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目的:探讨不同剂量乌司他丁在心肌缺血再灌注损伤(IRI)时的保护作用。方法:将50只雄性SD大鼠随机分为正常对照组(A组);单纯缺血再灌注组(B组),尾静脉注射生理盐水1mL.(100g)-1;乌司他丁高剂量组(C组),尾静脉注射乌司他丁50 000U.kg-1;乌司他丁中剂量组(D组),尾静脉注射乌司他丁30 000U.kg-1;乌司他丁低剂量组(E组),尾静脉注射乌司他丁10 000U.kg-1。采用左冠状动脉前降支结扎开放建立心肌缺血再灌注损伤模型,进行特定条件的缺血再灌注后取出心脏,测定心肌白介素-8(IL-8)、肿瘤坏死因子-α(TNF-α)的含量;末端脱氧核糖核苷酸转移酶介导的dUTP缺口末端标记法(Tunel法)检测细胞凋亡。结果:单纯缺血再灌注组较其他组心肌组织中IL-8和TNF-α含量明显降低,差异有显著性(P<0.01);组间比较,低剂量组、中剂量组、高剂量组差异有显著性(P<0.05)。单纯缺血再灌注组与正常对照组相比心肌细胞凋亡指数值显著升高,差异均有统计学意义(P<0.01)。而相对于单纯缺血再灌注组,乌司他丁各组心肌细胞凋亡指数较单纯缺血再灌注组明显降低(P<0.01),组间比较,低剂量组、中剂量组、高剂量组之间差异有统计学意义(P<0.01)。结论:乌司他丁预处理对缺血再灌注的心肌有明显保护作用且与剂量呈正相关。
Objective: To investigate the protective effect of ulinastatin at different doses on myocardial ischemia-reperfusion injury (IRI). Methods: Fifty male Sprague-Dawley rats were randomly divided into normal control group (group A), simple ischemia-reperfusion group (group B), normal saline 1mL (100g) -1, ulinastatin high dose Group C (group C). The ulinastatin 50 000 U.kg-1 was given to the caudal vein and the low dose ulinastatin group D (group D). The ulinastatin 30 000 U.kg- Low dose group (group E), ulinastatin 10 000U.kg-1 was injected through tail vein. The model of myocardial ischemia-reperfusion injury was established by ligation of the left anterior descending coronary artery (LADC), and then the heart was removed under certain conditions of ischemia-reperfusion. The levels of interleukin-8 (IL-8), tumor necrosis factor- ); The apoptosis was detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (Tunel method). Results: The levels of IL-8 and TNF-α in myocardial ischemia-reperfusion group were significantly lower than those in other groups (P <0.01). Compared with low-dose group, middle dose group, high dose group The difference was significant (P <0.05). Compared with the normal control group, the apoptotic index of myocardial ischemia / reperfusion group was significantly increased, the difference was statistically significant (P <0.01). However, compared with the ischemia-reperfusion group, the apoptotic index in the ulinastatin group was significantly lower than that in the ischemia / reperfusion group (P <0.01). Compared with the ischemia-reperfusion group, the apoptotic index in the low- The difference between the groups was statistically significant (P <0.01). Conclusion: Ulinastatin preconditioning has a significant protective effect on myocardial ischemia-reperfusion and is positively correlated with the dosage.