芪参还五胶囊对冠心病大鼠hs-CRP、TNF-α的影响

发布时间：2018-01-19 02:27

本文关键词： 冠心病动脉粥样硬化芪参还五胶囊 SD大鼠炎性因子　出处：《河北医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的:通过建立冠心病大鼠模型,观察不同剂量芪参还五胶囊对于冠心病大鼠动脉血清中hs-CRP和TNF-α的水平影响及改善心肌缺血的作用。冠心病(CHD)是动脉粥样硬化病变引发器官病变最严重也是最常见的类型,其主要是因冠脉粥样硬化和(或)因冠脉功能性改变导致冠脉狭窄或梗塞,进而引起心肌缺血、缺氧甚至坏死[1,2]。其形成原因早年认为是冠脉血管退行性变及管道问题,近些年研究则发现炎症反应在冠心病的发生发展中起到重要作用,因此对于冠心病的预防及治疗已由最初的降低血清血脂水平、减少危险因素等手段,转变为控制炎性反应减少炎性因子的合成及分泌,CRP在炎症反应急性时相由肝脏合成并分泌,可以反应全身炎症程度。身体的感染与损伤会引起血清CRP浓度急剧升高,且感染程度与升高幅度成正比,控制感染后体内CRP水平迅速回落。CRP在AS的发生发展及相互关系中发挥重要作用。更重要的是众多炎性因子中CRP(C反应蛋白)是可以独立预测冠心病及血管损伤严重程度的因子,因而逐渐引起临床及科研工作者重视,通过降低身体内CRP水平不仅可以抑制炎症的进展也可以起到预防动脉粥样硬化的作用。TNF-α(Tumor necrosis factor--α)即肿瘤坏死因子α,主要由巨噬细胞分泌,其他可以分泌TNF-α还有血管内皮细胞、单核细胞等,除可杀伤并抑制肿瘤细胞外,还可促进局部炎症反应,并诱导相关细胞因子的产生,进而在机体细胞的功能调节、炎症反应和免疫等方面发挥重要作用,对于心血管系统,TNF-α可以诱发心肌细胞凋亡并降低心肌收缩力。TNF-α在AS形成的过程中发挥了重要作用,能增强动脉粥样硬化斑块中巨噬细胞的吞噬作用并诱导释放大量炎性因子,进而可以损伤血管内皮,激活内源性凝血途径,并增加血管通透性,导致局部血栓形成,参与AS的形成。心肌细胞在缺血、缺氧、病毒感染情况下可表达并分泌TNF-α。而过度表达的TNF-α反过来又可损伤心肌,加重心功能不全。相关研究发现,降低大鼠体内TNF-α水平可以改善大鼠心功能。因此本实验中选用TNF-α作为观测心脏损伤的指标,具有重要的临床及科研意义。芪参还五胶囊是河北省沧州中西医结合医院自主研发并生产的中成药,该药既吸取了传统中医对冠心病病机的研究,又兼顾现代中药研究成果,在补阳还五汤的基础上加用全虫等组分。现代研究表明黄芪能提高机体清除自由基及抗脂质过氧化的能力,进而增强机体抗氧化的能力,同时可降低血小板的粘附性及抑制血栓形成,故可以用于冠心病的预防及治疗。水蛭、地龙可减轻心肌组织的炎症反应,改善血液循环,有利于心肌功能的恢复,与黄芪合用可增强抗血小板预防血栓形成的功能,并可以改善局部及全身血液循环状态。本实验中,通过饲喂高脂饮食及注射垂体后叶素模拟冠心病发生发展的自然病程制作大鼠冠心病模型,然后应用芪参还五胶囊生药灌胃,之后监测炎性指标并观察心脏心肌及冠脉的病理变化,揭示中药治疗冠心病的原理,为中药治疗冠心病提供新的理论依据。实验方法:1雄性SD大鼠共56只随机分成2组,分别为空白组13只、造模组43只,空白组给予普通大鼠维持饲料饲喂,造模组大鼠给予高脂饲料饲喂8周以造成血脂异常模型,8周后饲造模组大鼠给予垂体后叶素30U/kg腹腔注射连续3天,以造成冠心病大鼠模型,空白组给予同等体积蒸馏水腹腔注射,禁食水24小时后空白组及造模组分别随机取抽取3只大鼠,摘取心脏,固定,进行病理切片及镜下观察。2造模组分为实验组、低剂量组、中剂量组、高剂量组,其中低中高剂量组依据体重每日分别给予芪参还五胶囊生药药物溶液灌胃一次,剂量分别为0.125g/(kg·d)、0.25g/(kg·d)、0.5g/(kg·d),空白组及实验组则依据大鼠体重每日给予生理盐水灌胃,共计28天。3灌胃结束后,禁食水24小时,以10%水合氯醛3ml/kg腹腔注射麻醉,腹主动脉取血,然后以3500r/min转速离心血液15分钟,取上层清液,冷冻保存,留备检测炎性因子等相关指标,腹主动脉注射甲醛溶液,待心肌组织变白,且大鼠四肢不自主抽搐,摘取心肌组织,以4%多聚甲醛固定,备做病理检测。统计学方法:应用SPSS21.0软件进行统计学分析。计量资料采用均数加减标准差(?)表示,两样本间用t检验,多个样本均数则采用方差分析(LSD-t),检验水准α=0.05。结果:1成功复制出大鼠冠心病、心肌缺血模型;2芪参还五胶囊可降低冠心病大鼠血清中hs-CRP、TNF-α浓度,且差异具有统计学意义。3低、中、高剂量的芪参还五胶囊对于降低大鼠血清中hs-CRP和TNF-α的效果不完全同。4芪参还五胶囊可明显改善冠脉血管内皮形态,减少缺血灶的产生,因而可证明对心肌缺血具有一定改善作用。结论:芪参还五胶囊可降低炎性因子的程度与生药剂量相关,并且通过降低炎性因子的方法,达到抗心肌缺血的目的,对于冠心病的防治具有良好作用。
[Abstract]:Objective: to establish the rat model of coronary heart disease, to observe the effects of different doses of Shenqi Capsule on myocardial ischemia was five hs-CRP and TNF- alpha in rat artery disease in serum and improve the coronary heart disease. (CHD) is the most serious disease caused by atherosclerosis in organ is the most common type, which is mainly due to coronary atherosclerosis and (or) due to changes in coronary function lead to coronary artery stenosis or infarction, then cause myocardial ischemia, hypoxia and necrosis of [1,2]. that is the causes of early coronary vascular degeneration and pipeline problems, recent studies found that inflammation in the occurrence of coronary heart disease plays an important role in the development of the prevention and treatment of coronary heart disease has been from the initial decrease of serum lipid levels, reduce the risk factors and other means to control the inflammatory reaction and decrease the synthesis and secretion of inflammatory cytokines, inflammation in CRP Acute phase reaction can