乌司他丁对大鼠缺血再灌注心肌细胞的保护机制

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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(CK-MB)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。“,”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+Ulinas-tain 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 signifi-cantly, 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 sig-nificant (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.
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