The transcriptional change of mitochondrial genome in mice models for acetaminophen-induced acute liver injury and failure
MING Ya-nan, LI Chun-min, ZHANG Jing-yi, LIU Xiao-lin, MAO Yi-Min
2016, 21(6):
447-451.
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Objective To explore the relationship between transcription level of mitochondrial DNA (mtDNA) and disease progression in the mice models of acetaminophen (APAP)- induced acute liver injury (AILI) and acute liver failure (ALF), and to find the relative new biomarkers for outcome.Methods Ninety mice were randomly divided into three groups, including control group, AILI group (300 mg/kg) and ALF group (750 mg/kg). After fasting 16 h, all mice were intraperitoneally injected with same volume of saline or different doses of APAP. At different time points of 0, 1, 3, 6 and 12 h, 6 mice randomly selected from each group were sacrificed for blood and liver, respectively. Plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST) and reactive oxygen (ROS) levels were detected, and liver total RNA was extracted for RT-PCR to detect changes in transcription of mitochondrial genome. Results Compared with the control group, ALT and AST levels in AILI and ALF group were significantly increased. In AILI group, ALT peaked at 6-12 h (5000-10000 IU/L), and ALT exceeded 10000 IU/L at 12 h in ALF group, which showed significantly difference (P<0.05). Microbubbles steatosis in three zones was observed in both AILI and ALF groups, and massive hepatic necrosis (MHN) were found merely in ALF group. In 1 h after APAP injection, ROS in ALF group was about 2.5 times as much as that in AILI group, which significantly increased at all time points in both group. Contrasting with control and ALIF groups, COX1 transcriptional level in AILI group increased significantly at 6 h. In AILI and ALF group, CYTB, COX2 and ATP8 reduced significantly at 3 h (P<0.05), COX1,ND1,ND5 and ATP8 significantly decreased at 6 h (P<0.05), and transcription level of other subunits of NADH significantly decreased at 12 h (P<0.05) comparing with those in control group. Furthermore, ATP6 at 6h in ALF group was obviously lower than that in AILI and control group (P<0.05). At 12 h, the majority of mtDNA (CYTB, COX2, ATP8, ND2, ND3, ND5 and ND6 ) had significant differences between AILI and ALF group.Conclusion There are significant difference in mtDNA transcription between AILI and ALF groups. Besides COX1, other mtDNA showed significant decreases in AILI and ALF group compared with those in control group, especially in ALF group. mtDNA transcriptional changes may have great potential as biological makers to predict outcomes of AILI.