be synthesized by the liver and secreted, and systemic inflammatory response. Infection and damage the body will cause a sharp increase in the concentration of serum CRP, and the degree of infection and increased the amplitude is proportional to the levels of CRP in the control of infection after the rapid decline of.CRP play an important role in the occurrence and development of AS and the relationship between the more important. Many inflammatory factors in CRP (C reactive protein) is the independent predictor of coronary heart disease and vascular injury severity factor, which has caused clinical and scientific importance, progress by reducing the level of CRP in the body can not only inhibit the inflammation can also play a role in the prevention of atherosclerosis.TNF- alpha (Tumor alpha necrosis factor--): tumor necrosis factor alpha, mainly secreted by macrophages, other secretion of TNF- and vascular endothelial cells, monocytes, in addition to killing and inhibiting tumor cells, Can also promote the local inflammatory reaction and induce cytokine production, and the function of the body cell regulation, play an important role in inflammation and immune aspects for the cardiovascular system, TNF- could play an important role in the process of myocardial cell apoptosis induced by.TNF- and decreased myocardial contractility in AS formation, can enhance phagocytosis of macrophages in atherosclerotic plaque and induced release of inflammatory cytokines, which can damage the vascular endothelium, activation of endogenous coagulation pathway and increased vascular permeability, leading to thrombus formation, involved in the formation of AS. In myocardial cells after hypoxia ischemia, and virus infection can express and secrete TNF- alpha case. Over expression of TNF- a turn can damage the myocardium and heart dysfunction. The study found that the decreased level of TNF- alpha in rats can improve cardiac function in rats. So this An experiment using TNF- alpha as observation of cardiac injury index, with clinical and scientific significance. Qishen capsule is also five independent research and development and production of Chinese patent medicine hospital of Hebei province Cangzhou traditional Chinese medicine and Western medicine, the medicine not only absorbs the research on the pathogenesis of coronary heart disease of traditional Chinese medicine and modern medicine, and lab research results, combined with scorpion components based on the positive also five soup. Modern research shows that Astragalus can improve the ability of scavenging free radicals and anti lipid peroxidation in the body, thereby enhancing the ability of antioxidation, and can reduce the adhesion of platelets and inhibit thrombosis, so it can be used for the prevention and treatment of coronary heart disease. The inflammatory reaction of leech, earthworm can relieve the myocardial tissue, improve blood circulation, is conducive to the recovery of myocardial function and Astragalus can enhance platelet thrombosis prevention function, and can improve the local and systemic blood Liquid circulation. In this experiment, by feeding high fat diet and injection of pituitrin to simulate the natural