甲状腺激素对大鼠肝脏缺血再灌注损伤的保护作用  

The protective effect of thyroid hormone on hepatic ischemia-reperfusion injury in rat

作　　者：李长贤[1] 李相成[1] 陈杰[1] 许永华[1] 张斌[1] 

机构地区：[1]南京医科大学第一附属医院肝脏移植中心,江苏南京210029

出　　处：《南京医科大学学报（自然科学版）》2010年第1期50-53,91,共5页Journal of Nanjing Medical University(Natural Sciences)

基　　金：江苏省"科教兴卫工程"医学重点人才基金(RC2007056)

摘　　要：目的:探讨甲状腺激素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64只健康雄性SD大鼠随机分成4组:正常对照组(S组),缺血再灌注组(IR组),缺血预处理组(IPC)组,甲状腺激素干预组(T3组)。缺血1h再灌注6h、24h后,检测血清丙氨酸转氨酶(ALT)、天门冬氨酸转氨酶(AST)、肿瘤坏死因子(TNF-α)水平以及肝脏组织超氧化物歧化酶(SOD)的活性及丙二醛(MDA)、还原型谷胱甘肽(GSH)的含量,病理切片HE染色和免疫组化方法分别检测肝脏组织的病理改变和肝细胞核因子-κB(NF-κB)阳性表达。结果:肝脏缺血再灌注后,IR组的ALT、AST水平及MDA、TNF-α、NF-κB阳性表达明显高于S组,GSH含量、SOD活性明显下降(P<0.01),肝组织病理损伤较S组严重,T3组、IPC组均能改善以上情况(P<0.01),而T3组及IPC组之间无明显差异(P>0.05)。结论:甲状腺激素和缺血预处理一样对大鼠肝脏缺血再灌注损伤具有一定的保护作用。其机制可能通过减少氧自由基的产生及减轻脂质过氧化反应,降低TNF-α的表达和抑制NF-κB的活化来实现。Objective：To investigate the protective effect of thyroid hormone on hepatic ischemia-reperfusion injury and its possible mechanism in rat.Methods：The model of 70% hepatic ischemia-reperfusion was established in rat.Sixty-four healthy male SD rats were randomly divided into 4 groups.S：sham operation group;IR：ischemia-reperfusion group;IPC：ischemic preconditioning group;T3：thyroid hormone treatment group.After 6 h and 24 h of reperfusion,aspartate aminotransferase（AST）,alanine aminotransferase（ALT） and tumor necrosis factor alpha（TNF-α） levels in the serum were measured;the superoxide dismutase（SOD） activity,levels of malondialdehyde（MDA） and glutathione（GSH） in the hepatic tissue were detected.Histologic changes was observed in HE staining, and the expression of NF-κB in liver cells was evaluated by immunohistochemistry.Results：After ischemia-reperfusion,compared with S group,IR group showed higher levels of ALT,AST,MDA,TNF-αand NF-κB and more obviously injury of liver tissue,but the activity of SOD and GSH decreased.After treatment of thyroid hormone and ischemic preconditioning,all above abnormal parameters were retrieved remarkably（P 〈 0.01）.but there are no obvious difference between IPC group and T3 group（P 〉 0.05）.Conclusion：Thyroid hormone,as well as ischemic preconditioning,has a protection against hepatic ischemia-reperfusion injury in rat.The mechanism of protection may be associated with its scavenging of radical,inhibition of lipid peroxidation,decrease of TNF-α level and suppression of NF-κB activation.

关 键 词：缺血再灌注损伤 甲状腺激素 缺血预处理 核因子-ΚB 肿瘤坏死因子 

分 类 号：R335.2[医药卫生—人体生理学]