發(fā)布時(shí)間：2018-01-19 02:27

  本文關(guān)鍵詞： 冠心病 動(dòng)脈粥樣硬化 芪參還五膠囊 SD大鼠 炎性因子　出處：《河北醫(yī)科大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：目的:通過(guò)建立冠心病大鼠模型,觀察不同劑量芪參還五膠囊對(duì)于冠心病大鼠動(dòng)脈血清中hs-CRP和TNF-α的水平影響及改善心肌缺血的作用。冠心病(CHD)是動(dòng)脈粥樣硬化病變引發(fā)器官病變最嚴(yán)重也是最常見(jiàn)的類型,其主要是因冠脈粥樣硬化和(或)因冠脈功能性改變導(dǎo)致冠脈狹窄或梗塞,進(jìn)而引起心肌缺血、缺氧甚至壞死[1,2]。其形成原因早年認(rèn)為是冠脈血管退行性變及管道問(wèn)題,近些年研究則發(fā)現(xiàn)炎癥反應(yīng)在冠心病的發(fā)生發(fā)展中起到重要作用,因此對(duì)于冠心病的預(yù)防及治療已由最初的降低血清血脂水平、減少危險(xiǎn)因素等手段,轉(zhuǎn)變?yōu)榭刂蒲仔苑磻?yīng)減少炎性因子的合成及分泌,CRP在炎癥反應(yīng)急性時(shí)相由肝臟合成并分泌,可以反應(yīng)全身炎癥程度。身體的感染與損傷會(huì)引起血清CRP濃度急劇升高,且感染程度與升高幅度成正比,控制感染后體內(nèi)CRP水平迅速回落。CRP在AS的發(fā)生發(fā)展及相互關(guān)系中發(fā)揮重要作用。更重要的是眾多炎性因子中CRP(C反應(yīng)蛋白)是可以獨(dú)立預(yù)測(cè)冠心病及血管損傷嚴(yán)重程度的因子,因而逐漸引起臨床及科研工作者重視,通過(guò)降低身體內(nèi)CRP水平不僅可以抑制炎癥的進(jìn)展也可以起到預(yù)防動(dòng)脈粥樣硬化的作用。TNF-α(Tumor necrosis factor--α)即腫瘤壞死因子α,主要由巨噬細(xì)胞分泌,其他可以分泌TNF-α還有血管內(nèi)皮細(xì)胞、單核細(xì)胞等,除可殺傷并抑制腫瘤細(xì)胞外,還可促進(jìn)局部炎癥反應(yīng),并誘導(dǎo)相關(guān)細(xì)胞因子的產(chǎn)生,進(jìn)而在機(jī)體細(xì)胞的功能調(diào)節(jié)、炎癥反應(yīng)和免疫等方面發(fā)揮重要作用,對(duì)于心血管系統(tǒng),TNF-α可以誘發(fā)心肌細(xì)胞凋亡并降低心肌收縮力。TNF-α在AS形成的過(guò)程中發(fā)揮了重要作用,能增強(qiáng)動(dòng)脈粥樣硬化斑塊中巨噬細(xì)胞的吞噬作用并誘導(dǎo)釋放大量炎性因子,進(jìn)而可以損傷血管內(nèi)皮,激活內(nèi)源性凝血途徑,并增加血管通透性,導(dǎo)致局部血栓形成,參與AS的形成。心肌細(xì)胞在缺血、缺氧、病毒感染情況下可表達(dá)并分泌TNF-α。而過(guò)度表達(dá)的TNF-α反過(guò)來(lái)又可損傷心肌,加重心功能不全。相關(guān)研究發(fā)現(xiàn),降低大鼠體內(nèi)TNF-α水平可以改善大鼠心功能。因此本實(shí)驗(yàn)中選用TNF-α作為觀測(cè)心臟損傷的指標(biāo),具有重要的臨床及科研意義。芪參還五膠囊是河北省滄州中西醫(yī)結(jié)合醫(yī)院自主研發(fā)并生產(chǎn)的中成藥,該藥既吸取了傳統(tǒng)中醫(yī)對(duì)冠心病病機(jī)的研究,又兼顧現(xiàn)代中藥研究成果,在補(bǔ)陽(yáng)還五湯的基礎(chǔ)上加用全蟲(chóng)等組分�，F(xiàn)代研究表明黃芪能提高機(jī)體清除自由基及抗脂質(zhì)過(guò)氧化的能力,進(jìn)而增強(qiáng)機(jī)體抗氧化的能力,同時(shí)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預(yù)防及治療。