CN109674799B - 桦木酸在机体排铅以及制备排铅食品、保健品和药物中的应用 - Google Patents
桦木酸在机体排铅以及制备排铅食品、保健品和药物中的应用 Download PDFInfo
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- CN109674799B CN109674799B CN201910097333.3A CN201910097333A CN109674799B CN 109674799 B CN109674799 B CN 109674799B CN 201910097333 A CN201910097333 A CN 201910097333A CN 109674799 B CN109674799 B CN 109674799B
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Abstract
本发明提供了桦木酸在机体排铅以及制备排铅食品、保健品和药物中的应用，属于桦木酸的应用技术领域。所述桦木酸能够减少血铅、脑铅、肝铅、肾铅、骨铅的残留量，促进尿铅和粪铅的排出，达到很好的驱铅效果，从而减少了铅所致的组织损伤。桦木酸且安全有效，为开发更多治疗与铅中毒的天然药物活性成分提供新思路；同时扩宽了桦木酸的应用范围，具有重要的科学价值和医学意义。
Description
技术领域
本发明属于桦木酸的应用技术领域，尤其涉及桦木酸在机体排铅以及制备排铅食品、保健品和药物中的应用。
背景技术
铅是一种广泛存在的工业污染物，随着现代工业化的不断发展，人们接触到铅的机会也越来越多。铅也是环境中常见的多系统和多器官毒性的重金属元素。铅通过消化道、呼吸道以及皮肤进入机体，与体内某些蛋白质、酶和氨基酸内的官能团结合，由于较高的富积性和较低的体外排出率，造成铅对机体产生严重的毒性。进入机体的铅对骨组织、肝和肾等重要组织器官造成损伤。研究发现，侵入机体的铅70％～90％最后以磷酸铅形式沉积并附着在骨骼组织上，通过影响维生素D3的合成，抑制钙的吸收，引起骨代谢紊乱，进而造成骨质软化和疏松，严重者极易发生病理性骨折。血清中肝功能相关酶活力随铅剂量的增加呈现明显的上升趋势，使肝细胞发生水泡和颗粒变性以及局灶性坏死。急性铅中毒可造成可逆性的肾脏近曲小管重吸收障碍，慢性铅中毒会造成近曲小管损伤或坏死，发展成慢性铅性肾病。研究还发现，血铅<10μg/dL时，血铅水平与认知能力下降呈剂量-效应关系，并且血铅水平越低，认知能力与血铅浓度负相关性越强。铅对机体的损害是多方面的，涉及神经系统、造血系统、免疫系统、内分泌系统、泌尿系统、心血管系统、生殖系统、骨骼系统等各个方面。日益严重的环境铅污染严重地威胁着人类的生存和健康。
目前报道过的国内外排铅的主要方法有：1)螯合剂，如依地酸二钠钙和二巯基琥珀酸等药物治疗，该类药物驱铅周期短，治疗快，但是这类药物往往把机体不可缺少的钙、铁和锌等排出，引起元素平衡失调，同时有肝肾毒性，不宜长期连续服用；2)维生素类，如维生素C、维生素E和维生素D。补充维生素C减缓铅中毒症状，补充维生素E可以抵抗铅引起的过氧化作用；补充维生素D则可通过对钙磷的调节来影响铅的吸收和沉积，但维生素类药物不能促进铅的排出。