高良姜素防治尿酸性肾损伤的药理作用及细胞机制研究  

Pharmacological effect and cellular mechanism of galangin on uric acid nephropathy

作　　者：卢昊 陈曦文 要辉 许汉林 LU Hao;CHEN Xi-wen;YAO Hui;XU Han-lin(School of Pharmacy,Hubei University of Traditional Chinese Medicine,Wuhan 430065)

机构地区：[1]湖北中医药大学药学院,武汉430065

出　　处：《中南药学》2020年第7期1098-1102,共5页Central South Pharmacy

基　　金：湖北省科学技术厅高校产学研合作项目(No.2019AFB871)。

摘　　要：目的探讨高良姜素防治尿酸性肾损伤(UAN)的药理作用及细胞机制。方法将60只小鼠随机均分为对照组、模型组、别嘌醇组(40 mg·kg^(-1))及高良姜素低、中、高剂量组(100、200、400 mg·kg^(-1)),除对照组外,其余各组均上午腹腔注射氧嗪酸钾和灌胃酵母浸膏建立小鼠UAN模型,下午给予相应药物灌胃治疗,每日1次,持续15 d。实验结束后,全自动生化分析仪检测高良姜素对小鼠血清中尿酸(UA)、肌酐(Cr)及尿素氮(BUN)水平的影响,黄嘌呤氧化酶(XOD)试剂盒检测高良姜素对小鼠肝脏中XOD活力的影响。UA诱导NRK-52E细胞制备炎症模型,CCK8法检测高良姜素对NRK-52E细胞活力影响,酶联免疫吸附法(ELISA)检测高良姜素对细胞上清中白细胞介素-1β(IL-1β)和白细胞介素-18(IL-18)水平的影响,Western-blot法检测高良姜素对细胞核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)炎性小体蛋白表达的影响。结果高良姜素能显著降低UAN模型小鼠血清UA、Cr、BUN水平和肝脏XOD活力(P<0.05或P<0.01),并抑制UA诱导的NRK-52E细胞炎症因子IL-1β、IL-18的释放和NLRP3、ASC、Caspase-1的表达(P<0.05或P<0.01)。结论高良姜素具有明显防治UAN的药理作用,其机制可能与高良姜素降低XOD活力、抑制NLRP3炎性小体激活有关。Objective To determine the pharmacological effect and cell mechanism of galangin in the prevention and treatment of uric acid nephropathy(UAN).Methods Totally 60 mice were randomly divided into a control group,a model group,an allopurinol group(40 mg·kg-1),and 3 galangin(low,medium and high dose)groups(100,200,400 mg·kg-1).Except for the control group,the other groups were intraperitoneally injected with potassium oxyzinate and gavage yeast extract in the morning to establish the mouse model of UAN,and corresponding drugs were administered by gavage in the afternoon,once daily for 15 days.After the experiment,the effects of galangin on the levels of uric acid(UA),creatinine(Cr),and urea nitrogen(BUN)in the serum were detected by automatic biochemical analyzer.The activity of xanthine oxidase(XOD)in the liver was detected by XOD kit.NRK-52E cells were induced by UA to establish the inflammatory cell model.The effect of galangin on the activity of NRK-52E cells was detected by CCK8 method,and the IL-1βand IL-18 in the supernatant of NRK-52E cells were detected by enzyme-linked immunosorbent assay.Western blot was used to detect the effect of galangin on the expression of nucleoside binding domain like receptor protein 3(NLRP3)inflammasome.Results Galangin significantly reduced the levels of UA,Cr,BUN in the serum and XOD activity in the liver of UAN mice(P<0.05 or P<0.01),and also inhibited the release of IL-1β,IL-18 and the expression of NLRP3,ASC and caspase-1 in NRK-52E cells induced by UA(P<0.05 or P<0.01).Conclusion Galangin has an obvious pharmacological effect on the prevention and treatment of UAN,whose mechanism may be related to the reduction of XOD activity and the inhibition of NLRP3 inflammasome activation.

关 键 词：高良姜素 尿酸性肾损伤 抗炎 细胞机制 

分 类 号：R286[医药卫生—中药学]