Trx2、GSH和GSH-PX与大鼠肝移植术后肾损伤修复的相关性研究  

Correlation Analysis among Trx2, GSH, GSH-PX and Repair of Kidney Injury Induced by Rat Liver Transplantation

作　　者：原冬冬[1] 葛缅[1] 孙国亮[1] 张政[1] 池信锦[1] 黑子清[1] 

机构地区：[1]中山大学附属第三医院麻醉科,广东广州510630

出　　处：《中山大学学报（医学科学版）》2013年第5期666-671,共6页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：国家自然科学基金(81170449);广东省中医药局课题(20121143)

摘　　要：【目的】探讨线粒体型硫氧还蛋白(Trx2),谷胱甘肽(GSH)和谷胱甘肽过氧化物酶(GSH-PX)对肝移植术后急性肾损伤的保护作用。【方法】建立大鼠肝移植模型,将雄性SD大鼠35只,随机均分为假手术组(n=7)和移植后4 h组(n=7),移植后8 h组(n=7),移植后16 h组(n=7)和移植后24 h组(n=7)。假手术组只进行开腹和血管的分离,各移植组接受自体肝移植。观察大鼠自体肝移植后不同时期肾脏病理、活性氧水平、Trx2表达、乳酸脱氢酶(LDH)、谷胱甘肽(GSH)和谷胱甘肽过氧化物酶(GSH-PX)的活性。【结果】肝移植术后8h肾脏损伤最为严重,移植术后24 h肾脏损伤有所恢复。肝移植术后4 h开始,肾脏·OH、H2O2、MDA和LDH的含量明显增加,逐渐达到最高水平,术后24 h逐渐恢复正常。而具有保护作用的GSH以及GSH-PX的含量在肝移植术后4 h即开始明显下降,术后24 h逐渐恢复至正常水平。肾脏Trx2的表达在肝移植术后4 h反应性的增高,术后8 h达到最高峰,而后逐渐下降。相关性分析显示,肝移植术后肾脏GSH、GSH-PX的含量与肾损伤病理评分呈负相关(P<0.01);肾脏Trx2蛋白表达与肾损伤病理评分呈正相关(P<0.05)。【结论】肝移植术后4 h即可发生明显的肾损伤,术后8 h最为明显,而后逐渐恢复。其损伤的严重程度与GSH和GSH-PX的含量呈负相关;与Trx2的表达呈正相关,Trx2表达的增加有利于抗氧化酶合成,减轻肝移植术后的急性肾损伤。[Objective] To investigate the effects of Trx2, GSH, and GSH-PX on acute kidney injury （AKI） induced by rat orthotopic liver transplantation （OLT）. [Methods] Thirty-five Sprague-Dawley （SD） rats were divided into 5 groups： sham group, and other 4 groups ： 4 h, 8 h, 16 h, and 24 h after orthotopic liver transplantation groups. Rats in sham group only suffered from the process of laparotomy and vascular separation, while in other groups all subjected to OLT. Kidney pathological changes after OLT and levels of -OH, H202, MDA, LDH were observed. GSH, GSH-PX and expression of Trx2 were detected to explore their protection effects on AKI induced by OLT. [ Results ] Eight hours after OLT, kidney pathological damage was most serious. From 4 hours after OLT, levels of OH, H202, MDA, LDH increased obviously, and recovered to the normal level until 24 hours after OLT. By contrast, both GSH and GSH-PX decreased from 4 hours after OLT and came back to the normal level at 24 hours after OLT. Expression of Trx2 increased from the time point of 4 hours after OLT and reached the top at 24 hours after OLT, then, declined gradually. Correlation analysis showed that there were negative correlations between kidney damage and levels of GSH and GSH-PX （P 〈 0.01）, but positive correlations between kidney damage and Nrf2 expression （P 〈 0.05）. [Conclusion] AKI induced by OLT changed dynamically. Eight hours after OLT, AKI was most obvious and then, recovered gradually. Kidney damage was relative with GSH and GSH-PX decrease. Increase of Trx2 expression could protect against AKI induced by OLT.

关 键 词：肝移植 急性肾损伤 线粒体型硫氧还蛋白 谷胱甘肽 谷胱甘肽过氧化物酶 

分 类 号：R692.5[医药卫生—泌尿科学]