本文選題：急性心肌梗死　切入點(diǎn)：無(wú)復(fù)流　出處：《遼寧醫(yī)學(xué)院》2013年碩士論文　論文類型：學(xué)位論文

【摘要】：目的 研究替羅非班對(duì)大鼠急性心肌梗死再灌注后無(wú)復(fù)流的影響，并探討其改善無(wú)復(fù)流的可能機(jī)制。 方法 雄性SD大鼠56只,隨機(jī)分為四組：假手術(shù)組（Sham組，8只）、急性心肌梗死再灌注組（AMI/R組，16只）、替羅非班組（Tiro組，16只）和替羅非班聯(lián)合一氧化氮合酶抑制劑N-硝基-左旋精氨酸組（Tiro+L-NNA組，16只）。通過(guò)結(jié)扎冠脈左前降支60分鐘，再灌注120分鐘，建立大鼠急性心肌梗死再灌注無(wú)復(fù)流模型，假手術(shù)組只穿線不結(jié)扎。再灌注120分鐘時(shí)進(jìn)行血流動(dòng)力學(xué)測(cè)定；心肌染色評(píng)估大鼠無(wú)復(fù)流范圍、缺血范圍及梗死范圍；分光光度計(jì)測(cè)定缺血區(qū)心肌組織一氧化氮合酶（NOS）活性；western blot檢測(cè)缺血區(qū)心肌內(nèi)皮型一氧化氮合酶(eNOS)、絲氨酸1177磷酸化eNOS（p-eNOS ser1177）及血管內(nèi)皮鈣粘蛋白（VE-cadherin）的表達(dá)，電鏡下觀察心肌微血管內(nèi)皮損傷情況。 結(jié)果 ①與Sham組比較，AMI/R組的LVESP、±dp/dtmax均降低，HR、LVEDP則升高，缺血區(qū)心肌eNOS活性降低，iNOS活性增高， p-eNOS ser1177含量增加,VE-cadherin含量減少(P均0.01)，微血管內(nèi)皮損傷程度加重，同時(shí)無(wú)復(fù)流范圍及梗死范圍與既往文獻(xiàn)相符；②與AMI/R組比較，Tiro組的LVESP、±dp/dtmax均升高，HR、LVEDP則降低，缺血區(qū)心肌eNOS活性明顯增高，iNOS活性明顯降低，p-eNOS ser1177,VE-cadherin含量顯著增加，微血管內(nèi)皮損傷程度減輕，無(wú)復(fù)流范圍及梗死范圍明顯縮�。≒均＜0.01）；③與Tiro組比較，Tiro+L-NNA組的LVESP、±dp/dtmax均降低，，HR、LVEDP則升高，缺血區(qū)心肌eNOS活性顯著降低（P均0.01），而iNOS活性兩組間無(wú)統(tǒng)計(jì)學(xué)差異（P0.05），p-eNOS ser1177，VE-cadherin含量顯著降低（P均0.01），微血管內(nèi)皮損傷加重，無(wú)復(fù)流范圍及梗死范圍增大（P0.01）。 結(jié)論 ①替羅非班可顯著減小大鼠急性心肌梗死再灌注后的無(wú)復(fù)流范圍及梗死范圍，改善心功能；②替羅非班可通過(guò)誘導(dǎo)大鼠AMI再灌注后eNOS磷酸化而提高eNOS活性，釋放更多內(nèi)皮源性NO，保護(hù)微血管內(nèi)皮功能；增加VE-cadherin含量，減輕微血管內(nèi)皮損傷，這可能是其減輕無(wú)復(fù)流的主要機(jī)制；③一氧化氮合酶抑制劑L-NNA可部分阻斷上述保護(hù)效應(yīng)，提示替羅非班防治無(wú)復(fù)流的作用與eNOS有關(guān)。
[Abstract]:Purpose. To study the effect of tirofiban on no reflow after reperfusion in rats with acute myocardial infarction, and to explore the possible mechanism of its improvement. Method. 56 male SD rats, They were randomly divided into four groups: sham-operated group (n = 8), acute myocardial infarction reperfusion group (n = 16) and tirofiban group (n = 16) and Tiro L-NNA group (n = 16). The left anterior descending coronary artery was ligated for 60 minutes. After 120 minutes of reperfusion, the model of no reflow was established in rats with acute myocardial infarction and reperfusion. In the sham operation group, there was no ligation through the thread. The hemodynamics was measured at 120 minutes after reperfusion, and the range of no reflow was evaluated by myocardial staining. The activity of nitric oxide synthase (NOS) in ischemic myocardium was measured by spectrophotometer and the expression of endothelial nitric oxide synthase (Enos), serine 1177 phosphorylated eNOS(p-eNOS serine (serine 1177) and vascular endothelial cadherin (VE-cadherin) were detected by western blot. The injury of myocardial microvascular endothelium was observed under electron microscope. Results. 1Compared with Sham group, LVESPand 鹵dp/dtmax of AMI / R group were decreased, the activity of eNOS in ischemic myocardium was decreased, the activity of iNOS was increased, the content of p-eNOS ser1177 was increased and the content of VE-cadherin was decreased (P < 0.01), and the degree of microvascular endothelial injury was aggravated. At the same time, the extent of no reflow and infarct size were consistent with previous literatures. Compared with AMI/R group, the LVESPand 鹵dp/dtmax of Tiro group were increased, and the activity of eNOS in ischemic myocardium was significantly increased. The activity of eNOS in ischemic myocardium was significantly increased and the level of VE-cadherin was significantly increased, and the degree of microvascular endothelial injury was alleviated. Compared with Tiro group, LVESPand 鹵dp/dtmax of Tiro L-NNA group decreased significantly (P < 0.01), and the LVEDP of Tiro L-NNA group decreased significantly (P < 0.01). Myocardial eNOS activity in ischemic area decreased significantly (P < 0.01), while there was no significant difference in the activity of iNOS between the two groups. The contents of p-eNOS ser1177 and VE-cadherin in ischemic myocardium decreased significantly (P < 0.01), and the injury of microvascular endothelium was aggravated, the area without reflow and the infarct area were increased (P 0.01). Conclusion. 1tirofiban could significantly reduce the non-reflow area and infarct size after reperfusion of acute myocardial infarction in rats. Tirofiban could improve the activity of eNOS by inducing eNOS phosphorylation after AMI reperfusion in rats. Release more endothelium-derived no, protect microvascular endothelial function, increase VE-cadherin content and reduce microvascular endothelial injury, which may be its main mechanism of relieving non-reflux. L-NNA, a nitric oxide synthase inhibitor, can partially block the above protective effects. The results suggest that the effect of tirofiban on prevention and treatment of no reflow is related to eNOS.
【學(xué)位授予單位】：遼寧醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2013
【分類號(hào)】：R542.22