3)锌、硒等营养素，利用锌、硒与铅具有拮抗作用，从而阻止了机体对铅的吸收，但此拮抗效率有限，并不能减少组织内铅的残留量。4)天然产物类，在排铅方面有显著效果。如绿豆提取物可以增加铅中毒大鼠的铅排出量，降低骨铅和肝铅，提示绿豆提取物具有促进铅的排出和减少体内铅蓄积的作用。如金樱子通过增加尿液和粪便中铅的排出，从而阻止了机体对铅的吸收，同时，金樱子中的钙、铁、锌、硒等微量元素与铅具有拮抗作用，从而阻止了机体对铅的吸收达到良好的排铅效果。由此可见，寻找一种排铅效果好，副作用低，服用方便，可供日常保健的天然驱铅药物具有十分重要的意义。
发明内容
有鉴于此，本发明的目的在于提供桦木酸在机体排铅以及制备排铅食品、保健品和药物中的应用。
为了实现上述发明目的，本发明提供了以下技术方案：
桦木酸在促进机体排铅中的应用。
桦木酸在制备排铅食品中的应用。
桦木酸在制备排铅保健品中的应用。
桦木酸在制备排铅药物中的应用。
桦木酸在制备降低高铅模型小鼠脏器指数的药物中的应用。
优选的，所述脏器包括肝脏、大脑、肾脏、肺脏和心脏。
桦木酸在制备提高高铅模型小鼠脾脏指数和睾丸指数的药物中的应用。本发明的有益效果：本发明提供了桦木酸在机体排铅以及制备排铅食品、保健品和药物中的应用；所述桦木酸能够减少血铅、脑铅、肝铅、肾铅、骨铅的残留量，促进尿铅和粪铅的排出，达到很好的驱铅效果，从而减少了铅所致的组织损伤。桦木酸对铅中毒具有预防性保护作用和治疗作用，且安全有效，为开发更多治疗与铅中毒的天然药物活性成分提供新思路；同时扩宽了桦木酸的应用范围，具有重要的科学价值和医学意义。
附图说明
图1为桦木酸预处理对高铅小鼠体重的影响；
图2为桦木酸预处理对高铅小鼠器官指数的影响，其中A为桦木酸预处理对高铅小鼠大脑和肾脏脏器系数的影响；B为桦木酸预处理对高铅小鼠肝脏系数的影响；C为桦木酸预处理对高铅小鼠脾脏、肺脏和心脏系数的影响；D为桦木酸预处理对高铅小鼠睾丸系数的影响；
图3为桦木酸预处理对高铅小鼠组织铅残留量与血液中铅含量的影响；
图4为桦木酸预处理对高铅小鼠尿液与粪便中铅含量的影响。
具体实施方式
本发明提供了桦木酸在促进机体排铅中的应用。本发明中，所述桦木酸能够减少血铅、脑铅、肝铅、肾铅、骨铅的残留量，促进尿铅和粪铅的排出，达到很好的驱铅效果，从而减少了铅所致的组织损伤。
本发明还提供了桦木酸在制备排铅食品、保健品和药物中的应用。本发明对所述桦木酸的来源没有特殊要求，采用本领域常规市售桦木酸即可。在本发明中，所述食品、保健品和药品中桦木酸的含量优选为1～99％，更优选为5～95％；本发明对所述食品、保健品和药品的剂型没有特殊限定，采用本领域常规的剂型即可；所述食品、保健品和药品中优选的还可以包括辅料，本发明对所述辅料的种类和用量没有限定。本发明中，所述食品、保健品和药物的用量，优选的以所述食品、保健品和药物中桦木酸的质量计，优选的为0.5～10mg/Kgb w，更优选为2～8mg/Kg b w。
本发明提供了桦木酸在制备降低高铅小鼠模型脏器指数的药物中的应用。本发明中所述脏器包括肝脏、大脑、肾脏、肺脏和心脏。在本发明中，所述高铅小鼠模型的肝脏、大脑、肾脏、肺脏和心脏的脏器指数均升高，而桦木酸能够有效的降低所述高铅小鼠模型的肝脏、大脑、肾脏、肺脏和心脏的脏器指数。
本发明提供了桦木酸在制备提高高铅小鼠模型脾脏指数和睾丸指数的药物中的应用。本发明中，所述高铅小鼠模型的脾脏指数和睾丸指数均下降，而桦木酸能够有效的提高所述高铅小鼠模型的脾脏指数和睾丸指数。
