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| Regulation of Endoplasmic Reticulum Stress by Adenosine A2a Receptor Agonists in Septic Acute Kidney Injury |
| WANG Jingjing, BAYINCHAHAN Boranyi, GUO Junchuan |
| The People's Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Urumqi 830000, China |
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Abstract Objective: To investigate the effects of adenosine A2a receptor agonist on ER stress (ERS) pathway and monocyte chemotactic protein 1 (MCP-1) expression in sepsis acute kidney injury (AKI) model rats. Methods: The experiment was divided into 4 groups,including control group,adenosine A2a receptor agonist (CGS21680) group,model group (AKI) group,and adenosine A2a receptor agonist intervention group (CGS21680+AKI) group,with 10 SD rats in each group.CGS21680 group and CGS21680+AKI group were intrapitoneal injected with CGS21680,then the other three groups of rats except the control group were prepared with AKI model.One week later,serum creatinine (SCr) and urea nitrogen (BUN) levels were detected by automatic biochemical analyzer,and serum renal injury molecule-1 (KIM-1) and neutrophil-gelatinase-associated lipid carrier protein (NGAL) levels were detected by enzyme-linked immunosorbent assay (ELISA),Hematoxylin-eosin (HE) staining and PAS staining were used to observe the pathological changes of renal tissue,TDT-mediated dUTP Notch end labeling (TUNEL) staining was used to observe the apoptosis of cells in renal tissue.Immunohistochemical staining was used to detect CCAAT/enhancer binding protein homologous protein (CHOP) and glucose regulatory protein 78 (GRP78) in renal tissue,Western blot was used to determine the protein expression level of X-box-bound protein-1 (XBP1),protein kinase R-like endoplasmic reticulum kinase (PERK),eukaryotic initiation transcription factor 2α subunit (eIF2α) and phosphorylated eukaryotic initiation factor 2α (p-eIF2α) in renal tissue,immunohistochemical staining was used to detect the positive expression of MCP-1 in renal tissue,and Western blot was used to determine the protein expression level of MCP-1 in renal tissue. Results: Compared with the control group,the levels of SCr,BUN,KIM-1 and NGAL in AKI group were increased (P<0.05),the renal tubule dilatation,degeneration and glomerular edema were observed in renal tissue,the positive rate of TUNEL was increased (P<0.05),the positive expressions of GRP78 and CHOP were increased (P<0.05),the relative protein expression levels of XBP1 and PERK and the ratio of eIF2α/P-EIF2α in renal tissue were up-regulated (P<0.05),and the proportion of MCP-1 positive expression and the relative expression level of protein were also increased and up-regulated (P<0.05).Compared with AKI group,the levels of SCr,BUN,KIM-1 and NGAL in CGS21680+AKI group were decreased (P<0.05),the pathological damage of renal tissue was significantly improved,the positive rate of TUNEL was decreased (P<0.05),and the positive expressions of GRP78 and CHOP were decreased (P<0.05).The relative protein expression levels of XBP1 and PERK and the ratio of eIF2α/P-EIF2α in renal tissues were down-regulated (P<0.05), meanwhile,the positive expression ratio of MCP-1 and the relative expression level of MCP-1 were also down-regulated (P<0.05). Conclusion: Adenosine A2a receptor agonist can alleviate acute kidney injury in AKI rats,which may be related to its alleviation of endoplasmic reticulum stress and inhibition of MCP-1 level.
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2023, Vol. 29 
