替罗非班对大鼠急性心肌梗死再灌注后无复流的影响

发布时间：2018-03-14 19:28

本文选题：急性心肌梗死　切入点：无复流　出处：《辽宁医学院》2013年硕士论文　论文类型：学位论文

【摘要】：目的研究替罗非班对大鼠急性心肌梗死再灌注后无复流的影响，并探讨其改善无复流的可能机制。方法雄性SD大鼠56只,随机分为四组：假手术组（Sham组，8只）、急性心肌梗死再灌注组（AMI/R组，16只）、替罗非班组（Tiro组，16只）和替罗非班联合一氧化氮合酶抑制剂N-硝基-左旋精氨酸组（Tiro+L-NNA组，16只）。通过结扎冠脉左前降支60分钟，再灌注120分钟，建立大鼠急性心肌梗死再灌注无复流模型，假手术组只穿线不结扎。再灌注120分钟时进行血流动力学测定；心肌染色评估大鼠无复流范围、缺血范围及梗死范围；分光光度计测定缺血区心肌组织一氧化氮合酶（NOS）活性；western blot检测缺血区心肌内皮型一氧化氮合酶(eNOS)、丝氨酸1177磷酸化eNOS（p-eNOS ser1177）及血管内皮钙粘蛋白（VE-cadherin）的表达，电镜下观察心肌微血管内皮损伤情况。结果 ①与Sham组比较，AMI/R组的LVESP、±dp/dtmax均降低，HR、LVEDP则升高，缺血区心肌eNOS活性降低，iNOS活性增高， p-eNOS ser1177含量增加,VE-cadherin含量减少(P均0.01)，微血管内皮损伤程度加重，同时无复流范围及梗死范围与既往文献相符；②与AMI/R组比较，Tiro组的LVESP、±dp/dtmax均升高，HR、LVEDP则降低，缺血区心肌eNOS活性明显增高，iNOS活性明显降低，p-eNOS ser1177,VE-cadherin含量显著增加，微血管内皮损伤程度减轻，无复流范围及梗死范围明显缩小（P均＜0.01）；③与Tiro组比较，Tiro+L-NNA组的LVESP、±dp/dtmax均降低，，HR、LVEDP则升高，缺血区心肌eNOS活性显著降低（P均0.01），而iNOS活性两组间无统计学差异（P0.05），p-eNOS ser1177，VE-cadherin含量显著降低（P均0.01），微血管内皮损伤加重，无复流范围及梗死范围增大（P0.01）。结论 ①替罗非班可显著减小大鼠急性心肌梗死再灌注后的无复流范围及梗死范围，改善心功能；②替罗非班可通过诱导大鼠AMI再灌注后eNOS磷酸化而提高eNOS活性，释放更多内皮源性NO，保护微血管内皮功能；增加VE-cadherin含量，减轻微血管内皮损伤，这可能是其减轻无复流的主要机制；③一氧化氮合酶抑制剂L-NNA可部分阻断上述保护效应，提示替罗非班防治无复流的作用与eNOS有关。
[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 卤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 卤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 卤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.
【学位授予单位】：辽宁医学院
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R542.22

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