水蛭、地龍可減輕心肌組織的炎癥反應(yīng),改善血液循環(huán),有利于心肌功能的恢復(fù),與黃芪合用可增強(qiáng)抗血小板預(yù)防血栓形成的功能,并可以改善局部及全身血液循環(huán)狀態(tài)。本實(shí)驗(yàn)中,通過(guò)飼喂高脂飲食及注射垂體后葉素模擬冠心病發(fā)生發(fā)展的自然病程制作大鼠冠心病模型,然后應(yīng)用芪參還五膠囊生藥灌胃,之后監(jiān)測(cè)炎性指標(biāo)并觀察心臟心肌及冠脈的病理變化,揭示中藥治療冠心病的原理,為中藥治療冠心病提供新的理論依據(jù)。實(shí)驗(yàn)方法:1雄性SD大鼠共56只隨機(jī)分成2組,分別為空白組13只、造模組43只,空白組給予普通大鼠維持飼料飼喂,造模組大鼠給予高脂飼料飼喂8周以造成血脂異常模型,8周后飼造模組大鼠給予垂體后葉素30U/kg腹腔注射連續(xù)3天,以造成冠心病大鼠模型,空白組給予同等體積蒸餾水腹腔注射,禁食水24小時(shí)后空白組及造模組分別隨機(jī)取抽取3只大鼠,摘取心臟,固定,進(jìn)行病理切片及鏡下觀察。2造模組分為實(shí)驗(yàn)組、低劑量組、中劑量組、高劑量組,其中低中高劑量組依據(jù)體重每日分別給予芪參還五膠囊生藥藥物溶液灌胃一次,劑量分別為0.125g/(kg·d)、0.25g/(kg·d)、0.5g/(kg·d),空白組及實(shí)驗(yàn)組則依據(jù)大鼠體重每日給予生理鹽水灌胃,共計(jì)28天。3灌胃結(jié)束后,禁食水24小時(shí),以10%水合氯醛3ml/kg腹腔注射麻醉,腹主動(dòng)脈取血,然后以3500r/min轉(zhuǎn)速離心血液15分鐘,取上層清液,冷凍保存,留備檢測(cè)炎性因子等相關(guān)指標(biāo),腹主動(dòng)脈注射甲醛溶液,待心肌組織變白,且大鼠四肢不自主抽搐,摘取心肌組織,以4%多聚甲醛固定,備做病理檢測(cè)。統(tǒng)計(jì)學(xué)方法:應(yīng)用SPSS21.0軟件進(jìn)行統(tǒng)計(jì)學(xué)分析。計(jì)量資料采用均數(shù)加減標(biāo)準(zhǔn)差(?)表示,兩樣本間用t檢驗(yàn),多個(gè)樣本均數(shù)則采用方差分析(LSD-t),檢驗(yàn)水準(zhǔn)α=0.05。結(jié)果:1成功復(fù)制出大鼠冠心病、心肌缺血模型;2芪參還五膠囊可降低冠心病大鼠血清中hs-CRP、TNF-α濃度,且差異具有統(tǒng)計(jì)學(xué)意義。3低、中、高劑量的芪參還五膠囊對(duì)于降低大鼠血清中hs-CRP和TNF-α的效果不完全同。4芪參還五膠囊可明顯改善冠脈血管內(nèi)皮形態(tài),減少缺血灶的產(chǎn)生,因而可證明對(duì)心肌缺血具有一定改善作用。結(jié)論:芪參還五膠囊可降低炎性因子的程度與生藥劑量相關(guān),并且通過(guò)降低炎性因子的方法,達(dá)到抗心肌缺血的目的,對(duì)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.

【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R285.5

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