甘草素减轻小鼠肾脏缺血再灌注损伤的作用及其机制研究

Research on the protective effect of glycyrrhizin against renal ischemia-reperfusion injury in mice and its mechanisms

目的探讨甘草素对小鼠肾脏缺血再灌注损伤的作用及其作用机制。方法C57BL/6雄性小鼠，随机分为假手术组、生理盐水组和甘草素组，每组6只。采用双侧切口摘除右肾，夹闭左肾动脉30 min后恢复血液灌注，建立缺血再灌注损伤模型。假手术组，仅行双侧腹部切口摘除右肾；甘草素组，术前1 h注射甘草素，60 mg/kg；生理盐水组注射等量的生理盐水。恢复灌注6 h时将小鼠处死，收集其血液和肾脏样本，用于肾脏功能、炎症反应及信号通路等相关指标的检测。结果缺血再灌注6 h时，与生理盐水组比较，甘草素组小鼠血肌酐和尿素氮水平显著下降（P〈0.01），超氧化物阴离子含量降低（P〈0.01），超氧化物歧化酶活性增加（P〈0.01）。甘草素组髓过氧化物酶活性（P〈0.01）和促炎症细胞因子肿瘤坏死因子α（P〈0.05）、γ干扰素（P〈0.05）、白细胞介素1β（P〈0.01）和白细胞介素6（P〈0.01）的表达明显减少，且Phospho-P38 MAPK蛋白水平显著下调（P〈0.05）。结论甘草素预处理能抑制P38 MAPK信号通路的激活，减轻肾脏缺血再灌注炎症反应，从而能减轻小鼠肾脏缺血再灌注损伤。

ObjectiveTo investigate the protective effect of glycyrrhizin against renal ischemia-reperfusion injury in mice and its mechanisms.MethodsMale C57BL/6 mice were divided into three groups of six. Bilateral flank incisions were made, the right kidney was removed and the left kidney was subjected to ischemia using a microvascular clamp, which was removed after 30 min. In the sham-operated group, the mice underwent anesthesia, bilateral flank incisions and a right nephrectomy. In the glycyrrhizin-treated group, the mice were injected with 60 mg/ kg glycyrrhizin 1 h prior to ischemia. In the saline-treated group, the mice were administered with 60 mg/ kg saline. The mice were sacrificed 6 h after reperfusion and the blood and kidney samples were immediately collected for kidney function, inflammatory response and signal pathway test.ResultsAs compared with those in the saline-treated group, the mice in glycyrrhizin0-treated group exhibited notably decreased serum levels of creatine and blood urea nitrogen at 6 h following reperfusion （P〈0.01）, the SOA level was significantly reduced （P〈0.01） and the SOD activity was increased. The activity of MPO （P〈0.01） in the glycyrrhizin-treated group was significantly reduced as compared with the saline-treated group, also the serum level of pro-inflammatory TNF-α （P〈0.05）, IFN-γ （P〈0.05）, IL-1β （P〈0.01） and IL-6 （P〈0.01）. Furthermore, the phosphorylated-p38 protein level in the glycyrrhizin-treated group was notably as reduced compared with that in the saline-treated group.ConclusionPretreatment with glycyrrhizin attenuates renal ischemia-reperfusion injury via inhibition of tissue inflammation by downregulating p38 mitogen-activated protein kinase signaling.