昆明医科大学学报2024，Vol.45Issue(7)：14-22,9.DOI:10.12259/j.issn.2095-610X.S20240703
罗格列酮通过诱导HO-1减轻大鼠肝缺血再灌注损伤的作用机制
Mechanism of Rosiglitazone in Reducing Liver Ischemia Reperfusion Injury in Rats by Inducing HO-1
摘要
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 Co-mpared 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.关键词
肝缺血再灌注损伤/PPAR-γ/HO-1/肝窦内皮细胞Key words
Hepatic ischemia reperfusion injury/PPAR-γ/HO-1/Liver sinusoidal endothelial cell分类
医药卫生引用本文复制引用
杨轶涵,陈华梅,方育,王玉鑫,展希..罗格列酮通过诱导HO-1减轻大鼠肝缺血再灌注损伤的作用机制[J].昆明医科大学学报,2024,45(7):14-22,9.基金项目
云南省科技厅-昆明医科大学应用基础研究联合专项基金资助项目(202001AY070001-041) （202001AY070001-041）
