發(fā)布時(shí)間：2018-01-02 15:40

  本文關(guān)鍵詞：乙醇與急性心肌梗死后大鼠冠脈側(cè)枝循環(huán)的關(guān)系及干預(yù)研究　出處：《山東大學(xué)》2014年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 乙醇 心肌梗死 微血管密度 瑞舒伐他汀 VEGF 內(nèi)皮抑素

【摘要】：背景及目的 心血管疾病是當(dāng)前世界重要的死亡原因之一,家族史、年齡、高血壓、高膽固醇血癥、糖尿病、肥胖、飲酒等都是冠心病的危險(xiǎn)因素。飲酒作為冠心病可以改變的危險(xiǎn)因素之一,眾多來(lái)自于大型隊(duì)列研究及薈萃分析的流行病學(xué)研究表明,適量飲酒可以降低冠心病的風(fēng)險(xiǎn),與其發(fā)病率、死亡率的關(guān)系呈“U”或“J”字形曲線,而大量飲酒會(huì)導(dǎo)致冠狀動(dòng)脈的鈣化程度明顯升高,使冠心病的發(fā)病率、死亡率明顯增加。另外來(lái)自許多體外的實(shí)驗(yàn)研究顯示少量飲酒可以明顯提高內(nèi)皮血管內(nèi)皮生長(zhǎng)因子(VEGF)的表達(dá),從而促進(jìn)血管的新生,臨床研究也發(fā)現(xiàn)長(zhǎng)期少量飲酒的冠心病的患者具有豐富的冠脈側(cè)枝循環(huán)。然而長(zhǎng)期給予不同乙醇量對(duì)急性心肌梗死后缺血心肌內(nèi)血管新生的影響及其作用機(jī)制如何?目前尚缺乏這方面的研究。 羥甲基戊二酰輔酶A還原酶抑制劑(他汀)目前已是冠心病一級(jí)及二級(jí)預(yù)防的基石,臨床證據(jù)已經(jīng)充分表明,長(zhǎng)期給予他汀類藥物治療能夠顯著降低心血管事件發(fā)生的風(fēng)險(xiǎn),長(zhǎng)期應(yīng)用他汀的患者將明顯獲益,目前認(rèn)為其機(jī)制主要通過降脂、抗炎、抗氧化、保護(hù)血管內(nèi)皮細(xì)胞等作用發(fā)揮心血管保護(hù)功能。最新的研究還發(fā)現(xiàn),他汀類藥物可以抑制心室重構(gòu),并能夠促進(jìn)缺血心肌內(nèi)血管新生等心臟保護(hù)作用。因此我們提出假設(shè),若長(zhǎng)期大量飲酒對(duì)心肌梗死后缺血心肌內(nèi)冠脈側(cè)枝循環(huán)有抑制作用,那么長(zhǎng)期預(yù)防性應(yīng)用他汀類藥物是否能夠逆轉(zhuǎn)大量飲酒對(duì)血管新生的這種抑制作用?目前缺乏這方面的報(bào)道。 因此本實(shí)驗(yàn)首先利用急性心肌梗死動(dòng)物模型觀察長(zhǎng)期不同量乙醇攝入對(duì)缺血心肌內(nèi)血管新生及其血管生長(zhǎng)調(diào)節(jié)因子(包括VEGF和內(nèi)皮抑素)表達(dá)水平的影響,然而根據(jù)實(shí)驗(yàn)結(jié)果來(lái)驗(yàn)證提出的假設(shè)是否成立,若假設(shè)成立,則應(yīng)用他汀類藥物看是否可以逆轉(zhuǎn)大量飲酒對(duì)心肌血管新生的抑制作用,旨在為新的冠心病干預(yù)方式提供更多的理論支持。 第一部分乙醇對(duì)急性心肌梗死后大鼠冠脈側(cè)枝循環(huán)的影響 方法 選取225-275g雄性SD大鼠,適應(yīng)性喂養(yǎng)一周后；隨機(jī)分成4組：假手術(shù)組(不做任何干預(yù)處理),空白對(duì)照組(蒸餾水,5g·kg·d-1),乙醇干預(yù)組：小劑量(50%食用乙醇,0.5g·kg-1·d-1),大劑量(50%食用乙醇,5g·kg-1·d-1)。連續(xù)喂養(yǎng)4周后制作成心肌梗死模型,假手術(shù)組在相應(yīng)部位空穿一次；于術(shù)后第3天處死所有組別內(nèi)的大鼠,留取梗死邊緣區(qū)心肌組織,采用免疫組織化學(xué)SP法檢測(cè)梗死邊緣區(qū)心肌內(nèi)CD34微血管密度(MVD),應(yīng)用ELISA法測(cè)定梗死邊緣區(qū)心肌組織勻漿液中血管內(nèi)皮生長(zhǎng)因子(VEGF)及內(nèi)皮抑素的表達(dá)水平。通過方差分析研究各組間梗死邊緣區(qū)MVD及VEGF.內(nèi)皮抑素表達(dá)水平有無(wú)差異。 結(jié)果顯示 空白對(duì)照組與假手術(shù)組相比,MVD明顯增加[(88.7±3.4)N/mm2比(70.6±6.3)N/mm2,P0.05)]；VEGF.內(nèi)皮抑素水平也明顯升高[(318.7±18.6)pg/ml比(217.4±26.5)pg/ml；(306.9±53.9)ng/ml比(194.1±11.3)ng/ml,P0.05)]；與空白對(duì)照組相比,小劑量乙醇組MVD明顯增加[(128.6±12.9)N/mm2比(88.7±3.4)N/mm2,P0.05)],VEGF表達(dá)明顯升高[(438.2±46.2)pg/ml比(318.7±18.6)pg/ml,P0.05)],而內(nèi)皮抑素濃度明顯降低[(230.7±48.1)ng/ml比(306.9±53.9)ng/ml,P0.05)],而大劑量乙醇組與空白對(duì)照組相比,MVD明顯減少[(55.4±8.6)N/mm2比(88.7±3.4)N/mm2,P0.05)],VEGF水平雖無(wú)明顯差異,但內(nèi)皮抑素表達(dá)水平明顯升高[(437.5±66.7)ng/ml比(306.9±53.9)ng/ml,P0.05)]。 