特丁基对苯二酚预处理减轻大鼠肝脏缺血再灌注损伤

Tert-Butylhydroquinone Alleviates Hepatic Ischemia Reperfusion Injury in Rats Through Nrf2 Pathway

目的:探究特丁基对苯二酚(tBHQ)对大鼠肝脏缺血再灌注损伤的保护作用及机制。方法:24只大鼠随机分为4组,即假手术组(SD组)、缺血再灌注组(ID组)、tBHQ假手术组(ST组)和tBHQ缺血再灌注组(IT组)。tBHQ溶液分3次每次间隔12h手术前尾静脉注射于大鼠体内。通过蛋白质印迹法(Western Blot)和聚合酶链式反应(PCR)检测核因子NF-E2相关因子(Nrf2)和抗氧化反应原件(ARE)的表达程度。应用苏木素-伊红(HE)染色检测各组肝脏损伤程度,采用比色法检测血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)浓度,ELISA法测定肝组织中超氧化物歧化酶(SOD)、丙二醛(MDA)水平。结果:应用tBHQ后,大鼠肝脏Nrf2及ARE表达明显上升。相比于ID组,IT组血清AST、ALT,肝组织MDA水平降低,SOD水平上升,结果均有统计学意义(P<0.05)。组织染色结果显示,ID组有大量炎性细胞侵润和肝细胞坏死,IT组组织损伤程度明显减轻。结论:tBHQ通过促进Nrf2及其下游ARE的表达,起到减轻大鼠肝脏缺血再灌注损伤的作用。

Objective： To explore the protective function of tert-butylhydroquinone （tBHQ） on rat liver ischemia-reperfusion injury and its mechanism. Methods： Twenty-four adult male rats were ran- domly divided into four groups： ①SHAM＋DMSO group（SD）; ②Ischemia reperfusion injury （IRI）＋DMSO group（ID） ; ③SHAM＋tBHQ group（ST）; ④IRI＋tBHQ group（IT）. The tBHQ were administrated into rats at intervals of 12 h by three tail vein injections. Western blot analy- sis and lluorescenee quantitative PCR were used to examine protein expression of Nrf2, HO-1 andARE, respectively. The concentration of MDA and SOD activity were determined, and the de- gree of liver injury was tested by HE. Results： Compared with those in SD group, AST, ALT, Nrf2 expression and MDA content were significantly raised in ID group, while SOD activity was dramatically declined. Meanwhile, in IT group, tBHQ alleviated hepatocellular damage, promo- ted NQO1, GSTs and GCL expression, and regained redox homeostasis in comparison with ID group. Conclusion： TBHQ exerted effective antioxidant effects on hepatic IRI, and tBHQ would be a new potential therapeutic measure for preventing hepatic IRI during liver surgery.