灵芝菌株改善学习记忆作用及其机制研究

【作者】 曾瑾；

【导师】 孟宪丽；

【作者基本信息】 成都中医药大学 ， 药理学， 2008， 硕士

【摘要】 灵芝收载于《中国药典》2005年版第一部,为多孔菌科真菌赤芝Ganodermalucidum(Leyss.ex Fr.)Karst.或紫芝Ganoderma sinense Zhao,Xu et Zhang的干燥子实体。具有补气安神、止咳平喘的功效。由于目前进行灵芝栽种、品种选育的多为农业科学工作者,使其缺乏“传统药材”的系统研究;其次灵芝本身存在菌株间的化学成分差异和功效差异的情况,加之我国的食药用菌品种登记制度尚未完善,造成我国灵芝资源品种混杂:而目前我国针对不同灵芝品种进行药效特异性研究的报道较少。因此,不同灵芝品种的混用制约了其更好的应用和开发。灵芝是亚洲国家常用的抗衰老药物,现代药理研究表明灵芝具有抗肿瘤、调节机体免疫功能、治疗心脑血管疾病的作用,而对灵芝的神经保护作用研究甚少。针对上述现象,本论文采用了菌株拮抗实验及栽培实验对8株不同灵芝菌株的表型遗传差异性进行了初步研究;并对不同灵芝菌株进行了改善学习记忆的药效学筛选实验;将筛选出作用较显著的菌株(ZL2)采用经典行为学方法,研究该灵芝菌株改善学习记忆的药效作用;并采用胆碱递质测定的实验方法,研究其对神经递质的影响:还考察其在体外对PC12细胞增殖的影响,在细胞水平上对其神经保护作用机制进行了探讨。结果表明:1.供试菌株间都存在明显的表型遗传差异和药效差异,其中ZL3与ZL4菌株表型遗传差异性较小,亲缘关系相对较近,其余灵芝菌株拮抗关系强,表型遗传差异较大。不同菌株间的药效差异的存在对灵芝的药效品质有着较大影响。2.药效学实验研究中,灵芝菌株ZL2具有明显的改善学习记忆的作用。具体表现为:ZL2灵芝菌株可提高不同损伤模型动物的学习记忆能力,并对学习记忆不同阶段均有正向影响。3.在机制探讨中,ZL2灵芝菌株改善学习记忆的作用的可能机制为:提高脑组织内乙酰胆碱含量、降低胆碱酯酶活力;诱导神经元的分化,对抗β淀粉肽导致的神经毒性及氧化损伤。综上所述,不同的灵芝菌株间存在着遗传差异及药效品质的差异,其中ZL2灵芝菌株具有改善学习记忆作用,作用机制可能是提高脑组织内乙酰胆碱含量、降低胆碱酯酶活力,诱导神经元的分化,对抗β淀粉肽导致的神经毒性及氧化损伤。更多还原

【Abstract】 PartⅠof the 2005 edition "Chinese Pharmacopoeia" containing Ganoderma for the dry.carpohole of Ganoderma lucidum(Leyss,ex Fr.) Karst or Ganoderma sinense Zhao,Xu et Zhang.It has a function of invigorating Qi for tranquilization,relieving cough and asthma.As the research of growing and breeding of Ganoderma is mostly worked by agricultural scientists,it lack of systematic research of this "traditional medicine".Moreover,medical fungus registration system in china has not been perfect, this also result in hybrid varieties of fungus resources,genetic relations unclear.And varieties species have differences in chemical composition and pharmacologic action. So the confusion of varieties Ganoderma species in clinical application restrict it’s develop and application.Ganoderma is commonly used by Asian countries as antiaging agent,modern pharmacological research show that Ganoderma has strong abilities of anti-tumor, regulating immune function,treating cardiovascular and cerebrovascular diseases.But the research of it’s protective effect of the nerve is very little.In response to these phenomenon,in this paper,Genetic specificity of eight different strains of Ganoderma had been studied preliminarily,screening test of different strains of the fungus in improving the effect on learning and memory had been done and the water maze test and step-though test were carried out to explore the changes of the rats’ learning and memory capacities by the selected Ganoderma strains,ZL2.The selected strains,ZL2,had been explored the changes of the rats’ learning and memory abilities by maze test and step-though test.Determination of Cholinergic neurotransmitter as a method has been adopted to study it’s effect on neurotransmitter.We used an in vitro model system,PC12 cells,to observe the resistive effects of serum and cerebrospinal fluid containing ZL2 on neurotoxicity induced by Beta-amyloid protein.The results showed that:1.There are strong antagonistic relationships and obvious phaenotype genetic specificity of different sources of 8 strains,except ZL3 and ZL4.2.Behavior experimental study show that ZL2 presented evident effects on learning and memory.ZL2 can improve learning and memory capacities of normal animals,aged mice,animals injuried in learning and memory capacities,and have positive effects on learning and memory on different stages. 3.Mechanism explore show that the improving effect on learing and memory of ZL2 has relationship with the increase of content of acetylcholine in cerebrum and the decrescence of acetylcholine esterase enzyme activity.Role in nerve protection,ZL2 promote proliferation of PC12 and resist the neurotoxicity induced by Beta-amyloid proteinIn short,different kinds of Ganoderma strains have genetic specificity and different pharmacological properties.The selected strains of fungus,ZL2,presented promising effects on learning and memory,the mechanism has relationship with the increase of acetylcholine content in cerebrum and the decrescence of acetylcholine esterase enzyme activity,also has relationship with neuroprotective effect.更多还原