本文選題：ATRA + 動(dòng)脈粥樣硬化　； 參考：《安徽醫(yī)科大學(xué)》2017年碩士論文

【摘要】：背景眾所周知,動(dòng)脈粥樣硬化是一種發(fā)生在動(dòng)脈內(nèi)壁的慢性炎癥性疾病,其發(fā)病機(jī)制尚未完全闡明。越來越多的證據(jù)表明,血管內(nèi)皮功能障礙與心血管事件密切相關(guān)。因此,正確認(rèn)識(shí)影響血管的收縮和舒張功能的因子失衡,對(duì)于了解并干預(yù)動(dòng)脈粥樣硬化的發(fā)病起重要作用。內(nèi)皮細(xì)胞可以分泌調(diào)節(jié)因子,包括一氧化氮(NO)和內(nèi)皮素(ET),從而調(diào)節(jié)血管松弛和收縮。全反式維甲酸(Retinoic Acid,ATRA)是維生素A的天然衍生物,可通過調(diào)節(jié)炎癥因子來改善動(dòng)脈粥樣硬化。然而,關(guān)于全反式維甲酸對(duì)動(dòng)脈內(nèi)皮功能的作用的研究較少見。本文,我們通過研究在動(dòng)脈粥樣硬化兔中,全反式維甲酸對(duì)血管內(nèi)皮產(chǎn)生的內(nèi)皮素-1(ET-1)和一氧化氮(NO)水平的影響來探討全反式維甲酸對(duì)動(dòng)脈粥樣硬化的作用機(jī)制。目的本研究選擇普通新西蘭白兔作為動(dòng)物模型,觀察全反式維甲酸對(duì)動(dòng)脈粥樣硬化兔血管內(nèi)皮的內(nèi)皮素-1和一氧化氮的影響,從而探討全反式維甲酸對(duì)動(dòng)脈粥樣硬化的作用機(jī)制。方法24只普通新西蘭白兔適應(yīng)性飼養(yǎng)一周后,隨機(jī)分為三組(n=8):A為正常對(duì)照組,B為高脂組,C為ATRA干預(yù)組。正常對(duì)照組予以普通飼料喂養(yǎng),高脂組給予高脂飼料喂養(yǎng),ATRA干預(yù)組為高脂飼料喂養(yǎng),高脂飲食4周后,開始加ATRA(10mg/(kg·d))灌胃干預(yù),并繼續(xù)予以高脂飲食喂養(yǎng)。12周后,采集血標(biāo)本和胸主動(dòng)脈標(biāo)本,觀察主動(dòng)脈斑塊形成情況,測(cè)定兔的血脂水平、動(dòng)脈內(nèi)膜通透性、血液e NOS活性、內(nèi)皮素(ET-1)、血漿一氧化氮(NO)含量;采用Western blot檢測(cè)主動(dòng)脈中ET-1,內(nèi)皮一氧化氮合酶(e NOS)和e NOS磷酸化的產(chǎn)物(p-e NOS)的水平。結(jié)果1.ATRA減輕動(dòng)脈粥樣硬化兔血管內(nèi)壁斑塊形成:油紅O染色肉眼可見,正常對(duì)照組,血管內(nèi)壁光滑,基本無斑塊形成。高脂組內(nèi)壁可見明顯大面積斑塊形成,凹凸不平。ATRA干預(yù)組主動(dòng)脈內(nèi)壁有斑塊形成,與高脂組相比明顯較少。HE染色后,光鏡下可見正常組動(dòng)脈壁內(nèi)膜光滑連續(xù),無內(nèi)膜增厚,平滑肌細(xì)胞排列整齊,彈性纖維稍紊亂。與正常組相比,高脂組動(dòng)脈壁內(nèi)膜顯著增厚,彈力板多處斷裂,可見粥樣斑塊大量形成,斑塊中可見炎性細(xì)胞、泡沫細(xì)胞。ATRA干預(yù)組在藥物干預(yù)后,其動(dòng)脈壁內(nèi)膜可見少量斑塊形成,與高脂組相比,脂肪細(xì)胞和炎性細(xì)胞明顯減少。2.ATRA降低動(dòng)脈粥樣硬化兔的血脂水平:由于脂質(zhì)水平與動(dòng)脈粥樣硬化的進(jìn)程關(guān)系密切,我們檢測(cè)了各組的膽固醇、甘油三酯、高密度脂蛋白、低密度脂蛋白。與正常組相比較,高脂組的膽固醇、甘油三酯、低密度脂蛋白明顯增高(P0.05),高密度脂蛋白降低(P0.05)。而ATRA干預(yù)組的膽固醇、甘油三酯、低密度脂蛋白均比高脂組減低,高密度脂蛋白較高(P0.05)。3.ATRA降低動(dòng)脈粥樣硬化兔的動(dòng)脈內(nèi)皮通透性:在熒光顯微鏡下,可以觀察到熒光染料在對(duì)照組中幾乎沒有穿透,但滲透高脂組動(dòng)脈壁的全層,ATRA干預(yù)組中熒光染料的穿透率顯著低于高脂組,但比對(duì)照組增加。4.ATRA影響動(dòng)脈粥樣硬化兔主動(dòng)脈中ET-1,e NOS和p-e NOS的表達(dá):Western blot結(jié)果顯示,與對(duì)照組相比較,高脂組兔動(dòng)脈組織中ET-1的表達(dá)明顯升高,而ATRA干預(yù)組的ET-1表達(dá)量介于對(duì)照組和高脂組之間。此外,關(guān)于e NOS磷酸化的產(chǎn)物Ser-1177(p-e NOS)的水平,p-e NOS在高脂組中的表達(dá)低于對(duì)照組,在用ATRA干預(yù)之后,其表達(dá)量明顯增加。而ATRA的干預(yù)對(duì)e NOS的表達(dá)并無統(tǒng)計(jì)學(xué)意義。5.ATRA對(duì)動(dòng)脈粥樣硬化兔血中e NOS活性和ET-1、NO水平的影響:結(jié)果表明,高脂組NO含量顯著低于對(duì)照組(P0.05),ATRA處理后eNOS活性和NO含量顯著升高(P0.05)。ET-1的檢測(cè)結(jié)果與NO的水平相反,ATRA組的ET-1表達(dá)明顯低于高脂組(P0.05)。結(jié)論NO和ET之間的平衡調(diào)節(jié)是預(yù)防和治療動(dòng)脈粥樣硬化的一個(gè)重要途徑。在本實(shí)驗(yàn)中顯示,ATRA可以減少血漿中ET-1的含量,通過增加e NOS磷酸化增加NO含量,并通過調(diào)節(jié)兩者之間的平衡,從而改善血管松弛,減輕動(dòng)脈粥樣硬化斑塊形成。它將為未來動(dòng)脈粥樣硬化的臨床治療提供新的方向。
[Abstract]:As we all know, atherosclerosis is a chronic inflammatory disease occurring on the inner wall of the artery. Its pathogenesis has not been fully elucidated. More and more evidence suggests that vascular endothelial dysfunction is closely related to cardiovascular events. Therefore, it is necessary to understand the imbalance of factors affecting vasodilation and diastolic function of blood vessels and to understand and do it. Preatheromatous disease plays an important role. Endothelial cells secrete regulatory factors, including nitric oxide (NO) and endothelin (ET), which regulate vascular relaxation and contraction. Retinoic Acid (ATRA) is a natural derivative of vitamin A, which can be used to improve atherosclerosis by regulating inflammatory factors. The effect of trans retinoic acid on the function of arterial endothelial cells is rare. In this article, we studied the effect of all trans retinoic acid on the levels of endothelin -1 (ET-1) and nitric oxide (NO) produced by vascular endothelium in atherosclerotic rabbits. The effect of all trans retinoic acid on endothelin -1 and nitric oxide in vascular endothelial cells of atherosclerotic rabbits was observed as an animal model, and the mechanism of all trans retinoic acid on atherosclerosis was investigated. Methods 24 New Zealand rabbits were randomly divided into three groups (n=8) after a week of adaptive feeding: A was normal. Group B was high fat group and C was ATRA intervention group. Normal control group was fed with ordinary diet, high fat group