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ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 37 Issue 1
Jan.  2021
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Article Contents

Protective effect of tanshinone I in a mouse model of hepatic ischemia-reperfusion injury

DOI: 10.3969/j.issn.1001-5256.2021.01.021
  • Received Date: 2020-07-23
  • Accepted Date: 2020-08-24
  • Published Date: 2021-01-20
  •   Objective  To investigate the protective effect of tanshinone I (T-I) on hepatic ischemia-reperfusion injury (HIRI) in mice.  Methods  A total of 36 C57BL/6J mice were randomly divided into sham-operation group, ischemia-reperfusion (IR) group, IR+T-I (5 mg/kg) group, IR+T-I (10 mg/kg) group, IR+T-I (20 mg/kg) group, and IR+T-I (40 mg/kg) group, with 6 mice in each group. Each group was given intraperitoneal injection. The mice in the sham-operation group and the IR group were injected with an equal volume of the solvent olive oil; the mice in the IR+T-I groups were administered once a day for 7 consecutive days, a model of 70% HIRI was established at 2 hours after the last administration, and serum and liver samples were collected after 6 hours of reperfusion. Related kits were used to measure the serum level of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and the content of superoxide dismutase (SOD), malondialdehyde (MDA), caspase-3, and reduced glutathione (GSH) in liver tissue; HE staining was used to observe liver histopathology; the TUNEL method was used to measure the level of hepatocyte apoptosis; immunohistochemistry was used to measure the protein expression of caspase-3 and heme oxygenase-1 (HO-1). A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups.  Results  Compared with the IR group, the IR+T-I (20mg/kg) group had significant reductions in the serum levels of ALT (192.48±23.67 U/L vs 336.90±41.52 U/L, P < 0.01) and AST (123.19±9.16 U/L vs 206.90±18.81 U/L, P < 0.01), and thus 20 mg/kg was determined as the optimal concentration. Compared with the IR group, the IR+T-I (20 mg/kg) group had significant reductions in MDA (1.34±0.21 μmol/mg vs 3.48±0.95 μmol/mg, P < 0.05) and caspase-3 (0.69±0.97 μmol/mg vs 1.04±0.35 μmol/mg, P < 0.05) and significant increases in SOD (274.47±30.53 U/mg vs 160.29±27.37 U/mg, P < 0.05) and GSH (2.12±0.27 μmol/mg vs 1.03±0.42 μmol/mg, P < 0.05). HE staining showed that the IR group had disordered structure of hepatic lobules and focal or extensive degeneration and necrosis of hepatocytes; compared with the IR group, the IR+T-I (20 mg/kg) group had a reduction in the area of hepatocyte necrosis and a basically complete structure of the liver. Immunohistochemistry showed that compared with the IR group, the IR+T-I (20 mg/kg) group had significant reductions in the number of apoptotic hepatocytes and the protein expression of caspase-3 and a significant increase in the protein expression of HO-1.  Conclusion  T-I exerts a protective effect against HIRI in mice by inhibiting liver oxidative stress response and hepatocyte apoptosis.

     

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