甘草素对急性肾损伤小鼠的保护机制研究

Protective mechanism of liquiritigenin on acute kidney injury in mice

目的探究甘草素对脂多糖(LPS)诱导的急性肾损伤小鼠的保护作用机制。方法将雄性昆明小鼠随机分为对照组、LPS组、LPS+甘草素3.75 mg/kg组、LPS+甘草素7.5 mg/kg组、LPS+甘草素15 mg/kg组和LPS+地塞米松组,每组8只。苏木素-伊红(HE)染色观察肾组织病理变化;全自动生化分析仪检测血清肌酐和血清尿素氮水平。酶联免疫吸附测定(ELISA)检测肾组织中IL-6、IL-1β和TNF-α水平;Western blot检测肾组织中IκBα和NF-κBp65蛋白的磷酸化水平和Toll样受体4(TLR4)、NOD样受体热蛋白结构域相关蛋白3(NLRP3)、Caspase-1、IL-1β蛋白表达水平。结果与对照组相比,LPS组小鼠肾组织中有大量炎症细胞浸润,血清肌酐、血清尿素氮、IL-6、IL-1β、TNF-α水平及p-IκBα/IκBα、p-NF-κBp65/NF-κBp65、TLR4、NLRP3、Caspase-1、IL-1β均显著上调,差异均有统计学意义(P<0.05)。然而在LPS+甘草素7.5 mg/kg组、LPS+甘草素15 mg/kg组和LPS+地塞米松组中,这些指标变化均发生逆转。结论甘草素可能通过抑制NLRP3和NF-κB信号通路缓解LPS诱导的小鼠急性肾损伤。

Objective To explore the protective mechanism of liquiritigenin on lipopolysaccharide(LPS)-induced acute kidney injury in mice.Methods Male Kunming mice were randomly divided into the control group,the LPS group,the LPS+liquiritigenin 3.75 mg/kg group,the LPS+liquiritigenin 7.5 mg/kg group,the LPS+liquiritigenin 15 mg/kg group and the LPS+dexamethasone group,with 8 mice in each group.The pathologic changes of kidney tissue were observed by hematoxylin-eosin(HE)staining.The levels of serum creatinine and serum urea nitrogen were detected by automatic biochemical analyzer.The levels of IL-6,IL-1βand TNF-αin renal tissue were detected by enzyme-linked immunosorbent assay(ELISA).Western blot was used to detect the phosphorylation levels of IκBαand NF-κBp65 protein and the expression levels of Toll-like receptor 4(TLR4),NOD-like receptor thermal protein domain associated protein 3(NLRP3),Caspase-1 and IL-1βproteins in renal tissue.Results Compared with the control group,there were a large number of inflammatory cell infiltration in the renal tissue of mice in the LPS group,and the levels of serum creatinine,serum urea nitrogen,IL-6,IL-1βand TNF-αand p-IκBα/IκBα,p-NF-κBp65/NF-κBp65,TLR4,NLRP3,Caspase-1 and IL-1βwere significantly up-regulated,the differences were statistically significant(P<0.05).However,the changes of these indexes were reversed in the LPS+liquiritigenin 7.5 mg/kg group,the LPS+liquiritigenin 15 mg/kg group and the LPS+dexamethasone group.Conclusion Liquiritigenin may alleviate LPS-induced acute kidney injury in mice by inhibiting NLRP3 and NF-κB signaling pathways.