was fed with high fat diet, ATRA intervention group was fed with high fat diet, and after 4 weeks of high fat diet, ATRA (10mg/ (kg. D)) was added to stomach intervention, and the high fat diet was continued to be fed for.12 weeks, and blood specimens and thoracic aorta specimens were collected to observe the main body of the aorta. Atherosclerotic plaque formation, blood lipid level, intima permeability, e NOS activity, endothelin (ET-1), plasma nitric oxide (NO) levels, and the levels of ET-1, endothelial nitric oxide synthase (E NOS) and E NOS phosphorylation in the aorta of the aorta were measured by Western blot. Plaque formation in the inner wall: oil red O staining was visible to the naked eye, in the normal control group, the inner wall of the blood vessel was smooth, and the plaque formed basically. The inner wall of the high fat group showed obvious large area plaque formation. The inner wall of the aorta was formed in the unflat.ATRA intervention group. The smooth connection of the intima of the normal artery wall was visible in the normal group after the light microscope compared with the high fat group. Continued, without intimal thickening, smooth muscle cells arranged neatly, elastic fiber slightly disorder. Compared with the normal group, the intima of the arterial wall of the high fat group was thickened, the elastic plate was fractured in many places, the atherosclerotic plaque was seen in a large number, the plaque was visible in the plaque, and the.ATRA intervention group of the foam cells showed a small amount of plaque formation in the intima of the arterial wall. Compared with the high fat group, the fat cells and inflammatory cells significantly reduced.2.ATRA to reduce the level of blood lipid in atherosclerotic rabbits. Due to the close relationship between the lipid level and the process of atherosclerosis, we detected the cholesterol, triglycerides, high density lipoprotein and low density lipoprotein in each group. Oil three ester, low density lipoprotein (P0.05) and high density lipoprotein decreased (P0.05). The cholesterol, triglyceride and low density lipoprotein in the ATRA intervention group were lower than those in the high fat group, and the high density lipoprotein (P0.05).3.ATRA reduced the arterial endothelial permeability in atherosclerotic rabbits: fluorescence staining could be observed under the fluorescence microscope. There was little penetration in the control group, but the penetration rate of the fluorescent dye in the ATRA intervention group was significantly lower than that in the high fat group, but the increase of.4.ATRA in the aorta of the atherosclerotic rabbits influenced the expression of ET-1, e NOS and P-E NOS in the atherosclerotic rabbits. The result of Western blot showed that the rabbit artery in the high fat group was compared with the control group. The expression of ET-1 in the tissue was significantly increased, while the expression of ET-1 in the ATRA intervention group was between the control group and the high fat group. In addition, the expression of P-E NOS in the high fat group was lower than the control group on the level of the product Ser-1177 (P-E NOS) of the product of E NOS phosphorylation. The effect of statistical significance.5.ATRA on the activity of E NOS and the level of ET-1 and NO in the blood of atherosclerotic rabbits showed that the content of NO in the high fat group was significantly lower than that of the control group (P0.05), and the eNOS activity and the NO content of the NO increased significantly (P0.05) after ATRA treatment (P0.05), and the expression of.ET-1 was significantly lower than that of the high fat group. Balance regulation with ET is an important way to prevent and treat atherosclerosis. In this experiment, ATRA can reduce the content of ET-1 in plasma, increase NO content by increasing e NOS phosphorylation, and regulate the balance between the two, thus improving vascular relaxation and reducing the formation of atherosclerotic plaques. To provide new directions for clinical treatment of atherosclerosis.

