NLRP3炎症体激活参与庆大霉素所致大鼠急性肾损伤

NLRP3 inflammasome activation involved in acute kidney injury induced by gentamicin in rats

目的探讨NOD样受体蛋白3(NLRP3)炎症体在庆大霉素所致急性肾损伤中的作用。方法 SD大鼠分为对照组、模型组和抑制剂组,模型组大鼠皮下注射庆大霉素400 mg·kg^(-1)·d^(-1),连续注射2 d,建立庆大霉素中毒性急性肾损伤动物模型,抑制剂组在注射庆大霉素之前30 min给予NLRP3抑制剂格列本脲500 mg/kg。相关试剂盒检测3组大鼠血清尿素氮(BUN)、肌酐(Cr)的水平,Western印迹检测NLRP3炎症体相关蛋白NLRP3、凋亡相关斑点样蛋白(ASC)、含半胱氨酸的天冬氨酸蛋白水解酶1(Caspase-1)的表达。结果模型组的大鼠血清BUN、Cr水平较对照组显著增高,NLRP3、ASC、Caspase-1蛋白表达水平也显著增强,NLRP3抑制剂能显著减弱模型组的大鼠血清BUN、Cr水平的上升以及NLRP3、ASC、Caspase-1蛋白的表达。结论庆大霉素所致大鼠急性肾损伤的机制与NLRP3炎症体的激活有关。

Objective To investigate the role of NLRP3 inflammasome in rats with acute kidney injury induced by gentamicin.Methods SD rats were divided into three groups,including the control group,the model group and the inhibitor group. The model group rats admitted hypodermic injection of gentamicin 400 mg·kg^（-1）·d^（-1）,two days of continuous injection,to establishment the model of gentamicin induced acute kidney injury. While,the inhibitor group given NLRP3 inhibitor 500 mg / kg glibenclamide 30 minutes before gentamicin injection. The levels of BUN and Cr in serum were detected by ELISA kits,and the expression of Caspase-1,ASC and NLRP3 were detected by Western blot. Results Compared with control group,the levels of BUN and Cr significantly increased in the model group,the expression of NLRP3,ASC and Caspase-1 also significantly increased. Compared with the model group,NLRP3 inhibitor significantly reduced Scr,BUN levels and the expression of NLRP3,ASC and Caspase-1. Conclusion These findings suggest that NLRP3 inflammasome plays an important role in the pathogenesis of acute kidney injury induced by gentamicin.