节点文献
活血镇心法逆转高血压左室肥厚理论及作用机制初探
【作者】 罗斯琼；
【导师】 王亚红；
【作者基本信息】 北京中医药大学 ， 中医临床， 2008， 硕士
【摘要】 1研究背景左室肥厚(Left Ventricular Hypertrophy ,LVH)是高血压病最常见的并发症之一,它的发生与发展不仅与血流动力学因素有关,神经、内分泌等因素也起着重要的作用。Framingham心脏研究中大量的长期随访结果提示,高血压病并发左室肥厚者发生猝死、心肌梗死的危险性明显增高,Devereux多年随访表明伴有左室肥厚患者生存率显著下降。目前,高血压左室肥厚已经被列为心血管疾病的独立危险因子,因此探讨左室肥厚的发生机制、寻找合理的防治措施具有重要的理论及实践意义。近年来,已有越来越多的证据表明:心脏局部肾素-血管紧张素在高血压左室肥厚的发生、发展中具有重要的病理意义。现已证实,循环血中和/或心肌局部血管紧张素Ⅱ(AngiotensinⅡ,AngⅡ)是引起心肌细胞肥大的最重要活性物质,该作用可被血管紧张素受体亚型1拮抗剂所阻断。中医虽无高血压病左室肥厚的疾病诊断,但中医基础和应用基础理论对于人体健康的躯体和高血压病时的心肌肥厚一系列改变的基本认识是人体内的阴阳平衡与失衡。人体健康的躯体是以阴阳依存互根为基础的,即“阳生阴长”、“阴在内,阳之守也”、“阳在外,阴之使也”,高血压病的一系列表现使体内的阴阳失衡,高血压左室肥厚是高血压病在新状态下建立起的相对的“阴阳平衡”,这种相对的平衡是机体在前一阴阳失调后代偿的结果。中医对于左室肥厚的临床证型所见主要表现在血瘀、气虚和肝肾阴虚。治疗以活血、益气、补肾、平肝和滋阴为主要原则,应用有关药物取得一定的临床疗效。2研究目的通过总结近十五年的国内外文献中关于AngⅡ致心肌细胞肥大及相关信号通路的研究成果,研究活血镇心法逆转高血压左室肥厚作用机制,并通过预实验探讨该研究方向的可行性,为进一步研究做前期条件摸索。3研究方法文献综述方面以“左室肥厚”、“信号转导”、“心肌细胞”为关键词查找CNKI数据库,筛选出近15年的相关文献,以“Left Ventricular Hypertrophy”及“Signal transduction pathway”为第一关键词以“AngiotensinⅡ”为第二关键词搭配搜索Pubmed中相关文献。中医方面从病名、病机、证型及治疗角度进行总结,探讨以活血镇心法立方的降压通脉方治疗高血压左室肥厚的中医理论。西医方面从信号转导角度入手,总结和左室肥厚相关的信号通路蛋白,并从中寻找现有研究报道中已知和左室肥厚关系较为密切但研究相对较少的信号通路蛋白,并以此为突破点进行相关实验研究。实验研究方面通过对原代培养心肌细胞加入AngⅡ造模,再给予西药及降压通脉方干预,采用考马斯亮兰法比较空白组、模型组、西药组、中药组之间总蛋白含量差异,并以此选择出最佳的药物作用浓度点。4研究结论(1)高血压左室肥厚的产生与神经内分泌因素密切相关,神经内分泌刺激信号,主要通过PKC和MAPK两条信号通路使蛋白质合成增加、细胞体积增大、间质胶原合成增加,从而出现LVH。(2)高血压和高血压左室肥厚的中医辨证论治存在同一性,而血瘀证是贯穿整个发病过程的病理机制。(3)活血中药丹参、川芎等及其有效成分可抑制AngⅡ引起的心肌细胞肥大。(4) AngⅡ对培养的乳鼠心肌细胞有明显的促肥大的作用。(5)高浓度的降压通脉方有心肌细胞毒性。(6)降压通脉方可以抑制AngⅡ诱导的心肌细胞肥大,其原理可能与抑制PKC和MAPK信号通路蛋白表达相关。
【Abstract】 BackgroundLeft Ventricular Hypertrophy (LVH)is one of the most commoncomplications of hypertension.It is not only the occurrence anddevelopment of the relevant factors and hemodynamic, neurological,endocrine, and other factors also play an important role. In theFramingham Heart Study, a large number of long-term follow-up resultssuggest that hypertensive patients with left ventricular hypertrophyin sudden death, the risk of myocardial infarction increasedsignificantly, Devereux years of follow-up showed that the survival ratein patients with left ventricular hypertrophy associated with asignificant drop.LVH is an independent risk factor of cardiovasculardiseases now.It is important to discover mechanisms of LVH and to findpreventive measures,which have significance in the field of boththeoretic studies and clinical practice.Morerencently,rennin-angiotensin system (RAS) activation has beenunderstood to be a major inducer of cardiac tissue hypertrophy.It hasbeen demonstrated that the local cardiac tissue hypertrophy.It has beendemonstrated that the local cardiac angiotensinⅡ(AngⅡ) is a potentgrowth factor in LVH,which can bbe blocked by AT1 receptor antagonists.There is no LVH of hypertension in Chinese medicine,but the basicknowledges of a series of changes of LVH of hypertension and body ofhuman health are balance and imbalance of yin and yang in human bodybased on basic theory of Chinese medicine.The body of human health isbased on the yin and yang interdependence for