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

作　　者：叶少军[1] 钟自彪[1] 刘忠忠 胡前超 范晓礼[1] 靖凯[1] 周敏[1] 熊艳[1] 王彦峰[1] 叶啟发[2] 

机构地区：[1]武汉大学中南医院武汉大学肝胆疾病研究院武汉大学移植医学中心移植医学技术湖北省重点实验室,430071 [2]中南大学湘雅三医院卫生部移植医学工程技术研究中心,长沙410013

出　　处：《中华器官移植杂志》2017年第9期564-568,共5页Chinese Journal of Organ Transplantation

基　　金：国家自然科学基金新疆联合项目（U1403222）

摘　　要：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.

关 键 词：甘草皂苷 缺血 再灌注损伤 肾功能 机制 

分 类 号：R692[医药卫生—泌尿科学]