【作者】 刘冷；

【导师】 睢大员；

【作者基本信息】 吉林大学 ， 药理学， 2004， 硕士

【摘要】 高脂血症是引起动脉粥样硬化（AS）和心、脑血管疾病的重要危险因素。由于AS是冠心病的病理基础，而高脂血症又是导致AS的首要危险因素，预防和治疗高脂血症，对防止冠状动脉粥样硬化具有重要意义。苦碟子口服液(KDZOL)系由菊科植物抱茎苦卖菜[Ixeris Sonchifolia (Bge.)Hance]全草提取物制备的中药制剂，有效成分为腺苷及黄酮类物质。以抱茎苦卖菜为原料研制的碟脉灵注射液临床用于治疗脑血栓及冠心病心绞痛、心肌梗死等缺血性心脏病取得良好疗效。在临床用药过程中发现，碟脉灵注射液有较强的调节血脂及降低血液黏度作用，为将其开发成调血脂的保健药品，本文通过大鼠高脂血症模型，观察了KDZOL对实验性高脂血症大鼠血清总胆固醇、脂蛋白-胆固醇代谢的影响及其抗氧化作用。通过喂饲Wistar大鼠高脂饲料，建立实验性高脂血症模型，并分别给予苦碟子皂苷10g生药/kg/d、20g生药/kg/d、40g生药/kg/d，观察其对大鼠血清TC、TG、LDL-c、HDL-c含量，血清和肝组织中LPO含量及SOD活性的调节作用，同时测定血浆TXA2和PGI2浓度，并以非高脂血症大鼠和饲以山楂精高脂血症大鼠作对照，探讨KDZOL是否具有调血脂及防止AS的形成和发展作用。 高脂血症时，血清TC、TG、LDL-c含量升高，HDL-c水平降低。因此，通过监测血中TC、TG、LDL-c及HDL-c等浓度，不仅可以观察高脂血症的程度及发生AS和AS引起的缺血性心脑血管疾病的危险性，而且也是目前检验调脂药物最常用的生化指标之一。本实验结果表明，大、中剂量的KDZOL能降低高脂血症大鼠升高的TC、TG、LDL-c及TC/HDL-c、LDL-c/HDL-c比值，并且大剂量组可升高HDL-c。 高脂血症时伴有脂质过氧化作用的增强，使LPO含量增加，过量的LPO能使TXA2生成增多，PGI2合成减少，有利于血小板在受损的内皮细胞聚集，<WP=40>促使粥样班块形成；并且使LDL、胆固醇氧化修饰，促使AS的发生。SOD是体内清除自由基的主要抗氧化酶之一，它通过清除自由基，抑制LPO的生成，从而保护机体细胞免受过氧化脂质的损害。因此测定血浆LPO浓度及SOD活性，已被公认为防治AS及其引起的心血管疾病的常用指标。本实验结果表明，高脂血症大鼠血清LPO含量明显升高，SOD活性明显降低。大、中剂量的KDZOL能够改善脂质代谢， 降低脂质过氧化物含量，升高抗氧化酶活性，提高机体抗氧化能力，这可能是KDZOL调节血脂，预防AS发生的作用机制之一。 高脂血症时，引起血液流变学发生改变，可以通过抑制纤溶作用，影响血小板功能，增加全血和血浆粘度等诱导血栓形成而致AS发生。本实验观察到高脂血症大鼠全血低切、中切、高切粘度及血浆粘度均明显升高，KDZOL大、中两个剂量组对上述血液流变学参数的升高均有明显降低作用，表明KDZOL能降低高脂血症时血液的高粘状态，减少了AS发生的危险性。 PGI2具有消除氧自由基和抗氧化损伤的功能，同时它也是一种有效的血管扩张物质。PGI2与TXA2作用完全相反，在体内构成了PGI2/TXA2平衡调节系统。高脂血症时，血流中过多的胆固醇分子、动脉脂质堆积，过氧化脂质含量过高等均破坏血管内皮，使PGI2合成减少，TXA2增多，促使了AS的发生。KDZOL能明显升高高脂血症大鼠PGI2，降低TXA2水平，并明显提高PGI2/TXA2比值，可能对防止体内血栓形成和预防AS发生起重要作用。 综上所述：KDZOL能升高高脂血症大鼠HDL-c，降低TC、TG、LDL-c和LPO水平，升高SOD活性，并降低TC/HDL-c和LDL-c/HDL-c比值比值，降低全血粘度和血浆粘度；增加血浆PGI2水平，降低TXA2水平，表明KDZOL可能通过调节血浆脂蛋白-胆固醇代谢，改善血液粘稠度，增强抗氧化酶的活性，减少氧自由基损害等途径发挥防治AS的作用。更多还原

