Zeng X-P, Li X-J, Zhang Q-Y, Liu Q-W, Li L, Xiong Y, He C-X, Wang Y-F, Ye Q-F
Wuhan University, Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, China.
Research Center of National Health Ministry on Transplantation Medicine Engineering and Technology, The 3rd Xiangya Hospital of Central South University, Changsha, China.
Transplant Proc. 2017 Mar;49(2):366-372. doi: 10.1016/j.transproceed.2016.12.008.
Hepatic ischemia/reperfusion (I/R) injury is a serious complication that occurs in surgical operations such as hepatectomy and liver transplantation. NF-E2-related factor 2 (Nrf2) is a transcription factor that has been proven against inflammatory and oxidative injury. Tert-butylhydroquinone (tBHQ), a widely used Nrf2 activator, is a common food preservative. In this study, we attempt to investigate the potential protective role of tBHQ in hepatic I/R injury.
Twenty adult male rats were randomly divided into four groups: (1) sham+vehicle group; (2) I/R+vehicle group; (3) sham+tBHQ group; and (4) I/R+tBHQ group. The vehicle or tBHQ was divided into three injections at intervals of 12 hours in a model of hepatic I/R injury. Fluorescence quantitative polymerase chain reaction and Western blot analysis were used to examine Nrf2 mRNA and protein expression. The concentrations of malondialdehyde and superoxide dismutase activity were accessed, respectively.
Compared with the sham+vehicle group, Nrf2 expression, malondialdehyde, content and serum alanine aminotransferase were significantly increased in the I/R+vehicle group, whereas superoxide dismutase activity was significantly decreased. However, in the I/R+tBHQ group, tBHQ ameliorated tissue damage; promoted glutathione-S-transferase, quinine oxidoreductase 1, and glutamate cysteine ligase inductions; and regained redox homeostasis in comparison with the I/R+vehicle group. Furthermore, the present study indicated that preconditioning with tBHQ suppressed the I/R-induced increase in the apoptotic protein levels of caspase-3, as well as the I/R-induced decrease in the levels of anti-apoptotic protein bcl-2.
t-BHQ exerted potent anti-inflammatory effects in I/R-induced liver injury, and tBHQ would be a new effectively therapeutic measure for preventing hepatic I/R injury during liver surgery.
肝缺血/再灌注（I/R）损伤是肝切除术和肝移植等外科手术中发生的一种严重并发症。核因子E2相关因子2（Nrf2）是一种转录因子，已被证明可抵抗炎症和氧化损伤。叔丁基对苯二酚（tBHQ）是一种广泛使用的Nrf2激活剂，是一种常见的食品防腐剂。在本研究中，我们试图探究tBHQ在肝I/R损伤中的潜在保护作用。
将20只成年雄性大鼠随机分为四组：（1）假手术+赋形剂组；（2）I/R+赋形剂组；（3）假手术+tBHQ组；（4）I/R+tBHQ组。在肝I/R损伤模型中，赋形剂或tBHQ每隔12小时分三次注射。采用荧光定量聚合酶链反应和蛋白质免疫印迹分析检测Nrf2 mRNA和蛋白表达。分别检测丙二醛浓度和超氧化物歧化酶活性。
与假手术+赋形剂组相比，I/R+赋形剂组Nrf2表达、丙二醛含量及血清丙氨酸氨基转移酶显著升高，而超氧化物歧化酶活性显著降低。然而，与I/R+赋形剂组相比，在I/R+tBHQ组中，tBHQ减轻了组织损伤；促进了谷胱甘肽-S-转移酶、醌氧化还原酶1和谷氨酸半胱氨酸连接酶的诱导；并恢复了氧化还原稳态。此外，本研究表明，tBHQ预处理可抑制I/R诱导的半胱天冬酶-3凋亡蛋白水平升高，以及I/R诱导的抗凋亡蛋白bcl-2水平降低。
t-BHQ对I/R诱导的肝损伤具有强大的抗炎作用，tBHQ将成为预防肝脏手术中肝I/R损伤的一种新的有效治疗措施。