each other,such as yinwanes,yang waxes,and vice versa.A series of complications ofhypertension result from imbalance of yin and yang,while LVH ofhypertension is formed new relative balance under new circumstances.Therelative balance is the compensated results of preceding imbalance ofyin and yang.The pathologic basis of LVH os blood stasis,qi deficiencyand yin insufficiency of liver and kedney.The treatments of drugs arepromoting blood circulation,reinforcing qi,replenishingkidney,tonifying liver and nourishing yin.Such treatments get someclinic improvement of patients.Objectives By summing up the past 15 years of literature on the angiotensinⅡinduced myocardial hypertrophy and related signaling pathway,themechanism,about method of invigorating the circulation of blood andcalming heart to kickback hypertension LVH,could be researched.Andthrough pre-experimental of the feasibility study,pre-conditions toprepare for further study.Methods“Left ventricular hypertrophy”,“signal transduction”and“myocardial cells”as literature Review keywords, the relevantliteratures are selected from CNKI database.“Left VentricularHypertrophy”,“Signal transduction pathway”for the first Key wordsand“AngiotensinⅡ”as the second search Pubmed to find relatedliterature. Summing up causes of disease, pathogenesis, syndrome typeand Treatment, TCM theory on the method of invigorating the circulationof blood and calming heart medication hypertension LVH is perspective.Western medicine from the perspective of signal transduction startsumming up signaling protein associated with LVH and to look for thoseknown existing and more close to LVH but research few, as well as thebreakthrough of experimental study.The first step of experimental research is adding angiotensinⅡto the original cultured myocardial cells and giving western or chinesemedicine to intervention.Then Second is to detect the difference intotal protein content of blank group,model group,the WM group, Chinesemedicine groups by Coomassie Brilliant Comparison.At last to select theoptimal drug concentration points.Conclusions(1) The formation of hypertension left ventricular hypertrophy isclosely related neuroendocrine factors.The stimulation signals, mainlythrough PKC and MAPK signaling pathway , increase protein synthesis ,cell volume and mesenchymal collagen synthesis which have LVH.(2) Hypertension and hypertension left ventricular hypertrophy TCMDifferential Treatment existence identity, and blood stasis isthroughout the whole course of the pathological mechanism.(3) Invigorating the circulation of blood Chinese drug danshen,Chuanxiong, and other components and can inhibit AngⅡcaused myocardialhypertrophy. (4) AngⅡon cultured neonatal rat cardiomyocytes cells significantly promote the role of mast.(5) High concentrations of Jiangya Tongmai Decoction have myocardial cytotoxicity.(6) Jiangya Tongmai Decoction can inhibit the AngⅡ-induced myocardial hypertrophy, and its principles may inhibit PKC and MAPK signaling protein expression.