【Abstract】 Hyperlipidemia is a cardinal risk factor that induce atherosclerosis(AS) and cardia-cerebrovascular disease. Because AS is the pathology basis of coronary heart disease,and that hyperlipidemia is the major risk factor of causing AS, so it has important meaning to protect and cure hyperlipidemia which will prevent the coronary artery atherosclerosis. KDZOL is was isolated from the whole plant of Ixeris sonchifolia olia (Bge.) Hance. Its effective contains is flavonoids and adenoisine. Objective To study the effect of Diemailing injection with Ixeris Sonchifolia (Bge.)Hance as raw materaial on the treatment of brain-thrombusbrain-embolism cardia- cerebrovascular-disease myocardial- infarction cardiac-arrhythmia and so on is confirmed effectively. When Diemailing injection is applied in clinical treatment,we find it can obviously adjust bloodlipid and reduse bloodviscosity. So we develop it as adjusting blood-lipid health- medicine. All these demonstrate that KDZOL can protect acute myocardialischemia heart and the effects are superior on that of Diemailing. In this study we observed the influence of <WP=42>KDZOL on cholesterol, lipoprotein-cholesterol metabolism and anti-oxidation effect etc. of experiment hyperlipidemia rat to provide new idea for clinical cure of coronary heart disease angina and prevention of AS. The model of experiment hyperlipidemia was established by giving lipid-riched feeds to seventy-two Wistar rats.KDZOL with dosage 10g herbs/kg.d（low dosage group）、20g herbs/kg.d（mid-dosage group）、40g herbs/kg.d（high dosage group）was given to observe the adjusting effect of KDZOL on TC、TG、LDL-c、HDL-c concentration in rat’s serum，LPO concentration , SOD activity of serum and liver and the TXA2 and PGI2 of plasma was estimated .non-hyperlipemia rats and hyperlipemia rats feeding with Lovastatin was used as control group to verify whether the KDZOL have effect of adjusting plasma lipoprotein and anti-AS.When in hyperlipemia, the concentration of TC、TG and LDL-c decrease ,at the same time HDL-c increase. As satisefied adjusting bloodlipid medicine,should decrease the concentration of TC、TG、LDL-c、Apo-B and increase HDL-c Apo-A. So we investgate these results ,we can confirm that KDZOL with high and <WP=43>mid- dosage can decrease the raised TC、LDL-c concentration and TC/HDL-c、LDL-c/HDL-c ratio , and the high-dosage group can increase HDL-c of hyperlipemia rats.Reinforcement of Lipid peroxidation in hyperlipemia make the concentration of LPO increased. Excessive LPO induce AS by rising the TXA2 production , decreasing the PGI2, aggregating platelet in harmed endothelium.，facilitating atheromatous plaque formation and oxidizing the LDL and cholesterol .SOD, one of main anti-oxidase，protects the cell from harming of peroxidation lipid by removing free radical and inhibiting production of LPO. So the decreasing of the LPO and the activity of SOD in plasma is generally accepted as an useful index in evaluating the effect of drug applied in protection and cure of AS and cardiovascular disease related with AS.The result demonstrate that KDZOL with high and mid-dosage can ameliorate the lipid metabolism ,decrease the concentration of lipid peroxidation,increase the activity of anti-oxidase and improve the ability of anti-oxidation. These maybe one of the possible mechanism of KDZOL in adjusting plasma lipidprotein and prohibiting AS. <WP=44>Hyperlipemia, which refrain fibrinolytic effect, influence the function of platelet ,increase consistence of blood and plasma and induce the alteration of hemorheology etc.,cause AS. We observed that the blood viscosity of hyperlipemia rats raised markedly. KDZOL with high and mid-dosage can decrease the parameter of hemorheology of hyperlipemia rats distinctly. It demonstrate that KDZOL can decrease the hyperviscosity of blood，reduce the occurrence possibility of AS. PGI2 can eliminate the oxygen-derived free radical and inhibit oxidation .it’s also an useful vascular dilatation material. PGI2 and TXA2 are totally different in f更多还原