第二部分瑞舒伐他汀改善大量乙醇對(duì)急性心肌梗死后大鼠血管新生的影響 方法 選取225-275g雄性SD大鼠,設(shè)立瑞舒伐他汀預(yù)處理組：瑞舒伐他汀[(20mg·kg-1·d-1)+大劑量乙醇組(50%食用乙醇,5g·kg-1·d-1)],與第一部分的空白對(duì)照組(蒸餾水5g·kg-1·d-1)及大劑量乙醇組(50%乙醇,5g·kg-1·d-1)相比較,所有組別內(nèi)大鼠連續(xù)喂養(yǎng)4周后,制作心肌梗死動(dòng)物模型,術(shù)后第3天處死所有組別大鼠,留取梗死邊緣區(qū)存活心肌組織,采用免疫組織化學(xué)SP法檢測(cè)梗死邊緣區(qū)心肌內(nèi)CD34微血管密度(MVD),應(yīng)用ELISA法測(cè)定各組梗死邊緣區(qū)心肌組織勻漿液中血管內(nèi)皮生長(zhǎng)因子(VEGF)及內(nèi)皮抑素水平。 結(jié)果顯示 大劑量乙醇組與空白對(duì)照組相比的結(jié)果同第一部分,與大劑量乙醇組相比,瑞舒伐他汀預(yù)處理組MVD明顯增加[(73.1±3.2)N/mm2比(55.4±8.6)N/mm2,P0.05)]; VEGF表達(dá)略有升高,內(nèi)皮抑素有降低趨勢(shì),但與大量乙醇組相比均無(wú)明顯統(tǒng)計(jì)學(xué)差異。 結(jié)論 1.長(zhǎng)期飲酒可以影響急性心肌梗死后缺血心肌內(nèi)VEGF、內(nèi)皮抑素的表達(dá) 2.少量飲酒通過促進(jìn)VEGF,并抑制內(nèi)皮抑素的表達(dá)促進(jìn)冠脈側(cè)枝循環(huán)血管的新生； 3.長(zhǎng)期大量飲酒可抑制急性心肌梗死后缺血心肌的血管新生,作用機(jī)制可能與增加內(nèi)皮抑素的表達(dá)有關(guān)； 4.預(yù)防性給予瑞舒伐他汀能夠改善長(zhǎng)期大量飲酒后對(duì)心肌血管新生的抑制作用,但與VEGF和內(nèi)皮抑素表達(dá)無(wú)關(guān)；
[Abstract]:Background and purpose
Cardiovascular disease is a major cause of death in the world, family history, age, hypertension, hypercholesterolemia, diabetes, obesity, alcohol consumption is a risk factor for coronary heart disease. One of the risk factors of coronary heart disease as drinking can change, many from large cohort studies and meta-analysis of epidemiological studies showed that moderate drinking can reduce coronary heart disease the risk of mortality and morbidity, the relationship of a "U" or "J" shaped curve, a large number of drinking will lead to the calcification of coronary artery was increased, the incidence of coronary heart disease, mortality increased significantly. Experimental studies also showed in vitro from many small amounts of alcohol can significantly improve endothelial vascular endothelial growth factor (VEGF) expression, so as to promote angiogenesis, clinical studies also showed that the long-term drinking of the coronary heart disease patients with coronary collateral rich However, the effect of long-term ethanol dosage on angiogenesis in ischemic myocardium after acute myocardial infarction is still unclear.
