乌司他丁对缺血再灌注大鼠心肌肿瘤坏死因子-α、白介素-8的影响

Protective effect of ulinastatin on ischemia and reperfusion of heart in rats

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 study the protective effects of different doses of ulinastatin on ischemia and reperfusion injury of heart in SD rats. METHODS Fifty SD rats were randomly divided into five groups： the normal control group（ A）, ischemia and reperfusion group（B）, high dose ulinastatin group（C）,middle dose ulinastatin group（D）, low dose ulinastatin group（E）. And the animals were killed after 40 min ischemia of heart followed by reperfusion for 2 h. TNF-α and IL-8 were detected,and apoptosis of heart muscle were observed. RESULTS After ischemia and reperfusion,the serum level of TNF-α and IL-8 remarkedly decreased,and the index of apoptosis significantly reduced. CONCLUSION Ulinastatin has dose-related protective effects on rat heart ischemia and reperfusion injury.