【作者】 王伟；

【导师】 谭晓梅；

【作者基本信息】 第一军医大学 ， 中药药剂学， 2004， 硕士

【摘要】 高脂血症是指脂肪代谢或运转异常使血浆一种或多种脂质高于正常。可表现为高胆固醇血症、高甘油三酯血症或两者兼有。它与多种疾病关系密切，尤其是促进动脉粥样硬化、冠心病发展最危险的因素之一。由于中药制剂具备疗效肯定、配方灵活，副作用少，开发成本低，药物食品化等一系列优点，使其成为治疗高脂血症药物研发工作中的新亮点。 目的：研究精制山荷降脂方最佳提取精制工艺；评价精制山荷降脂方对高脂血症大鼠模型的治疗效果。 方法：(1)以山楂总黄酮含量、浸膏得率为指标，对索氏提取法、超声提取法、回流提取法及水煎煮提取法4种不同提取方法进行考察，并进一步对大孔树脂吸附法考察山楂的纯化工艺； (2)以荷叶总生物碱含量、干膏得率为指标，对酸水渗漉法、乙醇回流提取法及酸水回流提取法3种不同提取方法进行考察，并进一步对有机溶剂萃取法、醇提水沉法与离子交换树脂分离法，三种精制工艺进行比较，并建立荷叶的纯化工艺； (3)用高效液相色谱法测定泽泻醇相对峰面积，对水煎煮法、水提醇沉法及乙醇回流法3种不同提取方法进行了考察； (4)建立高脂血症大鼠模型，使用精制山荷降脂方治疗21d后，观察各组大鼠血生化指标、体重、肝脏重量系数及肝脏病理切片变化情况； (5)以上各组实验均通过正交设计及统计学方法对结果进行分析。 结果：(1)确定了从山楂中提取山楂总黄酮的工艺流程：首先采用乙醇回流法提取，进而使用大孔树脂吸附法进行精制； (2)确定了从荷叶中提取荷叶总生物碱的工艺流程：首先采用乙醇回流法提取，进而使用离子交换树脂分离法进行精制； (3)初步确定了使用乙醇回流法从泽泻中提取泽泻醇的工艺流程： (4)高脂模型组大鼠血清总胆固醇、甘油三酯、低密度脂蛋白值均明显高于空白对照组，成功建立了实验性血脂紊乱大鼠模型。(5)血清总胆固醇在高剂量组及阳性对照组显著降低;血清低密度 脂蛋白在高剂量组、中剂量组及阳性对照组显著降低;血清甘 油三酷在高剂量组与阳性对照组显著降低;体重在各治疗组均 有显著降低;肝脏重量系数指标仅在高剂量组有显著降低。但 高密度脂蛋白与极低密度脂蛋白在各治疗组均无明显降低。(6)肝脏病理切片显示:模型组肝细胞发生脂肪变性;低、中剂量 给药组和血脂康给药组，肝细胞胞浆疏松化;高剂量给药组肝 细胞与正常组相同。讨论:研制安全、有效、效应成分明确、质量可控的治疗高脂血症药物 是当前药物学研究热点之一;能够简便、高效的进行生产是药物 工业化生产的主要目标。通过本实验，我们初步观察并证实了精 制山荷降脂方对高脂血症的治疗效果并提出了最佳工艺流程，为 今后进一步开展药物作用机理与产业化研究奠定了坚实的基础。更多还原

【Abstract】 Hyperlipoidemia (HL) has been defined as one or more kinds of lipids are higher than normal standard in blood plasma due to lipids abnormal metabolism and transfer. It consists of hypercholesteremia, hypertriglyceridemia or both of them. It is associated with many diseases especially atherosclerosis and coronary artery disease (CAD). At present, many kinds of medicines are designed for controlling HL, whereas the results are limited. On the other hand, Chinese medicine pharmaceutics with many advantages such as affirmative therapeutic effects, prescription agilities, few side effects, low development costs and food-like dosage form is promising in new medicine development for HL.Objective:To study the best extract (EXT) craftflow-sheet of the depurated Shan-he-jiang-zhi (SHJZ) recipe; to evaluate the therapeutic efficacy on the rat model with Hyperlipoidemia made by the upgraded Shan-he-jiang-zhi recipe.Methods: (1) By means of the content of the crataegus total flavonoids as the indicatrix, inspecting the four different extracting method with Soxhlet extraction, ultrasound extraction, refluxing extraction and decoction extraction, further more investigating the depurating craft of the Crataegus by macroporous resin adsorptive process.(2)By means of the content of the lotus leaf total alkaloids and the yield of the xero-mastic as the indicatrix, inspecting the three different extracting method with acid-water percolation method ,alcohol refluxing extraction and acid-water refluxing extraction; further more comparing the organo-solvent extraction(Sx) with the method extracted by alcohol and pepted by water and ion-exchange resin separation; finally establishing the depurating craft of the Lotus leaf.(3)To determine relative peak area of alismol by high-efficiency liquid chromatography (HPLC ) , inspecting the three different extracting method with water refluxing extraction, the method extracted by water and pepted byalcohol and alcohol refiuxing extraction.(4)Establishing the rat model with Hyperlipoidemia,observating each ratgroup in such indicator :blood biochemical indicator, body mass(BM), Livercoefficient and variation in Liver pathological section after using thedepurated Shan-he-jiang-zhi recipe for 21d.(5)All the experiment above is designed by orthogonal design and the result isanalyzed by statistics method.Results: (1)Determine the craft flow-sheet extracting Crataegus total flavonoids from Crataegus: first extracting it using the refiuxing extraction, then depurating using macroporous resin adsorptive process.(2)Determine the craft flow-sheet extracting the Lotus leaf total alkaloids from Lotus leaf: first extracting it using the alcohol refiuxing extraction, then depurating using macroporous resin ion-exchange resin (IER) separation. (3)Initially determine craft flow-sheet extracting the Alismol from Alisma L. orientale Juzep.: using alcohol refiuxing extraction.(4)The blood-serum total cholesterol (TC), triglyceride (TG)and the low-density Hpoprotein (LDL) in the rat of the high-axungia group are obviously higher than those in the blank group, established the experimental blood fat disorded rat model successfully.(5)The blood-serum total cholesterol in the rat of the large dose group and positive control group is depressed obviously; the blood-serum low-density Hpoprotein in the rat of the large dose group ,middle dose group and positive control group is depressed obviously; the blood-serum triglyceride in the rat of the large dose group and positive control group is depressed obviously; the body weight of the rat in every group is lost obviously; the Liver indicatrix is depressed obviously only in the rat of the large dose group, while the high density Hpoprotein (HDL)and the very low density Hpoprotein(VLDL) has not any visible loss.(6)The variation in Liver pathological section presented that: adipose degeneration has happened in the liver cells of the rat in the model group ;liver cells endochylema puffing in the rat of the large dose group ,the middle dose更多还原