1、摘 要高血脂症是引发动脉粥样硬化的首要因素，而动脉粥样硬化所导致的心血管类疾病则是世界性首要疾病。虽然现今临床上所用的降血脂西药疗效确切，但其毒副作用比较大，不适宜长期服用。因此，开发出一种无毒且疗效好的降血脂类中药复方意义重大。本研究依据中医组方和现代药理研究，将药食同源的物质纳豆冻干粉、银杏叶提取物和丹参提取物作为主要原料，按照3.7：1：0.6比例进行组方，研发辅助降血脂功能的配方样品，通过动物实验对该配方的辅助降血脂作用机理进行初步探讨。本研究实验通过喂食高脂饲料一周建立高血脂症大鼠模型，使大鼠脂代谢紊乱，进而导致建模大鼠体重增长率以及血脂水平显著高于正常大鼠。建模一周后，空腹测量体重
2、值、大鼠血清总胆固醇以及血清甘油三酯水平（建模组与对照组相比较，若检测中血清TC、TG指标呈阳性（显著），则建模成功）。再对建模成功的大鼠使用样品的高剂量（样品总量900 mg/（kgd）、中剂量（样品总量300 mg/（kgd）、低剂量（样品总量100 mg/（kgd）以及1.2g五倍剂量（样品总量100 mg/（kgd）作为受试物进行灌胃处理28天，阳性对照组灌胃辛伐他汀（1.67 mg/kg ）和空白对照组（生理盐水）、毒理实验组（样品总量900 mg/（kgd）共8组进行灌胃（除空白对照组与毒理实验组用基础饲料，其余6组均喂食高脂饲料），在第28天取血后，使用商业试剂盒检测血清总胆固醇
3、、甘油三酯、高低密度脂蛋白以及抗氧化水平等来探究并验证由纳豆冻干粉、银杏叶提取物以及丹参提取物配伍的样品降低血脂的作用和效果，同时对肝脏组织进行组织切片制作，治疗组与空白对照组进行对照，进而观察该样品受试物对肝脏组织的效果与作用。该实验研究结果表明，该样品可使高脂大鼠体重显著降低并且降低血脂水平。这些有益的影响可能是因为该样品能够抑制脂质的机体内吸收，提高体内脂质代谢,降低血管内脂质过氧化程度，改善血管内皮功能，提高了高密度脂蛋白水平。该样品也能显著抑制高脂机体体重的增加，并且通过切片可知该样品有效地改善高脂带来的肝组织损伤，还可以增强抗氧化活性。纳豆、银杏叶和丹参三者均有降血脂的功效，并且临
4、床研究证明，它们中的两两结合均具有辅助降血脂的作用。本研究将三者按照一定的比例配伍，发挥协同作用，达到辅助降血脂的作用效果。因此，纳豆冻干粉、银杏提取物和丹参提取物的组方可以降低血清总胆固醇、甘油三酯和低密度脂蛋白水平，提高高密度脂蛋白水平，可以增强抗氧化活性。三种原料组方能够更好的抑制动脉粥样硬化，对预防和治疗心血管疾病具有重要意义，并且安全、有效、可长期服用。关键词：纳豆；银杏；丹参；高血脂症；抗氧化活性- II -Research of Traditional Chinese medicine extract on Hypolipidemic auxiliary activityAbst
5、ract Hyperlipidemia is the leading cause of atherosclerosis, and cardiovascular disease caused by atherosclerosis is the worlds leading disease. Although the clinical use of lipid-lowering agents in western medicine is effective, but its effects of toxic side are relatively large. And it is not suit
6、able for a long-term. Therefore, the development of a non-toxic and effective lipid-lowering drugs is of great significance. In this study, rats were fed with high fat diet for one week to establish hyperlipidemia model, which led to the disorder of lipid metabolism in rats, which led to the increas
7、e of body weight and blood lipid level in model rats, which was significantly higher than that in normal rats. One week after modeling, fasting body weight measurement value, serum total cholesterol and serum triglyceride levels (model group compared with the control group, if the detection of serum
8、 TC, TG index were positive (significant), while the success of modeling). The high dose of modeling in rats using the sample (sample 900 of the total mg/ (kg D), middle dose (sample) total 300 mg/ (kg D) and low dose (100 of the total sample mg/ (kg D) and 1.2g (100 of the total sample of five dose