【學(xué)位授予單位】：安徽醫(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)】：R543.5

【相似文獻(xiàn)】

相關(guān)期刊論文 前10條

1 王俊和,陶榮亞,時(shí)昊,紀(jì)淑儀,付承彬,王信琪;全反式維甲酸治療急性早幼粒細(xì)胞白血病18例[J];醫(yī)師進(jìn)修雜志;1991年10期

2 張吉仙;程定珍;張縉鸞;溫丙昭;哈力代;付美蘭;;全反式維甲酸治療急性早幼粒細(xì)胞白血病14例臨床分析[J];新疆醫(yī)學(xué)院學(xué)報(bào);1993年01期

3 陳鈺，吳方，李軍民，張芬琴，沈志祥;小劑量全反式維甲酸治療早幼粒細(xì)胞白血病療效分析[J];中華血液學(xué)雜志;1995年02期

4 李艷榮，，陳全英，唐密;全反式維甲酸治療骨髓增生異常綜合征4例[J];中國冶金工業(yè)醫(yī)學(xué)雜志;1995年04期

5 王衛(wèi)東,張?jiān)闯?全反式維甲酸的副作用及防治措施[J];新醫(yī)學(xué);1996年11期

6 孟凡義,樓方定,于力,李新梅,張伯龍;小劑量全反式維甲酸治療急性早幼粒細(xì)胞白血病5例報(bào)告[J];白血病;1996年01期

7 胡飛虎,張俊;全反式維甲酸治療痤瘡62例療效觀察[J];中國皮膚性病學(xué)雜志;1997年03期

8 張曉玲,方復(fù)海,王九如,陳天榮,蔡益鵬;國產(chǎn)全反式維甲酸治療急性早幼粒細(xì)胞性白血病40例療效分析[J];蘇州醫(yī)學(xué)院學(xué)報(bào);1997年05期

