CN111973587B - 槲皮素在制备抗草鱼呼肠孤病毒药物中的用途 - Google Patents
槲皮素在制备抗草鱼呼肠孤病毒药物中的用途 Download PDFInfo
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Abstract
本发明公开了槲皮素在制备抗草鱼呼肠孤病毒药物中的用途，槲皮素作为抗病毒活性成分用于制备抗草鱼呼肠孤病毒的药物，其应用剂量为0.1‑100μM/L。本发明发现槲皮素可以抑制GCRV病毒，且通过细胞水平实验证明槲皮素抗GCRV病毒效果良好，因其原料成本低廉，绿色安全，符合当前水产养殖绿色鱼药对安全、环保的要求，作为抗GCRV的水产养殖用绿色药物可满足抗GCRV病毒要求的同时，降低成本，便于大规模应用。
Description
技术领域
本发明属于水产养殖药物领域，具体涉及槲皮素在制备抗草鱼呼肠孤病毒药物中的用途。
背景技术
我国是水产养殖大国，草鱼(Ctenopharyngodon Idellus)是我国的主要经济养殖鱼类之一，草鱼由于饲料来源广、生长速度快及经济价值高而广受养殖人员的喜爱，养殖范围广且规模大，但草鱼抗病能力差，各个阶段都易受到病害感染，常见疾病有草鱼肠炎病、赤皮病、烂鳃病和病毒性出血病。由草鱼呼肠孤病毒(Grass Carp Reovirus，GCRV)引起的草鱼出血病是草鱼养殖中较为严重的传染病之一，发现的草鱼呼肠孤病毒株按照是否具有最外层吸附蛋白来分类主要有具有吸附蛋白的GCRV毒株如GCRV104株和GCRV106株，以及不具有吸附蛋白的GCRV毒株如GCRV-873株和GCRV-JX01株。目前，市场上主要采用草鱼呼肠孤病毒灭活疫苗和减毒活疫苗进行该病的防控，但是通过注射途径给鱼类使用疫苗费时费力，且注射过程中对鱼体有一定的损伤，因为鱼类免疫学的相关研究相较于哺乳动物还比较落后，导致鱼类疫苗对宿主的免疫保护期和保护率等指标仍然处于探索研究过程中，在中国市场上仅有一个针对不具有外衣壳蛋白基因型GCRV毒株的疫苗获得兽药证书，仍需要广泛开发针对不同基因型的广谱、高效、环境友好且价格低廉、稳定性好的病毒性草鱼出血病防控药物。
槲皮素(Quercetin)，是一种广泛存在于自然界的天然黄酮类化合物，已经发现它具有多重生物活性，如抗氧化、抗病毒、抗炎作用，在细胞和动物实验中可以用来治疗肝、心、脾、肺、肾、骨科疾病、神经系统疾病等，具有抗氧化、抗炎、抗病毒、抗肿瘤、降糖、降脂、免疫调节等生物活性和广泛的药理学作用，对治疗细菌感染、病毒感染、肿瘤、糖尿病、高血脂和免疫系统疾病均具有十分重要的临床意义，但是在水产养殖抗病毒方面的研究十分有限，专利申请(公开号：CN 107668327 A)公开了槲皮素金属螯合物在动物饲料添加剂的应用，槲皮素和金属离子结合具有很好的抗应激、抗氧化、消炎、抗菌作用，对动物的生长发育、治疗动物腹泻具有很好的作用。专利申请(公开号：CN 106260742 A)公开了抗氧化剂在消减动物体内真菌毒素残留中的应用，通过在对虾饲料中添加槲皮素、芦丁或者茶多酚诱导剂来诱导染毒对虾肠道内源解毒酶的活性来加速对虾体内毒素的代谢，降低或清除毒素的残留，确保对虾食品安全，但尚未发现利用槲皮素防控水生动物病毒的研究报道。
发明内容
本发明的主要目的是，提供槲皮素在制备抗草鱼呼肠孤病毒药物中的用途。
为实现上述发明目的，采用的技术方案是：槲皮素在制备抗草鱼呼肠孤病毒药物中的用途。
根据本发明的一些实施方案，所述抗草鱼呼肠孤病毒药物以槲皮素为活性成分，且所述槲皮素的应用剂量为0.1-100μM/L，优选为25-50μM/L。
根据本发明的一些实施方案，所述抗草鱼呼肠孤病毒药物还包括药学上可接受的辅料。
根据本发明的一些实施方案，所述抗草鱼呼肠孤病毒药物的剂型包括片剂、粉剂、颗粒剂、胶囊或缓释剂。
根据本发明的一些实施方案，所述抗草鱼呼肠孤病毒药物的给药方式为拌饲投喂。
与现有技术相比，本发明首次发现槲皮素可以抑制GCRV病毒，且通过细胞水平实验发现槲皮素抗GCRV病毒效果良好，因其原料成本低廉，绿色安全且效果良好，符合当前水产养殖绿色鱼药对安全、环保的要求，将其作为抗GCRV的水产养殖用绿色药物，为水产防治GCRV提供新的途径。