course of development of coronary heart disease in rats model with coronary heart disease, and then the application of Shenqi capsule five crude drug gavage, after the pathological changes of inflammatory markers and observe the monitoring of myocardial and coronary artery, revealing the principle of traditional Chinese medicine in the treatment of coronary heart disease and provide a new theoretical basis for Chinese medicine treatment of coronary heart disease. Methods: 1 a total of 56 male SD rats were randomly divided into 2 groups, namely control group 13, model group 43, control group was given ordinary rat feed to maintain, model group rats were given high-fat diet fed 8 weeks to create a model of blood lipid the abnormal, after 8 weeks of feeding model group rats were treated with Pituitrin 30U/kg intraperitoneal injection for 3 days, to cause coronary heart disease model rats, blank group was given equal volume of distilled water by intraperitoneal injection, fasting for 24 hours after the blank group and the model Groups were randomly selected 3 rats, removal of the heart, fixed, pathological and microscopic observation of.2 rats were divided into experimental group, low dose group, middle dose group, high dose group, high dose group and low in the basis of body weight per day were given Shenqi capsule drug drug five solution gavage a dose of 0.125g/ (kg d), 0.25g/ (kg - D), 0.5g/ (kg - D), blank control group and experimental group according to the body weight of rats received daily saline, a total of 28.3 days after gavage, fasting for 24 hours, with 10% chloral hydrate 3ml/kg intraperitoneal injection of anesthesia, blood from the abdominal aorta, and then to 3500r/min speed centrifugal blood 15 minutes, the supernatant liquid, frozen, for detection of inflammatory factors and other related indicators, abdominal aortic injection to myocardial tissue of Formaldehyde Solution, white, and rat limbs involuntary twitching, removal of myocardial tissue, fixed in 4% paraformaldehyde preparation, do pathology Test. Statistical methods: SPSS21.0 software was used for statistical analysis. Measurement data using mean and standard deviation (?), two samples with t test, multiple samples using analysis of variance (LSD-t), a =0.05. level test results: 1 successfully reproduced the rat model of myocardial ischemia of coronary heart disease, 2; five Shenqi capsule can reduce coronary heart disease in rats serum hs-CRP, TNF- concentration, and the difference was statistically significant.3 low, high dose of Shenqi capsule is five for reducing hs-CRP and TNF- alpha in serum of rats with incomplete.4 five Shenqi capsule can obviously improve the coronary vascular endothelial morphology, reduce ischemic focus, which can be proved to have certain effects on improving myocardial ischemia. Conclusion: Shenqi capsule can reduce the degree of five and inflammatory factors in crude drug dose related, and by reducing the inflammatory factor method to anti myocardial ischemia Objective, it has a good effect on the prevention and treatment of coronary heart disease.

【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R285.5

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