，其特征在于所述的猪链球菌感染是指由链球菌属细菌引起的细菌性感染，其中细菌性感染是指由猪链球菌引起的感染。
3.如权利要求1所述的银杏素在制备治疗猪链球菌感染药物中的应用，其特征在于所述的银杏素制剂为适合临床使用的抗猪链球菌感染的药物制剂，所述药物制剂是注射剂、胶囊剂、片剂或粉针剂。
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| CN111973585B (zh) * | 2020-09-08 | 2022-04-08 | 广州中医药大学第一附属医院 | 银杏双黄酮在制备抗髓系抑制性细胞的药物中的用途 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2005092324A1 (en) * | 2004-03-19 | 2005-10-06 | The Trustees Of Columbia University In The City Of New York | Ginkgolide compounds, compositions, extracts, and uses thereof |
| CN104940184A (zh) * | 2014-03-25 | 2015-09-30 | 上海医药工业研究院 | 一种银杏黄素类化合物的应用 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005092324A1 (en) * | 2004-03-19 | 2005-10-06 | The Trustees Of Columbia University In The City Of New York | Ginkgolide compounds, compositions, extracts, and uses thereof |
| CN104940184A (zh) * | 2014-03-25 | 2015-09-30 | 上海医药工业研究院 | 一种银杏黄素类化合物的应用 |
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