环氧化酶在炎症因子引起大鼠冠状动脉无复流中的作用机制研究

Effect of cyclooxygenase on no-reflow phenom enon in acute myocardial infarction of rats

目的探讨环氧化酶(COX)在炎症因子引起的大鼠冠状动脉无复流现象中的作用及机制。方法采用结扎-放松冠状动脉左前降支法建立大鼠无复流模型,硫磺素S法测定离体大鼠左心室心肌无复流面积,根据左心室无复流面积将实验大鼠分为无复流组(>20%)和对照组(≤20%),采用ELISA法测定两组大鼠血清C反应蛋白(CRP)和IL-6水平,real-time PCR法测定左心室COX1、2的RNA转录水平。另用吲哚美辛、0.9%氯化钠注射液(生理盐水)对无复流大鼠进行预处理,采用颈动脉插管法测定吲哚美辛组、生理盐水组及对照组大鼠心脏收缩舒张功能及无复流面积。结果无复流大鼠血清CRP和IL-6水平较对照组升高,左心室COX1、2的RNA转录水平也高于对照组,差异均有统计学意义(均P<0.05),对照组大鼠心脏功能优于模型组,吲哚美辛组大鼠心室舒张末压低于模型组,而左室等容收缩期左心室内压力上升的最大速率和等容舒张期左心室压力下降的最大速率均较无复流模型组升高,吲哚美辛组无复流面积较模型组明显减少,差异均有统计学意义(均P<0.05)。结论 CRP、IL-6可能通过COX途径介导大鼠冠状动脉无复流现象,吲哚美辛能通过拮抗COX途径相关的炎症反应,改善大鼠冠状动脉的无复流。

Objective To investigate the effect of cyclooxygenase（COX） on no-reflow phenomenon in acute myocardial infarction（AMI）. M ethods Acute myocardial infarction was induced by ligation and reperfusion of the left anterior descending coronary artery（LAD） in Sprague Dawley（SD） rats. Thioflavin S was injected for the measurement of the no-reflow area in the left ventricle of rats; then the rats were divided into the no-reflow group and the normal-reflow group. The serum levels of C-reactive protein（CRP） and interleukin（IL）-6 were determined by ELISA after the operation. Real-time PCR was used to detect the transcription levels of the COX1, 2 in left ventricle. Indometacin was used to block cyclo-oxygenase-2 pathway. The heart rate（HR）, left ventricular end diastolic pressure（LVEDP）, positive and negative peak first derivative（±dp/dt max） were measured through carotid artery intubation by the end of balanced perfusion. Results Serum CRP and IL-6 levels in no-reflow group were significantly higher than those in normal-reflowgroup（both P〈0.05）. The expressions of COX1, 2 in left ventricle were elevated in no-reflow group compared to normal-reflow group（both P 〈0.05）. The heart functions of no-reflow group were decreased compared to normal-reflow group. LVEDP in no-reflow group was higher than that in normal-reflow group. Moreover, HR and ±dp/dt were significantly decreased in no-reflow group. With indometacin injection LVEDP and ±dp/dt of no-reflow group were significantly improved（all P 〈0.05）. Conclusion Inflammatory factors CRP and IL-6 may be involved in the no-reflow phenomenon of AMI, which may be associated with the effect of cyclooxygenase. Indometacin can block the COX pathway and decrease the no-reflowin AMI of rats.