【作者】 张萌；

【导师】 张伯礼； 高秀梅；

【作者基本信息】 天津中医学院 ， 中医内科学， 2005， 博士

【摘要】 目的 丹参、三七是复方丹参方的主要组成,以往研究表明其抗心肌梗死存在最佳配比范围。在前期工作的基础上,本研究探讨丹参的主要水溶性成分丹酚酸B(Sal B)与三七的主要成分三七总皂苷(PNS)单用和配伍对实验性大鼠心肌梗死及心脏基因表达谱的影响,对心肌梗死后心肌细胞凋亡的抑制作用及分子机制,为中药组分配伍研究模式提供科学依据。 方法 结扎冠脉左前降支复制大鼠心肌梗死模型,假手术组作对照,连续灌胃给药7天。 1.称量左心室、左心室梗死区心肌组织重量,计算心肌梗死范围;放射免疫法测定血浆Ang Ⅱ释放水平: 2.用生理记录仪检测血流动力学指标变化; 3.用彩色超声心动仪观察心脏左室结构和功能变化; 4.采用Affymetrix基因芯片观察大鼠心脏梗死边缘区基因表达谱变化; 5.采用流式细胞术Annexin V-FITC/PI法检测大鼠心脏梗死边缘区心肌细胞凋亡情况; 6.应用实时荧光定量RT-PCR技术检测与心肌细胞凋亡及调控通路相关基因表达情况。 结果 1.与模型组相比,Sal B、PNS以及各配伍组可以不同程度地降低心肌梗死范围,有降低血浆Ang Ⅱ释放水平的趋势,配伍高剂量组有优于其它中药组的趋势。 2.Sal B、PNS以及各配伍组均可以不同程度地降低心电图ST段波幅、血清LDH释放水平、左室舒张内压(LVDP),升高左室内压最大上升和下降速率(+dp/dtmax、-dp/dtmax),配伍组对上述指标的作用有优于单独用药组的趋势。 3.Sal B、PNS以及各配伍组可以不同程度地降低左室收缩末期内径(LVDs)、左室收缩末期后壁厚度(LVPWs)、左室收缩末期容积(LVESV),升高左室射血更多还原

【Abstract】 Background and ObjectiveSalvia miltiorrhiza Bunge and Panax notoginseng are major ingredients of the Compund Danshen Formula. Previous researches have proved that there exists the best ratio when these two herbs are used in combination. Salvianolic acid B (Sal B) and panax notoginseng saponins (PNS) are major components isolated from them respectively. In order to search for the molecule mechanism of Sal B and PNS against myocardial infarctiom and elucidate the scientific connotation of compatibility in TCM formulas, we observed the effects of Sal B and PNS used alone and in combination on rats with acute myocardial infarction. MethodsWe produced myocardial infarction in anaesthetized rats by occluding the left descending coronary artery. Sham-operated rats served as controls. Rats were randomly divided into eight groups and treated with angiotensin converting enzyme inhibitor (ACEI) captopril, Sal B, PNS and the combination of Sal B and PNS. Control and model received saline only.1. In order to measure the infarcted area, we assayed the weight of the left ventricular and left ventricular infracted tissue. The plasma contention of Ang II was also assayed.2. We observed the effects of Sal B and PNS used alone and in combination on hemodynamic in rats.3 . We assayed the construction and function of left ventricular by using echocardiography.4. We observed gene expression changes in the areas near the infarcted tissue using the Affymetrix GeneChip Arrays.5. The number of apoptotic myocytes was determined using Annexin V-FITC/Pi by flow cytometry.6. By using real-time RT-PCR, we assayed the mRNA expression of myocardialapoptosis related genes. Results1. Sal B, PNS and the combination of Sal B and PNS can decrease the infarcted areas and the plasma content of Ang II compared with model. There was a trend that the effects of high dose group of the combination of Sal B and PNS were better than others.2. Sal B, PNS and the combination of Sal B and PNS can decrease the elevation of ST-segment. Sal B and PNS also can reduce the release of LDH, decrease the left ventricular diastolic pressure (LVDP), and increase +dp/dtmax and -dp/dtmax. There was a trend that the effects of Sal B and PNS used in combination were better than alone.3. Sal B, PNS and the combination of Sal B and PNS can decrease LVDs, LVPWs, LVESV and increase EF and FS. There was a trend that the effects of middle dose group of the combination of Sal B and PNS were better than others.4. Of the genes on the arrays, there were 22% genes in the model group changed in expression level relative to the control, 11% genes were differentially expressed in higher level and another 11% genes were in lower level. The genes displayed a minimum of twofold change in expression level include clotting system regulators, left ventricular remodeling genes, immune response-related genes, energy metabolism regulators, inflammatory factors, signal transducing molecules.There were 5.7% genes in Sal B group changed and 0.3% displayed a minimum of twofold change in expression level over the model group. There were 5.7% genes in PNS group changed and 0.8% displayed a minimum of twofold change in expression level over the model group. There were 14% genes changed in Sal B and PNS group and 3% displayed a minimum of twofold change, in expression level over the model group. The genes differently expressed in Sal B and PNS group were more than the groups used alone.5. All the treated groups can limit the percent of myocardial apoptosis and the effect of the combination is the most significant.更多还原