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.
出处
《中华器官移植杂志》
CAS
CSCD
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)
关键词
甘草皂苷
缺血
再灌注损伤
肾功能
机制
Glycyrrhizin
Ischemia
Reperfusion injury
Kidney function
Mechanisms