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Dynamic expression of hepatic thioredoxin mRNA in rats with non-alcoholic fatty liver disease
Xiao Yan Duan1, He Ping Zhao, Jian Gao Fan
1Department of Gastroenterology, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai, China.
Objective:
To investigate the expression and significance of thioredoxin messenger ribonucleic acid (mRNA) in the development of non-alcoholic fatty liver disease (NAFLD) induced by a high fat diet.
Methods:
A total of 48 male Wistar rats were divided into a normal control group and a model group, which were both divided into three subgroups (at weeks 9, 13 and 18, respectively). The levels of serum tumor necrosis factor-alpha (TNF-alpha), free fatty acid (FFA), total cholesterol (TC) and triglyeride (TG), changes in the serum and hepatic tissue superoxide dismutase (SOD), reduced glutathione hormone (GSH) and malondialdehyde (MDA) were measured. The expression of thioredoxin mRNA in rat livers were detected with reverse transcriptase polymerase chain reaction (RT-PCR). Meanwhile, the pathological changes of liver tissue were observed by hematoxylin-eosin stain.
Results:
Simple fatty liver was observed in model group at week 9. From weeks 13 to 18, liver histopathology showed steatohepatitis. Compared with corresponding normal groups, in the model groups the levels of TNF-alpha, FFA, TC, TG in serum, and MDA in serum and liver increased significantly, while the vitality of SOD and GSH content in serum and liver decreased remarkably. Meanwhile, in the model group, the expression of hepatic thioredoxin mRNA was significantly decreased at week 9 compared with the normal group (P < 0.01), then increased gradually, but were lower than the corresponding normal groups at all times (P < 0.01).
Conclusion:
The expression of thioredoxin mRNA is significantly lower in the liver of rats with NAFLD and might reach the lowest point after developing simple fatty liver. Meanwhile the downregulation of thioredoxin mRNA may cause the inflammatory injury initially in NAFLD.
Insights
Thioredoxin messenger ribonucleic acid (mRNA) expression is significantly reduced in non-alcoholic fatty liver disease (NAFLD) liver tissue. This downregulation may contribute to the initial inflammatory injury observed in NAFLD development.
Area of Science:
- Hepatology
- Molecular Biology
- Biochemistry
Background:
- Non-alcoholic fatty liver disease (NAFLD) is a growing health concern.
- Diet-induced NAFLD models are crucial for understanding disease mechanisms.
- Thioredoxin plays a role in cellular redox balance and inflammation.
Purpose of the Study:
- To investigate thioredoxin mRNA expression in diet-induced NAFLD.
- To determine the correlation between thioredoxin mRNA levels and NAFLD progression.
- To explore the role of thioredoxin in the inflammatory processes of NAFLD.
Main Methods:
- A high-fat diet was used to induce NAFLD in male Wistar rats.
- Serum and liver markers of oxidative stress and inflammation (TNF-alpha, FFA, TC, TG, SOD, GSH, MDA) were measured.
- Thioredoxin mRNA expression was quantified using RT-PCR, and liver pathology was assessed via H&E staining.
Main Results:
- Rats fed a high-fat diet developed simple fatty liver by week 9, progressing to steatohepatitis by weeks 13-18.
- NAFLD induced significant increases in serum and liver inflammatory markers (TNF-alpha, MDA) and lipids (FFA, TC, TG).
- Hepatic thioredoxin mRNA expression was significantly decreased at week 9 and remained lower than controls throughout the study, suggesting a role in early NAFLD pathogenesis.
Conclusions:
- Thioredoxin mRNA expression is significantly downregulated in the liver during NAFLD development.
- The lowest thioredoxin mRNA levels may coincide with the onset of simple fatty liver.
- Downregulation of thioredoxin mRNA is implicated as a potential cause of initial inflammatory injury in NAFLD.
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