依达拉奉对大鼠肝脏缺血再灌注损伤保护作用的实验研究

Experimental studies on the protective effect of Edaravone against hepatic ischemia-reperfusion injury in rat

目的:探讨依达拉奉对大鼠肝脏缺血再灌注损伤的保护作用及其可能作用机制。方法:建立大鼠70%的肝脏缺血再灌注模型,将24只SD雄性健康大鼠随机分成3组(n=8):空白对照组(S组),缺血再灌注组(IR组)和依达拉奉干预组(ED组)。再灌注2h后检测血清谷丙转氨酶(ALT)、谷草转氨酶(AST)水平以及肝脏组织超氧化物歧化酶(SOD)、髓过氧化物酶(MPO)的活性及丙二醛(MDA)的含量,并用免疫组化方法和病理切片HE染色方法分别检测肝细胞中的核因子-κB(NF-κB)阳性表达率和肝脏组织的病理改变。结果:肝脏缺血再灌注后,IR组的ALT、AST水平及MDA、MPO、NF-κB阳性表达率明显高于S组(P<0.01),SOD活性明显下降(P<0.01),肝组织病理损伤较S组重,依达拉奉能改善以上情况。结论:依达拉奉对大鼠肝脏缺血再灌注损伤有保护作用,其机制可能通过清除氧自由基,抑制脂质过氧化和抑制NF-κB的活化来实现。

Objective：To investigate the protective effect of Edaravone against hepatic; ischemia-reperfusion injury in rat and clarify its possible mechanism. Methods：The model of 70% hepatic ischemia-reperfusion was established in SD male rat. Twenty four healthy rats were randomly divided into 3 groups,S： sham operation group（n = 8）,IR：ischemia-reperfusion group（n = 8）,ED：Edaravone treatment group （n = 8）. After 2 hours of reperfusion,the enzyme levels in serum were examined including ALT and AST. The SOD, MDA and MPO in liver tissues were measured. The expression of NF-KB in liver cell was determined in immunohistochemistry, and histologic changes was observed in HE staining. Results：After ischemia-reperfusion, the levels of ALT, AST, MDA, the activity of MPO and NF-KB expression in IR group was significantly higher than those in S group, The injury of liver tissue in IR group was more obviously, but the activity of SOD was decreased. After treatment of Edaravone, the all above abnormal parameters were retrieved remarkably （P 〈 0.01）. Conclusion：This study suggests that Edaravone has a protective effect on liver against ischemia-reperfusion injury in rat. The mechanism of protection may be related to its scavenging of radical,inhibiting of lipid peroxidation,and suppressing of NF-KB activation,