【參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 黃雨勝;張英杰;;阿托伐他汀對(duì)大鼠心肌缺血再灌注后無(wú)復(fù)流的影響[J];廣東醫(yī)學(xué);2012年07期

2 譚鳳梅;韋星;顏姝;馮大明;;內(nèi)皮細(xì)胞損傷與心肌無(wú)復(fù)流現(xiàn)象[J];中國(guó)動(dòng)脈硬化雜志;2013年01期

3 許立慶;李東寶;劉志;;預(yù)防急性心梗支架后慢血流臨床研究[J];山東醫(yī)藥;2009年28期

4 岳志杰;余志斌;;一氧化氮對(duì)心肌的抑制性保護(hù)作用[J];生理學(xué)報(bào);2011年03期

5 張金剛;史曉俊;王本芳;;冠狀動(dòng)脈無(wú)復(fù)流的研究進(jìn)展[J];中國(guó)全科醫(yī)學(xué);2012年36期

6 李新強(qiáng);陳海生;鐘煥清;董家壽;易軍;;四氫生物蝶呤與左旋精氨酸對(duì)幼兔心肌保護(hù)效果的對(duì)比研究[J];心臟雜志;2011年01期

7 趙克森,黃巧冰;血管通透性增高的基本機(jī)制[J];中國(guó)病理生理雜志;2003年04期

8 楊秀秀;陳韻岱;田峰;駱景光;呂媛;呂樹錚;;葛根素對(duì)兔急性心肌梗死再灌注后無(wú)復(fù)流的影響[J];中國(guó)循環(huán)雜志;2010年01期

9 趙京林,楊躍進(jìn),吳永建,荊志成,尤士杰,楊偉憲,孟亮,田毅,陳紀(jì)林,高潤(rùn)林,陳在嘉;抗血小板藥物對(duì)豬急性心肌梗死再灌注后無(wú)再流的影響[J];中華醫(yī)學(xué)雜志;2005年31期

10 陳藝;顏紅兵;;心肌缺血再灌注后無(wú)復(fù)流發(fā)生的分子機(jī)制[J];中國(guó)介入心臟病學(xué)雜志;2011年03期

本文編號(hào)：1612578