下面结合实施例对本发明提供的技术方案进行详细的说明，但是不能把它们理解为对本发明保护范围的限定。
实施例1
桦木酸预处理对高铅小鼠的保护效果
1、试验动物及试验设计
健康雄性KM小鼠60只，4-5w，SPF级，体重(20±2)g，许可证号：(湘)2009-0004，饲料为M02小鼠普通育成料，小鼠和饲料购自湖南斯莱克景达实验动物公司。小鼠置于(22-25)℃，相对湿度为50％～70％的饲养房中，饲养1w后，随机分为6组，即空白对照组，醋酸铅组(模型对照组)，桦木酸低、中、高剂量+醋酸铅组(桦木酸分别按0.5、2和8mg/kg b w给与)，依地酸二钠钙组(阳性对照组)。各组给药方法如下：空白对照组采用自由饮水和基础饲料，其余5组每日饮用0.1％醋酸铅溶液，制备预防性高铅小鼠模型，同时，桦木酸低、中、高剂量+醋酸铅组分别灌胃0.5mg/kg、2mg/kg和8mg/kg的桦木酸，连续30d；阳性对照组小鼠肌肉注射75mg/kg b w依地酸二钠钙，每周连续注射给药3d后，停止给药4d，连续4周。并于末次给予桦木酸24h后，称量小鼠体重，取晨尿、粪便，眼眶采血扑杀，收集血液。小鼠颈椎脱臼而死，取内脏器官和股骨并进行各项指标检测。将收集的小鼠尿样、血样置于-22℃中保存待测，将大脑、肝脏、肾脏、股骨、粪样于烘箱中105℃干燥至恒重，置于研钵中粉碎后进行湿式消化，于石墨炉原子吸收分光光度计测定铅含量。
2、结果
(1)桦木酸预处理对高铅小鼠体重的影响
从表1和图1可以看到，各剂量组小鼠初始体重无差异；与空白对照组相比，醋酸铅组小鼠终末体重有所降低，而桦木酸能拮抗醋酸铅引起的体重下降，但差异不显著。
表1桦木酸预处理对高铅小鼠体重的影响(mg)
(2)桦木酸预处理对高铅小鼠器官指数的影响
从表2和图2可知，醋酸铅能明显增加小鼠肝、肾、脑、肺脏和心脏的脏器指数，桦木酸能明显降低这种增加，呈剂量依赖正相关。这说明醋酸铅能引起内脏器官水肿，从而导致损伤，而桦木酸具有预防性保护作用。同时，醋酸铅降低睾丸和脾脏的脏器指数，而桦木酸能拮抗这种降低，恢复睾丸和脾脏的脏器指数。这可能是醋酸铅影响机体的免疫力，使脾脏淋巴细胞减少，导致免疫器官萎缩。同时，醋酸铅可能引起生殖细胞数量减少，导致睾丸指数下降。而桦木酸，能恢复免疫器官和睾丸指数，从而提高机体的免疫力。
表2桦木酸预处理对高铅小鼠器官指数的影响(mg/g)
与对照组相比，“*”差异显著(P<0.05)，与醋酸铅组相比，“#”差异显著(P<0.05)，下同。
(3)桦木酸预处理对高铅小鼠组织铅残留量与血液中铅含量的影响
从表3和图3中可知，醋酸铅引起小鼠股骨、肝、肾、大脑组织和血液中铅含量极显著增加，当用桦木酸预处理后，有效降低股骨、肝、肾、大脑组织和血液中铅的含量，并且呈剂量依赖。说明桦木酸能减少铅在机体组织中的残留。
表3桦木酸预处理对高铅小鼠组织铅残留量与血液中铅含量的影响
与对照组相比，“**”差异极显著(P<0.01)，与醋酸铅组相比，“#”差异显著(P<0.05)，“##”差异极显著(P<0.01)，下同。
(4)桦木酸预处理对高铅小鼠尿液与粪便中铅含量的影响
从表4和图4中可知，桦木酸预处理后，能有效增加尿液和粪便中铅的含量，并且呈剂量依赖。说明桦木酸能促进重金属铅的排出。
