秦皮甲素减轻脂多糖刺激小鼠急性肾损伤和炎症反应的作用及其机制

Esculin alleviates acute kidney injury and inflammation induced by LPS in mice and its possible mechanism

急性肾损伤是临床常见的严重疾病。秦皮甲素是一种香豆素类化合物,前期研究发现秦皮甲素对糖尿病大鼠肾脏损伤具有保护作用,本研究旨在探讨秦皮甲素对脂多糖(LPS)致小鼠急性肾损伤的作用及其可能机制。H&E染色观察肾脏形态;测定血尿素氮(BUN)水平和血清肌酐含量评价肾功能;ELISA法检测炎症因子水平;RT-PCR和Western blotting分析炎症蛋白表达水平。结果表明,ES可减轻LPS所致的病理损伤和肾功能损伤,降低血清BUN水平和肌酐含量;此外,ES显著降低肾组织中IL-1β、IL-6和TNF-α、趋化因子MCP-1和细胞黏附分子ICAM-1等的释放。进一步研究发现,秦皮甲素在m RNA水平和蛋白水平下调LPS导致的小鼠肾组织中炎症通路蛋白P2X7、HMGB1、TLR4和MyD88的表达。以上结果表明,秦皮甲素对LPS刺激所致急性肾损伤具有保护作用,抑制炎症反应与下调P2X7和HMGB1/TLR4炎症通路相关。

Acute kidney injury(AKI)is a common clinical serious illness.Esculin(ES)is a coumarin compound of traditional Chinese medicine Cortex Fraxini.Our previous study has found that ES protects against inflammation and renal damage in diabetic rats.In the present study,we aimed to investigate the effects and the possible mechanism of ES against lipopolysaccharides(LPS)-induced AKI in mice.Renal morphology was observed by H&E staining.Renal function was evaluated by blood urea nitrogen(BUN)level and creatinine content in serum.Inflammatory factor levels were measured by ELISA assay.The inflammatory proteins were analyzed by RT-PCR and Western blotting analysis.The results showed that ES alleviated LPS-induced pathological injury and renal dysfunction,and decreased BUN level and creatinine content in serum.In addition,ES significantly reduced the release of pro-inflammatory factors,including IL-1β,IL-6 and TNF-α,chemokine MCP-1 and cell adhesion molecule ICAM-1.Furthermore,the expressions of inflammatory pathway proteins P2 X7,HMGB1,TLR4 and MyD88 both at the mRNA and protein levels were all down-regulated by ES in the kidney tissue of LPS-challenged mice.These results suggested ES protected against LPS-induced AKI through inhibiting P2 X7 expression and HMGB1/TLR4 inflammatory pathway.