论文部分内容阅读
目的:探讨趋化因子受体5(CCR5)抗体对大鼠心肌缺血再灌注损伤的保护作用及其可能的作用机制。方法:将48只雄性大鼠随机分为4组(每组12只):假手术组(S组)、模型对照组(C组)、CCR5抗体组(T组)和缺血预处理组(I组)。建立体内急性心脏缺血再灌注损伤模型,S组不结扎冠状动脉,其余3组结扎大鼠左前降冠状动脉30 min后再灌注2 h。S组开胸后经颈外静脉给予无水乙醇0.1 ml,C组于再灌注前经颈外静脉给予无水乙醇0.1 ml,T组以相同方式按0.2μg/g给予等体积CCR5抗体,I组于再灌注前先给予左前降冠状动脉缺血5 min再灌注5 min 2个循环、缺血10 min再灌注10 min 1个回合。术中监测心电图及血流动力学指标变化;术后伊文蓝-TTC、血清中肌酸激酶(CK)的活性、肿瘤坏死因子(TNF-α)的水平和各组局部受损心肌中髓过氧化物酶(MPO)的活性;使用免疫组化SABC法测定组织细胞间黏附分子-1(ICAM-1)和NF-κB的表达情况以及RT-PCR法测定ICAM-1 mRNA的表达情况。结果:与S组相比,再灌注2 h后C组左室内压峰值和左室内压上升最大速率、左室内压下降最大速率明显下降,CK及MPO活力、TNF-α的水平明显升高,ICAM-1、ICAM-1 mR-NA、NF-κB在组织中的表达显著增加;与C组相比,T组及I组血流动力学显著改善,心肌梗死面积和ICAM-1、ICAM-1 mRNA、NF-κB在组织中的表达明显降低。结论:CCR5抗体可以通过抑制细胞因子TNF-α从而阻止NF-κB的早期活化而抑制ICAM-1表达、减少白细胞的黏附聚集从而对缺血再灌注心肌起到保护作用。
Objective: To investigate the protective effect of chemokine receptor 5 (CCR5) antibody on myocardial ischemia-reperfusion injury in rats and its possible mechanism. Methods: Forty eight male rats were randomly divided into 4 groups (12 in each group): sham operation group (S group), model control group (C group), CCR5 antibody group (T group) and ischemic preconditioning group Group I). The model of acute myocardial ischemia-reperfusion injury in vivo was established. In the S group, the coronary arteries were not ligated and the left anterior descending coronary artery was ligated in the other three groups for 30 min before reperfusion for 2 h. In group S, 0.1 ml of absolute ethanol was given via the external jugular vein after thoracotomy. 0.1 ml of absolute ethanol was given via external jugular vein before reperfusion in group C, and equal volume of CCR5 antibody was administered at 0.2 μg / g in group T Before reperfusion, the rats were given 2 cycles of 5 minutes of left anterior descending coronary artery ischemia followed by 5 minutes of reperfusion and 10 minutes of reperfusion 10 minutes after reperfusion. Intraoperative monitoring of electrocardiogram and hemodynamic parameters; postoperative Evans blue-TTC, serum creatine kinase (CK) activity, tumor necrosis factor (TNF-α) levels and each group of locally damaged myocardial myeloid (MPO). The expression of intercellular adhesion molecule-1 (ICAM-1) and NF-κB was detected by immunohistochemical SABC method and the expression of ICAM-1 mRNA by RT-PCR. Results: Compared with group S, the peak pressure of left ventricular pressure and the maximum rate of left ventricular pressure increase, the maximum rate of left ventricular pressure drop, the activity of CK and MPO and the level of TNF-α in group C were significantly increased 2 h after reperfusion, The expression of ICAM-1, ICAM-1 mR-NA and NF-κB in the tissues increased significantly. Compared with group C, the hemodynamics of group T and group I were significantly improved. The area of myocardial infarction and the expression of ICAM- 1 mRNA, NF-κB expression in the organization was significantly reduced. CONCLUSION: CCR5 antibody can inhibit ICAM-1 expression and decrease adhesion and aggregation of leukocytes by inhibiting the activation of cytokines TNF-α to prevent early activation of NF-κB, thereby protecting myocardium against ischemia-reperfusion.