9、s (kg mg/ d) as administered 28 days treatment, positive control group were administered with simvastatin (1.67 mg/kg) and control group (normal saline), experimental group (900 of the total sample toxicity of mg/ (kg - D) were divided into 8 groups by intragastric administration (except blank contr
10、ol group with basic diet, and toxicology in experimental group, the other 6 groups were fed with high fat diet), in twenty-eighth days after taking the blood, using a commercial kit for detection of serum total cholesterol, triglyceride, low density lipoprotein and antioxidant levels to explore and
11、verify the natto freeze-dried powder, Ginkgo biloba extract, salvia extract The compatibility of the sample decreased the function and effect of blood lipids, and tissue slice preparation on liver tissue, treatment group and blank control group, then observe the sample test on the effect and functio
12、n of liver tissue.Therefore, the sample can reduce serum total cholesterol, triglyceride and low-density lipoprotein levels, and enhance HDL levels, which can enhance antioxidant activity. Three ingredients can better inhibit atherosclerosis, and have important significance for the prevention and tr
13、eatment of cardiovascular disease, and safe, effective and long-term use.Key Words：Natto; Ginkgo biloba; Salvia miltiorrhiza; Hyperlipidemia; Antioxidant activity- VII -目 录摘 要IIAbstractIII1文献综述11.1 血脂及脂蛋白11.2 脂质代谢21.3 高血脂症31.3.1 高血脂症发病原因31.3.2与高血脂症相关的指标31.3.3 降血脂方法途径41.4降血脂药物51.5 纳豆51.5.1 纳豆活性成分61.5
14、.2 纳豆药理作用61.6 银杏叶71.6.1 银杏叶中的活性成分71.6.2 银杏叶提取物的药理作用81.7 丹参91.7.1 丹参中分离的化学成分91.7.2 丹参药理活性研究101.8 纳豆、银杏叶、丹参之间的功效研究111.8.1 纳豆与银杏配伍功效的研究111.8.2 银杏与丹参配伍功效的研究111.9 小结121.10 该实验研究具体内容122 复方药剂辅助降血脂功效的实验研究132.1 引言132.2 组方药物132.2.1 银杏叶提取物剂量132.2.2 丹参提取物剂量132.2.3 纳豆冻干粉142.3 实验材料与仪器142.3.1 实验材料与试剂142.3.2 实验仪器14
15、2.3.3 实验动物152.3.4 实验大鼠饲料152.3.5 实验剂量选择152.3.6 实验分组152.4 实验方法162.4.1 构建高脂大鼠模型162.4.2 高脂大鼠建模预实验162.4.3 动物实验设计192.4.4 样品对大鼠体重的影响192.4.5 样品对大鼠血脂水平的影响212.4.6 样品对大鼠肝脏形态及肝脂水平分析262.5 本章小结273 复方药剂对高脂血症大鼠抗氧化活性的影响283.1 引言283.2 实验材料与仪器283.2.1 实验材料与试剂283.2.2 实验仪器293.3 实验方法293.4 样品对大鼠抗氧化活性的影响293.5 本章小结31结论32参 考 文 献33致 谢351 文献综述1.1 血脂及脂蛋白血脂是血液中所含脂质的总称，是人体基础代谢必需的物质。其中总胆固醇(Total Cholesterol，TC)和甘油三酯(Triglyceride，TG)是血浆中主要血脂成分，血脂还包括磷脂、游离脂肪酸、类固醇、固醇和糖脂等脂质以及类脂。血液中所有脂蛋白所含有的胆固醇总和称作总胆固醇，分为游离胆固醇以及胆固醇酯。胆固醇是合成固醇类激素，胆汁酸、维生素D以