替格瑞洛对急性心肌梗死大鼠心肌组织中ROS、TNF-α及IL-6含量的影响

Effect of Ticagrelor on the Levels of ROS,TNF-alpha and IL-6 in the Myocardium of Rats with Acute Myocardial Infarction

目的观察替格瑞洛对急性心肌梗死大鼠心肌组织中ROS、TNF-α、IL-6含量的影响。方法 48只健康成年雄性SD大鼠,随机分为对照组、假手术组(sham组)和心肌梗死模型组(AMI组)以及心肌梗死后口服替格瑞洛组(AMI+Ti组),AMI组及AMI+Ti组大鼠开胸并结扎冠状动脉前降支建立心肌梗死模型。结扎成功6、24和48h后无痛处死大鼠获取心肌组织;对照组大鼠不做任何处理;假手术组大鼠开胸冠状动脉穿线但不结扎冠状动脉;四组大鼠均无痛处死大鼠并获取心肌组织;使用比色法测定心肌组织中ROS(O2-和OH-)含量,使用Western blot检测心肌组织TNF-α、IL-6表达量。结果同对照组相比,sham组大鼠心肌组织中ROS含量(O2-和OH-)均无明显变化(P均>0.05),在冠脉结扎6、24和48h的时间点,AMI组大鼠、AMI+Ti组大鼠心肌组织中ROS含量均高于sham组(P均<0.05),冠脉结扎6、24和48h时AMI+Ti组大鼠心肌组织中ROS含量均明显低于AMI组大鼠对应时间点ROS含量(P均<0.05);同对照组相比,sham组大鼠心肌组织中TNF-α、IL-6表达量均无明显变化(P均>0.05),冠脉结扎6、24和48h AMI组大鼠、AMI+Ti组大鼠心肌组织中TNF-α、IL-6表达量均高于sham组大鼠对应时间点TNF-α、IL-6表达量(P均<0.05),冠脉结扎6、24和48h时AMI+Ti组大鼠心肌组织中TNF-α、IL-6表达量均低于AMI组大鼠对应时间点心肌组织中TNF-α、IL-6表达量(P均<0.05)。结论替格瑞洛可抑制AMI大鼠心肌组织氧化应激反应而减少ROS含量并降低心肌组织中TNF-α和IL-6水平而发挥心肌保护作用。

Objective To observe the effect of Ticagrelor on the levels of ROS,TNF-alpha and IL-6 in the myocardium of rats with acute myocardial infarction. Methods Totally 48 healthy adult male SD rats were randomly divided into control group,sham operation group（group sham） and myocardial infarction model group（group AMI）and AMI＋Ti group（group AMI＋Ti）after myocardial infarction. The myocardial infarction model was established in group AMI and group AMI＋Ti by ligating the anterior descending branch of coronary artery. Myocardial tissue was obtained without pain after 6,24 and 48 h ligature in rats. The rats in the control group did not do any treatment. The rats in the sham operation group had the coronary artery thread after opening the chest and without the coronary artery ligation. Myocardial tissue was obtained in the above fourgroups after the rats were killed without pain. The level of ROS in myocardial tissue was determined by colorimetry method. The levels of TNF-alpha and IL-6 were detected using western blot. Results Compared with the control group,there was no significant change in the level of ROS（O-2 and OH-）in the myocardial tissue of the sham group（P〉0.05）. After coronary artery ligation for 6 h,24 h and 48 h,ROS levels in rats of group AMI and AMI＋Ti were higher than the corresponding time points in sham rats（P〈0.05）. After coronary artery ligation for 6 h,24 h and 48 h,ROS level in rats of AMI＋Ti group was significantly lower than that in group AMI（P〈0.05）. The expression of TNF-α and IL-6 in myocardial tissue of rats in sham group had no obvious change compared with the control group（P〉0.05）. After coronary artery ligation for 6 h,24 h and 48 h,TNF-α and IL-6 in rats of group AMI and AMI＋Ti were obviously higher than thoese in sham rats（P〈0.05）. TNF-α and IL-6 in rats of AMI＋Ti group were significantly lower than those in AMI group rats（P〈0.05）. Conclusion Ticagrelor can reduce oxidative stress in myocardial tissue of AMI rats and reduce the content of ROS. It also can decrease TNF-alpha and IL-6 levels in myocardial tissue and plays a role in myocardial protection.