Wang B, Bai M, Bai Y, Li Q
Henan College of Chinese Traditional Medicine, Zhengzhou, Henan Province, China.
Transplant Proc. 2010 Nov;42(9):3422-6. doi: 10.1016/j.transproceed.2010.09.008.
All transplanted solid organs experience some degree of ischemia-reperfusion (I-R) injury. There is some evidence that I-R injury affects remote organs. We investigated the effects of renal I-R injury on hepatic function, cytochrome P-450 enzymes, and morphology in rats.
A rat model of 1 hour of renal ischemia followed by 1, 4, or 8 hours of reperfusion. The assays included serum alanine aminotransferase (sALT) aspartate aminotransferase (sAST), cytochrome P-450 enzymes (CYP3A, CYP2E1), hepatic glutathione S-transferase (GST), glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), and myeloperoxidase (MPO) activities. In addition, we measured serum blood urea nitrogen (BUN) and serum creatinine (SCr), and renal MDA, glutathione peroxidase levels, and SOD activities. Morphological liver changes were observed by optical and electron microscopy.
sALT and sAST significantly increased after 1 hour of ischemia and 4 or 8 hours of reperfusion. Hepatic CYP3A and CYP2E1 activities were significantly decreased after 1 hour of ischemia and 1 or 4 hours of reperfusion. Hepatic GST, GSH, and SOD activities decreased after renal I-R, while MDA levels and MPO increased. Serum BUN and SCr levels significantly increased after reperfusion. Changes in renal MDA, GSH-px, and SOD activities were similar to those in the liver. The only difference between them was the peak time of injury: for the kidney, 8 hours, while for the liver, some changes appeared at 4 hours. Optical microscopy showed hepatic passive venous congestion and fatty degeneration as well as local necrosis. Transmission electronic microscope showed hepatic cell membrane was damaged, which seemed to explain some data results above. For example, the release of hepatic ALT and AST increased serum ALT and AST. More importantly, the release of neutrophil chemokine induced neutrophil accumulation in the liver, which could cause further damage.
Our findings indicated that hepatic function, cytochrome P-450 enzymes and morphology were affected by renal I-R injury. These effects seemed to be mediated in part by an imbalance of oxidant and antioxidant systems and recruitment of neutrophils to the liver.
所有移植的实体器官都会经历一定程度的缺血再灌注（I-R）损伤。有证据表明，I-R损伤会影响远处器官。我们研究了肾I-R损伤对大鼠肝功能、细胞色素P-450酶及形态的影响。
建立大鼠肾缺血1小时后再灌注1、4或8小时的模型。检测指标包括血清丙氨酸氨基转移酶（sALT）、天冬氨酸氨基转移酶（sAST）、细胞色素P-450酶（CYP3A、CYP2E1）、肝谷胱甘肽S-转移酶（GST）、谷胱甘肽（GSH）、丙二醛（MDA）、超氧化物歧化酶（SOD）和髓过氧化物酶（MPO）活性。此外，我们还检测了血清尿素氮（BUN）和血清肌酐（SCr），以及肾MDA、谷胱甘肽过氧化物酶水平和SOD活性。通过光学显微镜和电子显微镜观察肝脏形态学变化。
缺血1小时及再灌注4或8小时后，sALT和sAST显著升高。缺血1小时及再灌注1或4小时后，肝CYP3A和CYP2E1活性显著降低。肾I-R后，肝GST、GSH和SOD活性降低，而MDA水平和MPO升高。再灌注后血清BUN和SCr水平显著升高。肾MDA、GSH-px和SOD活性的变化与肝脏相似。它们之间唯一的区别是损伤的峰值时间：肾脏为8小时，而肝脏的一些变化出现在4小时。光学显微镜显示肝脏出现被动性静脉淤血、脂肪变性以及局部坏死。透射电子显微镜显示肝细胞膜受损，这似乎解释了上述一些数据结果。例如，肝ALT和AST的释放增加了血清ALT和AST。更重要的是，中性粒细胞趋化因子的释放诱导中性粒细胞在肝脏中积聚，这可能导致进一步损伤。
我们的研究结果表明，肾I-R损伤会影响肝功能、细胞色素P-450酶及形态。这些影响似乎部分是由氧化和抗氧化系统失衡以及中性粒细胞向肝脏募集介导的。
