益气化痰活血法对SHR心肌重构及相关原癌基因表达的影响

【作者】 唐咸玉；

【导师】 邓中炎；

【作者基本信息】 广州中医药大学 ， 中医基础理论， 2001， 硕士

【摘要】 左心室肥厚（Left ventricular hypertrophy,LVH）是高血压病（essentialhypertension，EH）的主要并发症之一，近年来被认为是一种独立的心血管疾病危险因素，其病理改变主要是心肌细胞肥大和间质纤维化。血流动力学、神经、体液及内分泌因素参与了LVH的发生与发展。近年来人们发现，许多心血管疾病与原癌基因有着密切关系，LVH是心肌及其间质细胞对生长因子的一种应答反应。心脏负荷增加，促进癌基因myc和fos以及ras的异常表达，进而促进细胞的增殖和肥大，因而心肌肥厚可能是某些癌基因激活的最终结果。 心肌病理性肥厚，引起心室舒张期硬度增加，顺应性减退，首先出现舒张功能障碍，进而影响收缩功能，最终导致心力衰竭。胶原纤维合成增加，心肌纤维化，造成间质网络结构破坏；并能使心肌组织电的各向异性增加，容易引起心律失常，甚至猝死。治疗高血压病，不仅要把血压降至正常范围，更重要的是要减少因高血压引起的猝死、心律失常、心肌梗塞和其他心血管病的危险性，逆转心肌肥厚，提高生活质量。目前的西医学治疗在控制血压和降低左室重量方面疗效较好，但在逆转心肌间质纤维化、改善心功能等方面疗效不尽人意。 高血压病以中老年人居多，且多有病程长、反复发作、迁延难愈的特点，左室肥厚属有形改变，从宏观上把握是痰瘀为患。归纳高血压左室肥厚患者的临床表现，结合中医基础理论，本课题组认为左室肥厚为痰瘀阻于心，正虚和邪实并存，正虚是指气虚，邪实为痰浊、瘀血阻滞。故将益气化痰活血作为治疗LVH的主要治法，并制成纯中药复方制剂——心肌康，用于防治LVH，在既往的临床研究中取得良好疗效，并且可以较好地改善患者的生活质量。 为从理论上进一步阐明中医益气化痰活血法逆转EH-LVH的作用机理，本研究从形态学、心肌超微结构及分子机制等方面，观察对比了自发性高血压大鼠（SHR）在益气化痰活血复方治疗前后的尾动脉收缩压（SBP）、左室重（LVW）、左室重/体重（LVW/BW）、心肌细胞线粒体 毕业论文比表面（6S以及大鼠左心室心肌N《SS fllRNA表达水平的变化。结果发现：益气化痰活血复方可降低SHR大鼠的尾动脉收缩压、降低左室重量，增加心肌细胞线粒体比表面（5 s卜 并能抑制肥厚左室 N－ras原癌基因的表达，部分地说明了益气化痰活血法治法逆转LVH的机理。更多还原

【Abstract】 Effect of treatment of the thcrapic principle (invigorating Qi, removing the phlegm and promoting blood circulation )on the remodeling of myocardium and the expression of proto-oncegene in spontaneously hypertensive ratsLeft ventricular hypertrophy(LVH) was one of the main complications of essential hypertension(EH), and was considered as an independent cardiovascular dangerous factor in these years. The tissue of left ventricular remodeled, comprising the hypertrophy of cardiomyocyte and the fibrosis of interstitial of heart. Blood stream dynamics, nerve factors, body fluid factors, and internal secretion factors have been involved in the occurrence and development of essential hypertension with LVH. During these years more and more scholars have found that cardiovascular diseases are connected with proto-oncogene closely. LVH was considered as the responsive reaction of cardiomyocyte and the interstitial cells of heart to the growth factors. With the aggravation of the burden of heart, the expression of cellular proto-oncogene c-myc, c-fos and ras were enhanced abnormally, which made cardiomyocytes multiply and hypertrophic. And LVH might be the finally result of some proto-oncogenes which had been activated.With the development of hypertrophy of left ventricular, the diastolic stiffness increased and the left ventricular compliance decreased. This could make the ventricular function lower, and the symptom of heart failure would be found lastly. The abnormal accumulation of interstitial collagen and myocardial fibrosis could destroy the network structure of myocardial interstitium. So the probability of the occurrence of arrhythmia and sudden death would be arising sigr~ificantly. To treat the EH, it is not only lowering the blood pressure to ordinary range, but also reducing the dangerous factors which were arisen by EH-LVI-I, such as sudden death, arrhythmia, myocardial infarction, and so on. The result was reversing the cardiac hypertrophy and improving life quantity. The current therapy of western medicine was fairlygood at lowering blood pressure and left ventricular mass index, but not quite good at recovering the course of fibrosis to improve heart function.It could be discovered that most of the patients of EH-LVH were middleaged and the course of the disease was long as well as the disease was often recrudesced. In accordance with the clinical symptoms and basic theory of TCM, we think LVH was caused by the accumulation of phlegm and blood stasis in the heart. Both excess syndrome and deficiency syndrome were the two sides of the disease. So combination of strengthening the body resistance with removing pathogenic factors which can be applied to syndromes of deficient vital-Qi with excessive pathogenic factors. Such therapic principles as invigorating Qi, removing the phlegm and promoting blood circulation were adopted. XingJiKang(XJK)pill was made for the patients with EH-LVH, the clinical study previously indicated that XJK had particularly curative effect , and could improve the life quality.The further experiment ~vas made and spontaneously hypertensive rat(SHR)was used, systolic blood pressure was measured by tail-cuff method .LVH was defined according to the ratio of left ventricular weight to body weight. Specific surface of myocardial mitochondria membrane was evaluated by the result of electron microscope. The expression of cellular proto-oncogene N-ras was calculated by PCR. Conclusions showed that the traditional Chinese medicine could reduce the systolic blood pressure(SBP), left ventricular weight(LVW) of SHR, and increase specific surface of myocardial mitochondria membrane( 6 s), it also could restrain the enhanced expression of cellular proto-oncogene N-ras in hypertrophy myocardiocyte.更多还原