乌司他丁对大鼠缺血再灌注心肌细胞的保护机制

目的观察乌司他丁对心肌缺血再灌注后大鼠心肌细胞的保护机制。方法采用垫扎球囊法结扎冠状动脉制作心肌缺血再灌注的动物模型,30只大鼠随机分为三组：假手术组（n=10）、缺血/再灌注（I/R）组（n=10）和I/R＋乌司他丁组（n=10）。检测三组心肌组织谷胱甘肽（GSH）、丙二醛（MDA）及血清标志物肌酸激酶同工酶（CKMB）含量,采用TTC染色确定心肌梗死及缺血范围,并用Western-blot测定炎症因子白细胞介素-6（IL-6）、IL-8的表达。结果与假手术组比较,I/R组中反映氧化损伤程度的MDA明显升高（4.13±3.27）nmol/L比（11.13±2.13）nmol/L],CK-MB也升高（15.21±6.24）U/L比（2752.21±1276.36）U/L],GSH则明显降低（241.42±3.28）mg/L比（184.26±2.14）mg/L],差异均有高度统计学意义（P〈0.01）;与I/R组比较,I/R＋乌司他丁组MDA（8.25±4.26）nmol/L]、CK-MB（1873.24±621.43）U/L]含量降低,差异有统计学意义（P〈0.05）。I/R＋乌司他丁组梗死面积（12.27±4.26）%]小于I/R组（17.12±3.18）%],差异有统计学意义（P〈0.05）。假手术组IL-6、IL-8水平较低（0.412±0.550）、（0.132±0.071）],缺血再灌注后,I/R组IL-6、IL-8表达升高（1.785±0.720）、（0.926±0.247）],差异有高度统计学意义（P〈0.01）;与I/R组比较,I/R＋乌司他丁组炎性因子IL-6、IL-8水平下降（1.102±0.780）、（0.672±0.240）],差异有统计学意义（P〈0.05）。结论乌司他丁具有抗心肌缺血再灌注损伤作用,其机制可能是通过下调IL-6和IL-8介导的炎性反应而实现。

Protection mechanism of Ulinastain on heart ischemia/reperfusion injury in rats

Objective To observe the protection mechanism of Ulinastain on heart ischemia/reperfusion injury in rats.Methods Experimental model was established by ligation of coronary artery with PTCA balloon, 30 Wistar rats were randomly divided into three groups： sham operation group（n=10）; ischemia/reperfusion（I/R） group（n=10）; I/R＋Ulinastain group（n=10）. The GSH and MDA of cardiac muscle tissues, and the serum biomarkers CK-MB in three groups were detected; ischemic and infarct areas in three groups were measured by TCC dyeing; the expression of IL-6 and IL-8 were analyzed by Western-blot analysis. Results Compared with sham operation group, the level of MDA which reflect the degree of oxidative damage in I/R group increased significantly （4.13±3.27）nmol/L vs（11.13±2.13）nmol/L],and the CK-MB was increased （15.21±6.24） U/L vs（2752.21±1276.36） U/L], the value of GSH was decreased significantly, the differences were statistically significant（P〈0.01）; compared with I/R group, MDA of I/R＋Ulinastain group（8.25±4.26） nmol/L], CK-MB （1873.24 ±621.43） U/L] decreased, the differences were statistically significant（P〈0.05）. Infarction area of I/R＋Ulinastain group （12.27±4.26）%] was lower than that of I/R group （17.12±3.18）%], the difference was statistically significant（P〈0.05）; the levels of IL-6 and IL-8 in sham operation group （0.412±0.550）,（0.132±0.071）] were lower, after ischemia reperfusion, the levels of IL-6 and IL-8 in I/R group （1.785±0.720）,（0.926±0.247）] was increased, the differences were statistically significant（P〈0.01）; compared with I/R group, the level of IL-6 and IL-8 in I/R＋Ulinastain group （1.102±0.780）,（0.672±0.240）] was decreased, the differences were statistically significant（P〈0.05）. Conclusion Ulinastain may protect myocardium from ischemia reperfusion injury by modulating the expression of IL-6 and IL-8 proteins and inhibiting inflammation.