9 劉陶文;全反式維甲酸治療急性早幼粒細(xì)胞白血病的不良反應(yīng)[J];藥學(xué)進(jìn)展;1998年04期

10 李志,李艷紅,包阿巾;全反式維甲酸治療急性早幼粒細(xì)胞白血病17例臨床分析[J];黑龍江醫(yī)藥科學(xué);2000年05期

相關(guān)會(huì)議論文 前10條

1 張玉珍;;全反式維甲酸治療急性早幼粒細(xì)胞白血病的護(hù)理[A];全國腫瘤護(hù)理學(xué)術(shù)交流暨專題講座會(huì)議論文匯編[C];2008年

2 唐善浩;裴仁治;;全反式維甲酸治療急性早幼粒細(xì)胞白血病耐藥機(jī)制的研究進(jìn)展[A];2012年浙江省血液病學(xué)年會(huì)論文集[C];2012年

3 薛蓉;朱依純;;全反式維甲酸抑制血管平滑肌增殖的作用機(jī)制[A];中國生理學(xué)會(huì)論文匯編2006年第二期[C];2006年

4 劉慶喜;王楠;廖興華;任光達(dá);秦濤;俞如發(fā);程彩蓮;劉廣存;張同存;;全反式維甲酸誘導(dǎo)人神經(jīng)膠質(zhì)瘤細(xì)胞的分化[A];“細(xì)胞活動(dòng) 生命活力”——中國細(xì)胞生物學(xué)學(xué)會(huì)全體會(huì)員代表大會(huì)暨第十二次學(xué)術(shù)大會(huì)論文摘要集[C];2011年

5 趙慶英;;全反式維甲酸治療急性早幼粒細(xì)胞性白血病的副反應(yīng)觀察及護(hù)理[A];全國內(nèi)科護(hù)理學(xué)術(shù)交流暨專題講座會(huì)議論文匯編[C];2004年

6 張英;劉飛;郭華北;齊慧伶;陳惠黎;;全反式維甲酸抑制肝癌細(xì)胞的轉(zhuǎn)移表型[A];第八屆全國肝癌學(xué)術(shù)會(huì)議論文匯編[C];2001年

7 呂章春;朱佩禎;朗香花;陳銀巧;;三氧化二砷聯(lián)合全反式維甲酸治療急性早幼粒細(xì)胞白血病13例療效觀察[A];第三屆浙江中西部科技論壇論文集（第七卷 醫(yī)學(xué)、抗癌分卷）[C];2006年

8 王小扁;韓建雄;胡澤平;周青;朱華慶;汪淵;;全反式維甲酸通過下調(diào)小窩蛋白1表達(dá)和上調(diào)內(nèi)皮型一氧化氮合酶活性改善動(dòng)脈粥樣硬化兔內(nèi)皮功能[A];第11屆全國脂質(zhì)與脂蛋白學(xué)術(shù)會(huì)議論文匯編[C];2012年

9 張延順;豐雷;王勇;;全反式維甲酸治療急性早幼粒細(xì)胞白血病致嚴(yán)重副反應(yīng)1例并文獻(xiàn)復(fù)習(xí)[A];2005年華東六省一市血液病學(xué)學(xué)術(shù)會(huì)議暨浙江省血液病學(xué)學(xué)術(shù)年會(huì)論文匯編[C];2005年

10 劉少軍;李曼;丁峰;顧勇;林善錟;;一步提取法測(cè)定全反式維甲酸[A];“中華醫(yī)學(xué)會(huì)腎臟病學(xué)分會(huì)2004年年會(huì)”暨“第二屆全國中青年腎臟病學(xué)術(shù)會(huì)議”論文匯編[C];2004年

