摘要
【目的】探讨线粒体硫氧还蛋白(Trx2)和抗氧化能力在原位自体原位肝移植(AOLT)大鼠后24 h内肝脏组织动态变化。【方法】将40只雄性SD大鼠随机均分为假手术组(Group S,n=8)、肝移植后4 h组(LTR 4h group,n=8),肝移植后8 h组(LTR 8h group,n=8),肝移植后16 h组(LTR 16h group,n=8)和肝移植后24 h组(LTR 24h group,n=8)。S组只进行开腹和血管的分离,各肝移植组接受自体原位肝移植(AOLT),光镜下观察各组大鼠肝脏病理学改变,Suzuki病理学评分改变,实验室检测活性氧水平、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和谷胱甘肽(GSH)活性、总抗氧化能力(TOC)变化、及Western Blot法检测Trx-2的蛋白表达的变化。【结果】自体肝移植引起了大鼠明显的肝脏损伤,组织病理评分在移植后4 h明显升高并达峰值,持续到移植后24 h(P<0.05,vs.group S),但24 h较4 h有明显改善(P<0.05 vs.group LTR4h);O2.、.OH和MDA的生成在4 h到16 h增加明显(1.6～2.0倍),MDA水平发生与之一致的时间变化(P<0.05 vs.group S);抗氧化酶活性在肝移植后4 h和8 h下降明显,SOD、CAT和GSH活性下降达30%(P<0.05 vs.group S),TOC活性下降达70%(P<0.01 vs.group S)。而相对氧化/抗氧化指标来讲,移植后肝脏组织内Trx-2蛋白表达增高的速度较慢,4 h开始表达增加(P<0.05 vs.group S),而直到24 h才达到蛋白表达峰值(～2.0倍)。【结论】移植后肝脏发生损伤,并逐渐加重而后逐渐恢复,损伤程度与活性氧水平和抗氧化酶活性变化趋势相一致;Trx-2的表达上调有利于抗氧化酶合成和提高抗氧化能力。
[ Objective] Mitochondria thioredoxin （thioredoxin 2） and its modulated antioxidant enzymes compose the critical endogenous antioxidant system in human body to scavenge reactive oxygen species （ROS）. We aimed to investigate the patterns of alteration to thioredoxin2 expression and antioxidants capacity in liver tissue during 24 h after liver transplantation in rats. [ Methods ] Forty Sprague Dawley （SD） rats were randomly divided into sham group, and 4, 8, 16, and 24 h after autologous orthotopic liver transplantation （AOLT） group. Rats in sham group only suffered from the process of laparotomy and vascular separation, while in other groups all subjected to AOLT. Liver tissues were collected for detection of pathological changes by light microscope, Trx2 expressions by Western blot, and changes of ROS levels and activities of antioxidants. [ Results ] AOLT resulted in severe liver injury in rats during 24 hours after reperfusion manifested as significant elevations in liver pathological scores as early as 4 hours after AOLT. There was also obvious oxidative damage that was evidenced with 1.6 to 2.0 fold increases of 02＂ or -OH and MDA levels, accompanied with significant decreases （-30%） in the activity of SOD or catalase and a dramatic （~70%） decrease in level of TOC at 4 h and 8 h （P 〈 0.01 vs. Sham group）. All the parameters restored gradually at 16 and 24 hours after AOLT. The expression of Trx2 in liver increased significantly as early as 4 hours and peaked at 24 hours after AOLT （~2.0 fold） （P 〈 0.05 vs. Sham group）. [Conclusion] AOLT could result in severe liver injury, the extent of which coincidence with the oxidant/antioxidant system statemanifested as exacerbating first and then alleviating gradually. Up-regulation of Trx2 expression was beneficial to synthesizing antioxidants and further enhancing the antioxidant capacity of liver tissue subjected to ischemia! reperfusion injury during AOLT.
出处
《中山大学学报（医学科学版）》
CAS
CSCD
北大核心
2012年第6期775-780,共6页
Journal of Sun Yat-Sen University:Medical Sciences
基金
广州市科技计划项目(2011J4300056)