HMG CoA reductase inhibitor A two (Ta Ting) is now a grade and two grade prevention of coronary heart disease and clinical evidence has indicated that chronic administration of Ta Ting drug treatment can significantly reduce the risk of cardiovascular events, long-term application of Ta Ting's patients will benefit significantly, it is suggested that the main mechanism by lipid-lowering, anti-inflammatory antioxidation and protection of vascular endothelial cells, play the role of the function of cardiovascular protection. Recent studies also found that Ta Ting drugs can inhibit ventricular remodeling, and can promote the myocardial protective effect of angiogenesis in the heart. So we propose the hypothesis that if a large number of long-term drinking of myocardial infarction after myocardial ischemia in coronary collateral circulation inhibition so, whether the application of long-term prevention of Ta Ting's drugs to reverse a large number of drinking this inhibitory effect on the angiogenesis of the lack of this? Report.
Therefore this experiment using an animal model of acute myocardial infarction on different long-term ethanol intake regulation factor on angiogenesis in ischemic myocardium and vascular growth (including VEGF and endostatin) expression levels, however, according to the experimental results to verify the proposed hypotheses, if the hypothesis is to see whether the use of statins can be reversed drinking a lot of inhibitory effects on myocardial angiogenesis, in order to provide more theoretical support for the new way of coronary intervention.
The effect of part one ethanol on coronary collateral circulation in rats after acute myocardial infarction
Method
Male 225-275g SD rats, feeding a week; randomly divided into 4 groups: sham operation group (without any treatment), control group (distilled water, 5g - kg - D-1), ethanol intervention group: low dose (50% ethanol, 0.5g - kg-1 - D-1), high dose (50% ethanol, 5g - kg-1 - D-1). After 4 weeks of continuous feeding into the model of myocardial infarction in a sham operation group in the corresponding position; on the third day after surgery were all in rats, the myocardial tissue edge area of infarction, using immunohistochemical SP method to detect myocardial infarction edge CD34 in the area of microvessel density (MVD), vascular endothelial growth factor in myocardial infarction tissue homogenate in marginal zone by ELISA (VEGF) and the expression of endostatin. Through the analysis of variance the difference between the expression of MVD and VEGF. in infarcted zone between each level of endostatin.
Results show
絀虹櫧瀵圭収緇勪笌鍋囨墜鏈粍鐩告瘮,MVD鏄庢樉澧炲姞[(88.7鹵3.4)N/mm2姣，

本文編號(hào)：1369875