表4桦木酸预处理对高铅小鼠尿液与粪便中铅含量的影响
实施例2
桦木酸对高铅小鼠的治疗作用
1、试验动物及试验设计
健康雄性KM小鼠40只，4-5w，SPF级，体重(20±2)g，许可证号：(湘)2009-0004，饲料为M02小鼠普通育成料，小鼠和饲料购自湖南斯莱克景达实验动物公司。小鼠置于(22-25)℃，相对湿度为50％～70％的饲养房中，饲养1w后，随机分为4组，每组10只。即空白对照组，醋酸铅组(模型对照组)，桦木酸组(按8mg/kgb w给与)，依地酸二钠钙组(阳性对照组)。所有动物每日均自由饮水，进食，给予标准饲料、去离子水。空白对照组每日腹腔注射0.9％氯化钠(与醋酸铅注射量相当)，其余组腹腔注射10mg/kg醋酸铅溶液，连续7d，建立高铅模型。停止注射醋酸铅溶液3d后，空白对照组和醋酸铅组小鼠灌服1％的可溶性淀粉，桦木酸组将8mg/kg桦木酸混悬于1％可溶性淀粉进行灌胃，阳性对照组则给予依地酸二钠钙15g/kg bw，连续给药20d，并于末次给药24h后，称量小鼠体重，取晨尿、粪便，眼眶采血扑杀，收集血液。小鼠颈椎脱臼而死，取内脏器官和股骨并进行各项指标检测。将收集的小鼠尿样、血样置于-22℃中保存待测，将大脑、肝脏、肾脏、股骨、粪样于烘箱中105℃干燥至恒重，置于研钵中粉碎后进行湿式消化，于石墨炉原子吸收分光光度计测定铅含量。
2、结果
(1)桦木酸对高铅小鼠体重的影响
从表5可以看到，各剂量组小鼠初始体重无差异；与空白对照组相比，醋酸铅组小鼠终末体重下降了9.81％，用桦木酸治疗后能拮抗醋酸铅引起的体重下降，与醋酸铅组相比，小鼠体重增加了7.46％，但差异不显著。
表5桦木酸对高铅小鼠体重的影响(mg)
(2)桦木酸对高铅小鼠器官指数的影响
表6桦木酸对高铅小鼠脏器指数的影响(mg/g)
从表6可知，醋酸铅能引起小鼠肝、肾、脑、肺脏和心脏的脏器指数增加，睾丸和脾脏的脏器指数降低，而桦木酸能拮抗醋酸铅对脏器指数的影响。特别是对肝、肾作用显著(P<0.01)。
(3)桦木酸对高铅小鼠组织铅残留量、血液、尿液以及粪便中铅含量的影响
从表7中可知，醋酸铅引起小鼠股骨、肝、肾、大脑组织、血液、尿液以及粪便中铅含量极显著增加，说明建立了高铅模型；当用桦木酸治疗后，有效降低股骨、肝、肾、大脑组织和血液中铅的含量，说明桦木酸能减少铅在机体组织中的残留；同时桦木酸增加尿液和粪便中铅的含量，说明桦木酸能促进重金属铅的排出。
表7桦木酸对高铅小鼠铅含量的影响
由上述实验可知，桦木酸可以减少铅在机体组织中的残留，加速铅在尿液和粪便中的排出，达到很好的驱铅效果，从而减少了铅所致的组织损伤。
以上所述仅是本发明的优选实施方式，应当指出，对于本技术领域的普通技术人员来说，在不脱离本发明原理的前提下，还可以做出若干改进和润饰，这些改进和润饰也应视为本发明的保护范围。
Claims (6)
1.桦木酸在制备排铅食品中的应用。
2.桦木酸在制备排铅保健品中的应用。
3.桦木酸在制备排铅药物中的应用。
4.桦木酸在制备降低高铅模型小鼠脏器指数的药物中的应用。
5.根据权利要求4所述的应用，其特征在于，所述脏器包括肝脏、大脑、肾脏、肺脏和心脏。
6.桦木酸在制备提高高铅模型小鼠脾脏指数和睾丸指数的药物中的应用。
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