【作者】 宋春华；

【导师】 隋殿军；

【作者基本信息】 长春中医药大学 ， 中医内科学， 2008， 博士

【摘要】 目的:利用生理学、生物化学、病理形态学及分子生物学等技术,探讨三七苦碟子提取物抗心肌缺血的作用及其机制。方法:健康雄性Wistar大鼠分成空白组、模型组、SK治疗组(灌服三七和苦碟子提取物自制剂)高、中、低剂量组、阳性对照组(灌服复方丹参滴丸);采用异丙肾上腺素一次性多点皮下注射,复制大鼠心肌缺血动物模型。通过生理(心电图)及生化法(血清酶学),观测三七苦碟子提取物抗心肌缺血的作用。运用光镜、电镜,观察三七苦碟子提取物对缺血大鼠心肌损伤及细胞凋亡的影响,并运用免疫组化、蛋白印记法观察其对细胞凋亡相关基因Bcl-2、Caspase-3蛋白表达的影响研究,探讨三七苦碟子提取物抗心肌缺血作用的机制。结果:1.三七苦碟子提取物对急性心肌缺血大鼠的心电图S-T段、血清磷酸肌酸激酶(CK)、磷酸肌酸激酶同功酶(CK-MB)相关指标均有较好的调节效果,且呈量效依赖关系,其中尤以SK高、中剂量组为显著,其总体作用优于阳性对照组(复方丹参滴丸)。2.在研究中,我们发现三七苦碟子提取物能够显著降低急性心肌缺血大鼠血清CK、CK-MB水平,提示三七苦碟子提取物可使血管扩张,减轻心肌缺血损伤。3.在研究中,我们发现三七苦碟子提取物能使急性心肌缺血大鼠受损心肌组织的显微结构和超微结构明显得到改善,其中尤以SK高、中剂量组为显著,其总体作用优于阳性对照组(复方丹参滴丸)。提示三七苦碟子提取物可减轻心肌缺血损伤,对心肌细胞有保护作用。4.三七苦碟子提取物能分别增加和抑制Bcl-2、Caspase-3基因的蛋白表达,抑制和阻断急性心肌缺血大鼠心肌细胞过度凋亡的发生,其高、中剂量组的作用均优于阳性对照组(复方丹参滴丸)。结论:三七苦碟子提取物能有效的抗大鼠急性心肌缺血。其作用机制可能与降低急性心肌缺血大鼠血清CK、CK-MB水平、抑制心肌细胞凋亡,以及调节心肌Bcl-2、Caspase-3等凋亡相关蛋白表达密切相关,通过多种综合的作用机制起到保护心肌细胞、抗急性心肌缺血损伤的作用。更多还原

【Abstract】 Background:Extract fromlxeris of Panax notoginseng and Ixeris sonchifolia-hance (SK) is an effective durg that be summed up by my tutor.The principle of supplementing qi and activating blood is the therapeutiec prineiple Which treating CHD(coronary heart disease) of asthenic qi and blood stasis.In this treatise,through animal experiments studies,we can see themechanisms of how Extract SK can play an influential role in prevention and treatment of CHD can be deeply probed into.objectives:To observe the effect of traditional Chinese medieinal herb(SK) on acute myocardial ischemia modle rats,and to approach the action and mechanism of preventing coronary heart disease(CHD).Method:Using modern scientific technology to study SK,including pharmacy, pharmacology and phathology.Using danshendiwan positive control and acute myocardial ischemia modle rats as study object,we can observe the effect of different concentration SK on ECG,and BL00D VISCOSITY,CK,CK-MB,as well the adjustment of Bcl-2,Caspase-3 gene and apoptosis by test methods such as enzyme assay,opties microscope,electric microscope,morphologic nitrate reduction,immunohisto-chemical method,western bioting.Results:1 SK has obvious dose-dependent decrease effect on model rats S-T segment deviation, CK,CK-MB,and the effect is better than danshendiwan when middle and high dosage.2 The studies show that SK infusion manifest the anti-damage function to acute myocardial ischemia;SK has obvious regulation effect on model rats;it can debase CK, CK-MB.3 The studies show that SK infusion manifest the anti-damage function to acute myocardial ischemia and can protect cardiac muscle cell;SK has obvious improvement effect to micro-structure of showing and ultra micro-structure on model rats;it can debase cardiac muscle organize.and the effect is better than Danshendiwan when middle and high dosage.4 SK infusion may increase or disrupt the porceduer of cell apoptosis by regulating the expression of Bcl-2 gene and Caspase-3 gene,depress or disrupt the over-apoptosis procedure of acute myocardial cells,and the effect is better than Danshendiwan when middle and high dosage.Conclusions:SK have effective anti-myocadrial ischemia function.The mechanism probably relate to inhibiting CK,CK-MB secretion,and depress or disrupt the procedure of cell apoptosis by regulating the expression of Caspase-3 and Bcl-2 gene.The search results shown above suggest that SK can protect cardiac muscle cell and play a significant anti-damage role to myocardial ischemia thorugh a mlltiplechannelled synthetically mechanism.更多还原