【作者】 蔡宝祥；

【导师】 谢梅林； 顾振纶；

【作者基本信息】 苏州大学 ， 药理学， 2004， 硕士

【摘要】 目的：研究消瘀片调脂有效部位群对血脂影响的交互作用，以及该部位群稳定动脉粥样硬化斑块的作用及其机制。 方法：通过聚酰胺柱层析和溶剂萃取法分离丹参和山楂各部位提取物。采用高脂血症小鼠模型，观察丹参和山楂各部位提取物经正交设计后的组方对血脂的影响。建立可诱发动脉粥样斑块破裂的家兔模型，运用图像分析方法观察该部位群对粥样斑块破裂处血栓形成面积的影响，利用光镜和电镜观察破裂斑块的形态学特征，用比色法动态观察血脂和血浆脂蛋白水平，用比浊法检测血小板聚集性，用旋转血液粘度计检测血液流变学指标，用放免法检测主动脉壁组织6-keto-PGF_1α、TXB₂含量及其比值的变化，免疫组化法检测Bax蛋白和原位杂交法检测MMP-2 mRNA表达的变化。 结果：（1） 从丹参水溶性总酚提取物中得到具有邻二酚羟基的75％乙醇提取物和具有非邻二酚羟基的氨水提取物，从山楂总三萜酸提取物中得到具有低极性的山楂石油醚提取物、中极性的山楂丙酮提取物和高极性的山楂无水乙醇提取物。（2） 丹参提取物和山楂丙酮提取物合用，可协同降低高脂血症小鼠血清TC、LDL-C，丹参提取物和山楂无水乙醇提取物合用，可协同升高高脂血症小鼠血清HDL-C。（3） 消瘀片调脂有效部位群可明显抑制粥样斑块破裂处血栓的形成，且大剂量效果更明显。同时也可抑制斑块中泡沫细胞的形成和聚集，使纤维帽尤其是肩部区的结构保持得较为完整。（4） 消瘀片调脂有效部位群可明显降低粥样斑块破裂兔的血清TC、TG、LDL-C水平，使粥样斑块血管壁中的胆固醇含量降低。（5） 消瘀片调脂有效部位群可通过降低腹主动脉TXB₂含量，和升高胸主动脉6-keto-PGF_1α含量使6-keto-PGF_1α／TXB₂的比值明显增加。该部位群也可明显抑制粥样斑块破裂兔的血小板聚集，可使粥样斑块破裂兔全血粘度、血浆粘度和红细胞聚集性明显降低，以大剂量较为明显。（6） 消瘀片调脂有效部位群治疗后，血管壁组织中Bax蛋白和MMP-2 mRNA表达的阳性细胞数减少。消淤片调脂有效部位群分离、交互作用及稳定动脉粥样斑块作用t)l制研究中文摘要结论:消癖片中的各调脂有效部位间存在着对调脂有益的交互作用，该部位群具有一定的稳定动脉粥样硬化斑块的作用，其机制可能与调节血脂、抑制粥样斑块中胆固醇聚集、液流变性、调节血管壁6一keto一PGF:。和TxB:含量及其比值、改善血小板聚集性和血抑制Bax蛋白和MMP一2 mR-NA更多还原

【Abstract】 Objective: To investigate interactions of effective :;ite clusters separated from xiaoyu tablet on blood lipid-regulation, and observe protection of the site clusters on vulnerable atherosclerotic plaque and study its possible mechanis ns.Methods: Each site of Danshen and Shanzha exfacts was separated by polyamide-column chromatography and solvent extraction, respectively. The interactions of effective site clusters on blood lipid of hyperlipidemic trice were observed by orthogonal experimental design. A rabbit model of unstable atherosclerotic plaque which could be evoked into rupture was created. Effect of xiaoyu tablet ,consisted of effective site clusters ,on vulnerable atherosclerotic plaque was observed. Area of thrombosis on atherosclerotic aorta, morphologic character of plaque rupture, levels of blood lipid and lipoprotein, platelet aggregation and indexes of hemorheology, contents of 6-keto-PGF1α and TXB2 and their ratio in aorta, expressions of Bax protein and MMP-2 mRNA in aorta were determined by image analysis , electron and light microscope, chromatometry, turbidimetry, radioimmunoassay, immunohistochemistry, hybridization in situ, respectively.Results: (1) 75% ethanol site and ammonia site were separated from Danshen total phenol acid extract, Shanzha petroleum ether site,Shanzha acetone site and Shanzha anhydrous alcohol site were isolated from Shanzha total triterpenic acid extract (2) Danshen extract and Shanzha acetone extract were able to decrease the levels of serum TC and LDL-C synergically. Danshen extract and Shanzha absolute alcohol extract were able to increase the level of serum HDL-C synergically. (3)Xiaoyu tablet obviously inhibited thrombosis on atherosclerotic plaque and foam cell formation and aggregation in plaque, kept integrity of fiber cap and shoulder area. (4) Xiaoy a tablet down-regulated serum TC,TG and LDL-C in atherosclerotic rabbits, and reduced cholesterol content in abdominal aorta. (5)Xiaoyu tablet inhibited platelet aggregati 3n, especially at dose of 169 mg/kg. It increased the ratio of 6-keto-PGF1α/TXB2 in aorta of atherosclerotic rabbits. Xiaoyu tablet reduced blood viscidity , plasm viscidity, AIRC in atherosclerotic rabbits. (6) Xiaoyu tablet decreased positive cell expressions of Bax protein and MMP-2 mRNA inatherosclerotic aorta.Conclusions: Effective site clusters separated from xiaoyu tablet were able to regulate the levels of blood lipid synergically, and increase stability of atherosclerotic plaque of abdominal aorta in rabbits as well. The latter effect was associated with regulation of blood lipid , 6-keto-PGFi ?,TXB2 and their ratio in aorta, inhibition of platelet aggregation, reduction of blood viscidity and plasm viscidity, arid inhibition of Bax protein andMMP-2 mRNA expressions.更多还原