通心络预给药2 h对猪急性心肌梗死再灌注后心肌无再流和细胞因子变化的影响

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目的评价急性心肌梗死(AMI)猪缺血再灌注前2 h给予通心络对血清细胞因子水平和心肌无再流变化的干预效果。方法中华小型猪40只,随机分成假手术组、AMI对照组、通心络小剂量(0.1 g/kg)、中剂量(0.2 g/kg)和大剂量(0.4 g/kg)组,每组各8只。冠状动脉前降支阻断1.5 h,再灌注3 h建立AMI再灌注动物模型。各通心络治疗组于AMI缺血再灌注前2 h行灌胃给药。测定并比较各组AMI前、AMI 1.5 h、再灌注后3 h血清细胞因子水平变化。于AMI 1.5 h和再灌注3 h行心肌声学造影(myocardial contrast echocardiography,MCE),测定并比较心肌无再流面积变化。结果(1)与对照组比较,仅大剂量通心络组在AMI 1.5 h P-选择素(P-selectin)、细胞间黏附分子-1(ICAM-1)水平显著降低(均P<0.05),而再灌注后3 h P-选择素、细胞间黏附分子-1、血管细胞黏附分子-1(VCAM-1)、白细胞介素-6(IL-6)水平均显著降低(均P<0.05),白细胞介素-10(IL-10)水平显著升高(P<0.05);(2)与对照组比较,大剂量通心络能够显著缩小再灌注后3 h心肌无再流区面积[分别为(6.59±1.73)cm2、(4.68±1.53)cm2,P<0.05]。中小剂量组则差异无统计学意义。结论在AMI猪缺血再灌注前2 h予大剂量通心络可显著降低再灌注后细胞黏附和促炎症因子水平,调高抗炎症因子水平,并缩小心肌无再流面积,为临床应用提供了实验基础。 Objective To evaluate the intervention effect of Tongxinluo on serum cytokines and no-reflow in the myocardium before reperfusion of acute myocardial infarction (AMI) pigs. Methods Forty Chinese miniature pigs were randomly divided into sham operation group, AMI control group, Tongxinluo low-dose (0.1 g/kg), middle-dose (0.2 g/kg) and high-dose (0.4 g/kg) groups. 8 each. The anterior descending coronary artery was blocked for 1.5 h, and the reperfusion model was established 3 h after reperfusion. Each Tongluoluo treatment group was intragastrically administered 2 hours before AMI ischemia and reperfusion. The changes of serum cytokine levels before and after AMI, 1.5 h after AMI, and 3 h after reperfusion were measured and compared. Myocardial contrast echocardiography (MCE) was performed at 1.5 h after AMI and 3 h after reperfusion. Myocardial no-reflow area was measured and compared. Results (1) Compared with the control group, only the high-dose Tongxinluo group significantly decreased P-selectin and intercellular adhesion molecule-1 (ICAM-1) levels in AMI 1.5 hours (all P<0.05). The levels of P-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1 (VCAM-1) and interleukin-6 (IL-6) were significantly decreased at 3 h after reperfusion (all P<0.05). ), Interleukin-10 (IL-10) levels were significantly increased (P <0.05); (2) compared with the control group, high-dose Tongxinluo can significantly reduce the area of ​​myocardial reflow 3 hours after reperfusion [ They were (6.59 ± 1.73) cm2, (4.68 ± 1.53) cm2, P <0.05, respectively. In the small and medium dose group, the difference was not statistically significant. Conclusions High-dose Tongxinluo at 2 h before ischemia/reperfusion of AMI pigs can significantly reduce the levels of cell adhesion and pro-inflammatory cytokines after reperfusion, increase the levels of anti-inflammatory cytokines, and reduce the myocardial no-reflow area, providing clinical application The experimental basis.
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