附图说明
图1是槲皮素对CIK细胞的安全浓度检测。
图2是不同浓度槲皮素对两种类型GCRV的抑制效果，其中，(a)为GCRV104毒株，(b)为JX01毒株。
图3是50μM浓度的槲皮素对GCRV的抗病毒活性影响。
具体实施方式
下面结合附图和实施例对本发明的实施方案进行详细描述，但是本领域技术人员将会理解，下列实施例仅用于说明本发明，而不应视为限定本发明的范围。实施例中未注明具体条件者，按照常规条件或制造商建议的条件进行。所用试剂或仪器未注明生产厂商者，均为可以通过市购获得的常规产品。
槲皮素，分子式为
槲皮素作为一种广泛存在于自然界的天然黄酮类化合物，研究发现其具有多重生物活性，如抗氧化、抗病毒、抗炎作用，在细胞和动物实验中可以用来治疗肝、心、脾、肺、肾、骨科疾病、神经系统疾病等，具有抗氧化、抗炎、抗病毒、抗肿瘤、降糖、降脂、免疫调节等生物活性和广泛的药理学作用，临床上可望用于治疗细菌感染、病毒感染、肿瘤、糖尿病、高血脂和免疫系统疾病，如用于支气管炎及多痰炎症，辅助治疗冠心病及高血压等。可以通过以下任一生产方法得到：
(1)将山毛榉科的栎属植物的树皮磨碎成粉末，用热食盐水洗涤，用稀氨水抽提后，用稀硫酸中和。煮沸滤液，析出结晶而得；
(2)百合科植物洋葱等用95％乙醇提取；
(3)芸香苷(芦丁)提取物及槲皮苷、异槲皮苷、茴香苷、金丝桃苷、槲皮黄苷、腊梅苷等经芸香苷分解酶或酸性水溶液水解而得。
下面实施例中以草鱼肾脏细胞系CIK细胞验证槲皮素用于抗GCRV病毒的效果，采用的GCRV病毒为GCRV104毒株和GCRV-JX01株。
实施例1 槲皮素对CIK细胞的安全浓度检测
在草鱼肾脏细胞系CIK细胞上进行槲皮素安全浓度的检测，设置0-400μM的浓度梯度的槲皮素处理CIK细胞96h，收集每个处理组的所有细胞，使用MuseTM检测各个处理组的细胞活力，结果如图1所示。
由图可知，槲皮素在小于100μM浓度范围内对CIK细胞活性影响较小，细胞活性与NC对照组无明显差异(均为94％左右)，浓度大于100μM时对细胞活力影响较大，细胞活力小于90％。
实施例2 安全浓度内GCRV的抗病毒活性检测
将CIK细胞传到6孔板，待细胞基本长满整个孔板时加入病毒，孵育1h后去除上清，分别加入0、25、50、100μM的槲皮素，检测感染72h后各个浓度的病毒滴度，结果如图2所示。
由图可知，在安全浓度范围内槲皮素可以有效拮抗GCRV，并且呈现剂量依赖性。
实施例3 50μM槲皮素对GCRV不同时间点的抗病毒活性
将CIK细胞传到6孔板，待细胞基本长满整个孔板时加入病毒，孵育1h后去除上清，更换药物浓度为50μM的培养基继续培养，设置GCRV感染对照组和50μM浓度的槲皮素给药组，分别取24、48、72、96h的样品进行定量和WB检测，结果如图3所示。
由图可知，与感染对照组相比，50μM槲皮素处理组在各个时间点病毒滴度都要显著低于感染对照组，说明浓度为50μM的槲皮素抗GCRV效果好。
综上，本发明通过细胞实验首次发现槲皮素可以抑制GCRV病毒，且抗GCRV病毒效果良好，因其原料成本低廉，绿色安全且效果良好，符合当前水产养殖绿色鱼药对安全、环保的要求，将其开发为抗GCRV的水产养殖用绿色药物。
上述对实施例的描述是为了便于该技术领域的普通技术人员能理解和使用本发明。熟悉本领域技术人员显然可以容易的对这些实施例做出各种修改，并把在此说明的一般原理应用到其他实施例中，而不必经过创造性的劳动。因此，本发明不限于上述实施例。本领域技术人员根据本发明的原理，不脱离本发明的范畴所做出的改进和修改都应该在本发明的保护范围之内。
Claims (2)
1.槲皮素在制备抗草鱼呼肠孤病毒药物中的用途，所述槲皮素作为抗病毒活性成分用于制备抗草鱼呼肠孤病毒药物，其应用剂量为0.1-100μM/L；
还包括药学上可接受的辅料；
所述抗草鱼呼肠孤病毒药物的剂型包括片剂、粉剂、颗粒剂、胶囊或缓释剂，给药方式为拌饲投喂。
2.根据权利要求1所述的用途，其特征在于，所述槲皮素的应用剂量为25-50μM/L。
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