Tsai J L, King K L, Chang C C, Wei Y H
Department of Technology for Medical Sciences, Kaohsiung Medical College, Taipei, Taiwan, Republic of China.
Biochem Int. 1992 Oct;28(2):205-17.
The general objective of this study was to examine the relationship between mitochondrial respiratory function and liver regeneration in the rat. The role that free radicals may play in the process was also evaluated. It was found that the respiratory control and ADP/O ratios were concomitantly decreased to the lowest level at 6 hr after hepatectomy and gradually recovered thereafter. Both ratios were significantly increased at 48 hr and quickly reached plateau levels. Assays of mitochondrial respiratory functions revealed that the activities of Complex I+III, Complex II+III and Complex IV all decreased drastically at 6 hr after hepatectomy and then gradually returned to the original level during 18-24 hr after hepatectomy. Interestingly, the activities of all these enzyme complexes continuously increased and were elevated significantly above the normal levels (145-200%). In contrast, the liver mitochondrial electron transport activities of sham-operated rats returned only to the original level after recovering from the operation-induced decline at 6 hr post-hepatectomy. We measured the superoxide dismutase (SOD) activity of liver mitochondria of the hepatectomized and sham-operated rats. The results showed that the Mn-SOD activity started to increase after hepatectomy, reached a maximum (900% of control) at 6 hr, and then returned to normal levels at 24 hr after operation. The Cu, Zn-SOD activity was increased 9-fold in hepatectomized rats and about 3-fold in sham-operated rats as compared with control rats. The maximum activity of Mn-SOD was found to be about 4 times higher than that of Cu, Zn-SOD after hepatectomy. The amount of lipoperoxides in the liver mitochondria was found to be increased to 140% in hepatectomized rats and to 120% in sham-operated rats as compared with that of the control rats. Taken together these results suggest that the changes in mitochondrial respiratory functions in the early phase of hepatectomy are due to tissue damage caused by the transient elevation of free radicals. These free radicals are then quickly disposed of by the ever-increasing activities of the Mn-SOD and Cu, Zn-SOD in the liver mitochondria, thereby protecting the liver from further damage and gearing the organ to the regeneration process.
本研究的总体目标是检测大鼠线粒体呼吸功能与肝再生之间的关系。同时评估了自由基在该过程中可能发挥的作用。结果发现，肝切除术后6小时呼吸控制率和ADP/O比值同时降至最低水平，此后逐渐恢复。这两个比值在48小时时显著升高，并迅速达到平台期水平。线粒体呼吸功能检测显示，肝切除术后6小时，复合体I+III、复合体II+III和复合体IV的活性均急剧下降，然后在肝切除术后18-24小时逐渐恢复到原始水平。有趣的是，所有这些酶复合体的活性持续增加，并显著高于正常水平（145%-200%）。相比之下，假手术大鼠的肝线粒体电子传递活性在肝切除术后6小时从手术引起的下降中恢复后仅恢复到原始水平。我们测量了肝切除大鼠和假手术大鼠肝线粒体的超氧化物歧化酶（SOD）活性。结果显示，肝切除术后Mn-SOD活性开始增加，在6小时时达到最大值（对照的900%），然后在术后24小时恢复到正常水平。与对照大鼠相比，肝切除大鼠的Cu,Zn-SOD活性增加了9倍，假手术大鼠增加了约3倍。肝切除术后发现Mn-SOD的最大活性约为Cu,Zn-SOD的4倍。与对照大鼠相比，肝切除大鼠肝线粒体中的脂质过氧化物含量增加到140%，假手术大鼠增加到120%。综合这些结果表明，肝切除早期线粒体呼吸功能的变化是由于自由基短暂升高引起的组织损伤。然后，这些自由基被肝线粒体中不断增加的Mn-SOD和Cu,Zn-SOD活性迅速清除，从而保护肝脏免受进一步损伤，并使器官适应再生过程。
