RESUMO
The aim of this study was to investigate the protective effect of Polygonatum sibiricum polysaccharides (PSP) on acute kidney injury (AKI) in rats. The AKI model was established with 100 mg/kg of gentamicin (GM) intramuscularly. Six hours post-injection, rats were given intragastrically different dosages of PSP (0.25, 0.5, and 1 g/kg) for seven consecutive days. Results showed that compared with the model group, the kidney coefficient of rats decreased significantly (P < 0.05), and rat serum CRE and urea levels were significantly decreased (P < 0.05) in the PSP treatment group. The expression of NGAL, KIM-1, IL-1ß, IL-6, TNF-α, and p38 MAPK mRNA in the kidney were significantly decreased (P < 0.05). The protein expression of p38 MAPK, p-p38 MAPK, and p-ATF2 were decreased to different degrees. Among the three-PSP treatment groups, the medium-dose group displayed the most protective effects. In conclusion, PSP had a powerful protective effect on GM-induced AKI in rats, it decreased the expression of NGAL or KIM-1 mRNA in kidney tissue and inhibited the p38 MAPK/ATF2 signaling pathway and the production of inflammatory factors TNF-α, IL-1ß, and IL-6.
Assuntos
Fator 2 Ativador da Transcrição/metabolismo , Injúria Renal Aguda/metabolismo , Polygonatum/química , Polissacarídeos/farmacologia , Substâncias Protetoras/farmacologia , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/patologia , Animais , Biomarcadores , Biópsia , Análise Química do Sangue , Modelos Animais de Doenças , Expressão Gênica , Gentamicinas/efeitos adversos , Testes de Função Renal , Masculino , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Substâncias Protetoras/química , Substâncias Protetoras/isolamento & purificação , RatosRESUMO
AIM:To investigate the role of p38 MAPK/ATF-2 pathway in C-relative protein ( CRP)-induced endothelial cell activation.METHODS:Human coronary artery endothelial cells ( HCAEC) were cultured and were used between passages 3 and 7.CRP served as a stimulus for endothelial cell activation.Western blotting was performed to de-termine the expression and phosphorylation of eNOS, p38 and ATF2.ELISA was carried out to detect the levels of ICAM-1, VCAM-1 and MCP-1 released from HCAEC.Pharmacological p38 inhibitors SB203580 and SB202190 were used to de-termine the effect of p38/ATF-2 pathway.RESULTS:CRP reduced the p-eNOS level in a concentration-dependent man-ner and induced the release of ICAM-1, VCAM-1 and MCP-1.The p38/ATF-2 pathway was activated by CRP treatment. SB203580 and SB202190 partially rescued p-eNOS level and suppressed the secretion of ICAM-1, VCAM-1 and MCP-1. CONCLUSION:p38MAPK/ATF-2 pathway participates in CRP-induced endothelial activation.