【作者】 任梓华；

【导师】 李连达；

【作者基本信息】 浙江大学 ， 中药学， 2009， 硕士

【摘要】 缺血性心脏病是严重危害人类健康的疾病之一。丹参酮ⅡA（TanⅡA）是活血化瘀中药丹参的主要脂溶性活性成分之一,近年来已有报道证明TanⅡA对心血管疾病有很好的治疗效果,但其对心肌梗死后炎症反应的作用,及其保护机制的研究仍然比较缺乏。本实验旨在研究TanⅡA是否对大鼠心肌梗死后的炎症反应有干预作用,并探讨其可能的作用机制。本实验分为两个部分,第一部分从整体动物水平研究TanⅡA对大鼠心肌梗死后病理变化及炎症反应的作用。方法:实验采用永久性冠状动脉结扎法（LAD）造模,动物分为模型组,药物治疗组和假手术组,造模后1周采集血流动力学数据并取材,进行血清生化指标,病理切片,基因及蛋白水平的研究;结果:TanⅡA（60 mg/kg,灌胃给药）可显著改善梗死后的心脏功能,减少梗死面积及胶原沉积;分子水平的研究表明TanⅡA可以显著减少炎症相关基因MCP-1、TGF-β₁、TNF-α的表达以及其蛋白表达,同时还能够减少核因子NF-κB在细胞核中的表达。结论:TanⅡA对大鼠心肌梗死损伤有很好的保护作用,该作用与其对炎症因子MCP-1、TGF-β₁、TNF-α以及核因子NF-κB的抑制作用相关。第二部分从细胞水平研究TanⅡA的抗炎作用机制。方法:分别培养SD大鼠乳鼠原代心肌细胞和成纤维细胞,采用TNF-α刺激造模,并在造模24小时后测定细胞上清及细胞中炎症相关蛋白表达。Transwell法检测MCP-1诱导的人单核细胞（THP-1）的趋化实验。结果:TanⅡA可以抑制大鼠心脏成纤维细胞的MCP-1、TGF-β₁的表达,且呈剂量依赖性抑制作用。同时TanⅡA还可以提高心肌细胞表达TGF-β₁,但对心肌细胞表达MCP-1无明显改善作用。TanⅡA对MCP-1诱导的单核细胞趋化性无明显抑制作用。结论:TanⅡA可以减轻由TNF-α引起的炎症因子MCP-1的表达,同时可以通过调节TGF-β₁保护心肌细胞,减轻纤维化。虽然TanⅡA对MCP-1诱导的单核细胞趋化性没有明显抑制作用,但能够降低单核细胞的活性,从而缓解心肌梗死后的炎症损伤。更多还原

【Abstract】 Ischemic heart disease is a serious illness harmful to human health.Danshen is a commonly used traditional Chinese medicine for the treatment of cardiovascular diseases.Tanshinone IIA（Tan IIA）,as a key compound of Danshen,has been proved to protect the cardiovascular diseases.But the report of Tan IIA to treat myocardium infarction is rare.Present study was performed to investigate whether Tan IIA,which has shown cardio protective capacity on myocardial ischemia,has the effects of inhibiting the inflammatory responses following myocardial infarction and its potential mechanisms.This experiment contains two parts.The first part was to measure the cardio-protect effects of Tan IIA in vivo.Method:Rat myocardial infarction（MI） model was induced by permanent left anterior descending coronary artery（LAD） ligation.After the operation rats were divided into three groups（sham,MI and Tan IIA）.One week later,haemodynamics data were determined,and then rats were killed to collect the samples for serum biochemical analysis,pathology analysis,gene and protein analysis.Result:Administration of MI rats with Tan IIA（60 mg/kg/d） attenuated the MI pathological changes and improved the heart function,reduced expression of MCP-1,TGF-β₁ and macrophage infiltration in infracted border zone of myocardium.Furthermore,Tan IIA could also decrease the expression of TNF-αand activation of NF-κB.Conclusion:Tan IIA could markedly reduce myocardial infarction induced myocardium injury.This may be attribute to its inhibiting effects on MCP-1、TGF-β₁、TNF-αand NF-κB.The second part was to measure the cardio-protect effects of Tan IIA in vitro. Method:Inflammatory model was established by TNF-αstimuli on cardiacmyocyte and cardiac fibroblast.MCP-1 induced monocyte chemotaxis was measured by using a transwell plate.Then,the effect of TanII A on inflammation and chemotaxis were analyzed.Result:Tan IIA could reduce MCP-1 and TGF-bbbbbb₁ secretion of cardiac fibroblasts in a dose dependent manner,and could increase TGF-bbbbbb₁ secretion in cardiacmyocyte.But Tan IIA can’t significantly inhibit MCP-1 induced transmigration of THP-1 cells.Conclusion:Tan IIA could reduce TNF-aaaaaaaaaa induced MCP-1 expression, protect cardiacmyocyte and reduce fibrosis.Though Tan IIA can’t significantly inhibit MCP-1 induced transmigration of THP-1 cells,it can decrease the activity of THP-1 cell.更多还原