相關(guān)重要報(bào)紙文章 前10條

1 通訊員 李靜 記者 胡德榮;全反式維甲酸可抑制肺移植排斥反應(yīng)[N];健康報(bào);2012年

2 ;全反式維甲酸促進(jìn)造血干／祖細(xì)胞植入的實(shí)驗(yàn)研究[N];中國醫(yī)藥報(bào);2003年

3 仇逸;急性早幼粒細(xì)胞白血病治愈有望[N];中國醫(yī)藥報(bào);2004年

4 特約記者 汪敏;上海瑞金醫(yī)院治療白血病再探新路[N];家庭醫(yī)生報(bào);2003年

5 張建松 張學(xué)全;我國科學(xué)家揭示白血病治療的基因調(diào)控網(wǎng)絡(luò)[N];中國醫(yī)藥報(bào);2000年

6 胡德榮;上海瑞金醫(yī)院白血病治療創(chuàng)奇跡[N];中國醫(yī)藥報(bào);2003年

7 記者 仇逸;急性早幼粒細(xì)胞白血病中西醫(yī)結(jié)合有望治愈[N];新華每日電訊;2004年

8 牛嚴(yán);讓癌細(xì)胞“改邪歸正”[N];大眾科技報(bào);2001年

9 王卉;小劑量砒霜 由毒變藥治血癌[N];大眾科技報(bào);2000年

10 周 晉 孟 然;砷制劑治療白血病臨床要點(diǎn)[N];中國中醫(yī)藥報(bào);2004年

相關(guān)博士學(xué)位論文 前7條

1 仲晨;全反式維甲酸在肝缺血再灌注損傷中的作用機(jī)制研究[D];南京醫(yī)科大學(xué);2016年

2 于磊;轉(zhuǎn)錄因子CEBPB在全反式維甲酸誘導(dǎo)急性早幼粒細(xì)胞白血病中靶基因的確認(rèn)（合成生物學(xué)在醫(yī)學(xué)中的應(yīng)用）[D];中南大學(xué);2013年

3 綦斌;全反式維甲酸誘導(dǎo)大鼠C6腦膠質(zhì)瘤凋亡的實(shí)驗(yàn)研究[D];吉林大學(xué);2006年

4 李慶;外周Th17/Treg失衡在動(dòng)脈粥樣硬化中的作用及全反式維甲酸對(duì)其的影響和機(jī)制[D];安徽醫(yī)科大學(xué);2010年

5 鐘久昌;自發(fā)性高血壓大鼠體內(nèi)RAS相關(guān)基因的表達(dá)及全反式維甲酸對(duì)其影響的研究[D];汕頭大學(xué);2005年

6 劉向榮;AML1a在小鼠造血細(xì)胞增殖分化異常及惡性轉(zhuǎn)化中的作用及全反式維甲酸處理NB4細(xì)胞的微小RNA表達(dá)譜分析[D];中國協(xié)和醫(yī)科大學(xué);2008年

7 于利;全反式維甲酸誘導(dǎo)同種心臟移植耐受[D];華中科技大學(xué);2010年

相關(guān)碩士學(xué)位論文 前10條

1 廖偉超;依維莫司協(xié)同全反式維甲酸對(duì)耐藥急性早幼粒細(xì)胞白血病的作用及機(jī)制研究[D];浙江大學(xué);2015年

2 彭時(shí)平;全反式維甲酸處理下HL-60細(xì)胞增殖、分化及滾動(dòng)黏附的研究[D];華南理工大學(xué);2014年

3 申欣;維甲酸誘導(dǎo)基因JWA與DNA拓?fù)洚悩?gòu)酶Ⅱα的相互調(diào)控及全反式維甲酸對(duì)DNA拓?fù)洚悩?gòu)酶Ⅱα的下調(diào)作用研究[D];南京醫(yī)科大學(xué);2013年

4 高珊;全反式維甲酸通過Sp1/Sp3位點(diǎn)調(diào)節(jié)CD2AP基因的表達(dá)[D];南京醫(yī)科大學(xué);2013年

5 柳飛;全反式維甲酸與三氧化二砷聯(lián)合化療治療急性早幼粒細(xì)胞白血病的療效分析[D];鄭州大學(xué);2016年

6 崔會(huì)娟;全反式維甲酸聯(lián)合LY294002對(duì)食管癌EC1細(xì)胞增殖、遷移及PI3K、MMP-2表達(dá)的影響[D];鄭州大學(xué);2016年

7 蔣鵬;全反式維甲酸一般藥理學(xué)、急性毒性和長期毒性研究[D];浙江大學(xué);2016年

8 陳春琳;全反式維甲酸調(diào)節(jié)糖尿病大鼠腎臟ACE/ACE2表達(dá)抑制腎臟纖維化的研究[D];福建醫(yī)科大學(xué);2016年

9 陶琳琳;全反式維甲酸對(duì)動(dòng)脈粥樣硬化兔內(nèi)皮功能調(diào)節(jié)的探究[D];安徽醫(yī)科大學(xué);2017年

10 劉文賓;全反式維甲酸治療難治性特發(fā)性血小板減少性紫癜的療效觀察及其機(jī)理研究[D];蘇州大學(xué);2009年

本文編號(hào)：1842191