Mechanism of Rosiglitazone in Reducing Liver Ischemia Reperfusion Injury in Rats by Inducing HO-1

Yihan YANG; Huamei CHEN; Yu FANG; Yuxin WANG; Xi ZHAN

doi:10.12259/j.issn.2095-610X.S20240703

Volume 45 Issue 7

Jul. 2024

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Article Navigation > Journal of Kunming Medical University > 2024 > 45(7): 14-22

Yihan YANG, Huamei CHEN, Yu FANG, Yuxin WANG, Xi ZHAN. Mechanism of Rosiglitazone in Reducing Liver Ischemia Reperfusion Injury in Rats by Inducing HO-1[J]. Journal of Kunming Medical University, 2024, 45(7): 14-22. doi: 10.12259/j.issn.2095-610X.S20240703

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Yihan YANG, Huamei CHEN, Yu FANG, Yuxin WANG, Xi ZHAN. Mechanism of Rosiglitazone in Reducing Liver Ischemia Reperfusion Injury in Rats by Inducing HO-1[J]. Journal of Kunming Medical University, 2024, 45(7): 14-22. doi: 10.12259/j.issn.2095-610X.S20240703

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Mechanism of Rosiglitazone in Reducing Liver Ischemia Reperfusion Injury in Rats by Inducing HO-1

doi: 10.12259/j.issn.2095-610X.S20240703

Dept. of Anesthesiology，The 1st Affiliated Hospital of Kunming Medical University，Kunming Yunnan 650032，China

Received Date: 2024-03-15
Available Online: 2024-06-14
Publish Date: 2024-07-25

Abstract

Abstract

Objective To observe whether rosiglitazone, a peroxisome proliferator-activated receptor （PPAR-γ） agonist, can attenuate hepatic ischemia-reperfusion injury （IRI） in rats by modulating heme oxygenase 1 （HO-1） activity. Methods A rat 70% hepatic thermal ischemia/reperfusion （I/R） model and hypoxia-glucose deprivation/reperfusion （OGD/R）-induced liver sinusoidal endothelial cells （LSECs） injury model in rats were established. The rats were randomly divided into sham operation group, model group, rosiglitazone pretreatment group and zinc protoporphyrin （ZnPP） group （n = 6/group）. The serum ALT and AST levels of rats were detected by fully automatic biochemical analyzer. HE staining was used to assess liver histopathological injury. PPAR-γ and HO-1 protein expression levels were detected by Western Blot. The cell viability of LSECs was determined by CCK8 method, and reactive oxygen species （ROS） content in LSECs was determined by flow cytometry. Results Compared with the I/R model group, rosiglitazone pretreatment significantly decreased ALT and AST levels, reduced liver cell apoptosis, and alleviated liver tissue IRI （P < 0.01）. WB results showed that rosiglitazone upregulated the expression of PPAR-γ and HO-1protein （P < 0.01）. In addition, compared with the OGD/R model group, rosiglitazone pretreatment （10, 30 μmol/L） improved the survival rate of OGD/ R-induced LSECs and significantly reduced the ROS content in cells in a dose-responsive manner （P < 0.01）. When ZnPP blocked HO-1 activity, the protective effect of rosiglitazone on hepatic IRI in rats disappeared. Conclusion Rosiglitazone can mediate antioxidant and anti-inflammatory effects through up-regulation of HO-1 activity and reduce hepatic IRI in rats.
- Hepatic ischemia reperfusion injury,
- PPAR-γ,
- HO-1,
- Liver sinusoidal endothelial cell

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References(30)

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