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新疆芹菜籽和苦豆子活性成分的药效学、毒理学实验及苦豆子降血脂分子生物学机制研究
李岳
学位类型硕士
导师阿吉·艾克拜尔艾萨
2004-06-10
学位授予单位中国科学院研究生院
学位授予地点北京
学位专业微生物学
关键词苦豆子 中药 高脂血症 活性成分 动物模型
摘要高脂血症是一种常见的脂代谢紊乱性疾病,它主要是指血清总胆固醇(TC)、 甘油三醋(TG)、极低密度脂蛋白胆固醇(VLDL-Ch)水平过高或血高密度脂蛋白胆 固醇(HDL-Ch)水平过低,它是构成动脉粥样硬化的一个重要因素,是公认的高 血压,冠心病和脑血管意外的主要危险因素,同时它又与许多疾病相关。因此, 纠正脂代谢紊乱,对改善冠心病、高血压及相关疾病的症状,降低脑血管意外的 发生具有十分重要的意义。目前治疗高脂血症的药物多为西药,但其中许多药物副作用较大且价格昂 贵。从天然产物中寻找疗效好、副作用小的降血脂药物已经成为国内外科技人员 研究的热点。本文的工作就是通过有机化学的技术方法提取了两种新疆地产中药材的活 性成分,应用目前药学界普遍使用的高脂血症动物模型筛选法筛选降血脂药物。 为了建立能客观体现药物作用的高脂血症动物模型,首先设计了几种不同造模方 法优缺点比较的实验,挑选出了最佳造模方法及时间。在经过初步的毒理学实验, 确定安全剂量后,采用了灌胃给药的方式进行药效学实验。实验证明:两种药物 的活性成分均能显著降低高脂血症大鼠血清中总胆固醇(TC)、甘油三醋(TG) 水平,同时苦豆子活性成分(K-1)还具有抗氧化及治疗脂肪肝的作用。在研究 药物作用机理的实验中,设计了在脂代谢中起重要作用的脂蛋白脂酶(LPL)基 因及与纤溶作用相关的纤溶酶原激活物抑制物1型(PAI-1)基因的引物,应用 半定量逆转录PCR(PCR)技术扩增出了大鼠肝脏组织内的目的基因,激光 扫描比较基因表达差异。实验研究发现:苦豆子活性成分能提高LPL基因的 mRNA表达水平,调整血脂紊乱。同时苦豆子活性成分能降低PAI一1’基因的 mRNA表达水平,说明药物具有抑制动脉粥样硬化及血栓形成的作用。新疆苦豆子资源丰富,但基本没有得到开发利用。本文的研究为苦豆子在作 为降脂药物研究方面做了生物化学基础工作,期望能为我区苦豆子资源开发及经 济的发展发挥有益的作用。
其他摘要Hypercholesterolemia is now a common disease in the world. It's induced by the lipid metabolism mass. The high level of the total cholesterol and total triglyceride, the low level of the high density lipoprotein are also the risk factor for coronary heart disease. So, how to cure the Hypercholesterolemia and blow-down the high level of high TC,TG have a significant meaning. Recently, the curing medicines are mostly the chemical medicine 0 Some of them have seriously accessory responds and very expensive. Moreover, finding the drug that can cure the hypercholesterolemia from Chinese traditional medicine became the hot-point to researchers. Now, finding of the new drugs from the natural production is a common method that many Chinese researchers preferential chose. It has became the hotspot for new drugs research Our ideas are extract the active domain from the aimed Chinese traditional medicine, then using the hypercholesterolemia animal model screen out the active domain that can reduce high-level cholesterol of animals from the Uigur drug. For establish a impersonality animal model, the four model building method were compared, then found out the best method and experiment times. Finally we accomplished the experiment from the irrigate method under the safety dose after the accident toxicological experiments. It's proved that the Sophora alopecuroides's active domain(K-l) can reduce the TC and TG level significantly in rat's blood serum. It also told that K-1 has antioxidants activity and can cure seteatosis. In order to discovery the complex therapeutic mechanism of the K-1, we used the RT-PCR method doing the gene expressing research. After designed the prime of PAI-l(a gene osculated related to the fibrinolysis system) and LPL(a gene do a important part in the lipoprotein metabolize), we used RT-PCR method enlarge the aimed genes of rat liver, then compared their difference by laser scan. Finally we found the K-1 can enhance the expression level of LPL, regulate the lipid turbulence.K-1 can also reduce the expression level of PAI-1, restrain the develop of atherosis and thrombus. Xinjiang have abundant Sophora alopecuroides resource. But it's almostly not be impoldered. Empoldered the Xinjiang's Sophora alopecuroides resource will have a deep effect to Xinjiang's curatorial industry developing and can drive the local economy.
文献类型学位论文
条目标识符http://ir.xjipc.cas.cn/handle/365002/4455
专题资源化学研究室
作者单位中国科学院新疆理化技术研究所
推荐引用方式
GB/T 7714
李岳. 新疆芹菜籽和苦豆子活性成分的药效学、毒理学实验及苦豆子降血脂分子生物学机制研究[D]. 北京. 中国科学院研究生院,2004.
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