山柰酚对LPS诱导小鼠急性肾损伤作用及机制探讨  

Effect and Possible Mechanism of Kaempferol on Acute Kidney Injury in LPS-Stimulated Mice

作　　者：程笑 杨滢霖 李伟瀚 刘漫 王月华 杜冠华 CHENG Xiao;YANG Ying-lin;LI Wei-han;LIU Man;WANG Yue-hua;DU Guan-hua(Beijing Key Laboratory of Drug Target Identification and New Drug Screening,Institute of Materia Medica,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100050,China)

机构地区：[1]中国医学科学院北京协和医学院药物研究所,药物靶点研究与新药筛选北京市重点实验室,北京100050

出　　处：《中国药学杂志》2020年第17期1439-1443,共5页Chinese Pharmaceutical Journal

基　　金：国家重点研发计划项目资助(2018YFC0311005);国家自然科学基金面上项目资助(81473383);国家科技重大专项重大新药创制项目资助(2018ZX09711001-003-019);中国医学科学院医学与健康科技创新工程项目资助(2016-I2M-3-007);北京协和医学院研究生创新基金项目资助(2018-1007-04)。

摘　　要：目的研究山柰酚(KAE)对脂多糖(LPS)诱导小鼠急性肾损伤的作用及其机制。方法BALB/c小鼠随机分为正常对照组、LPS模型组、KAE 25、50、100 mg·kg-1药物处理组。KAE给药7 d后,LPS模型组和KAE给药组腹腔注射LPS 5 mg·kg-1,6 h后取血清和肾组织进行检测。检测血清尿素氮和肌酐含量评价肾功能;ELISA法检测肾组织中白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)和细胞间黏附分子-1(ICAM-1)水平;Western blot检测炎症通路相关蛋白的表达。结果与正常对照组比较,LPS模型组血清尿素氮和肌酐水平显著增高;与LPS模型组比较,KAE可剂量依赖性降低尿素氮和肌酐水平。与正常对照组比较,肾组织中炎症相关因子及蛋白IL-1β、IL-6、TNF-α、ICAM-1、P2X7、HMGB1、TLR4水平显著增高,而KAE可剂量依赖性降低肾组织促炎因子、黏附分子释放,并下调炎症通路蛋白的表达。结论KAE对LPS刺激引起的小鼠急性肾脏损伤和炎症反应具有保护作用,机制可能与下调炎症蛋白HMGB1、TLR4和P2X7受体相关。OBJECTIVE To investigate the effect of kaempferol(KAE)on acute kidney injury induced by lipopolysaccharide(LPS)in mice and its mechanism.METHODS BALB/c mice were randomly divided into normal control group,LPS model group,KAE 25,50,100 mg·kg-1 treatment groups.After 7 d of administration,mice in LPS model group and KAE administration groups were injected with LPS 5 mg·kg-1 intraperitoneally,and serum and kidney tissues were collected for detection after LPS injection 6 h.The levels of urea nitrogen(BUN)and creatinine(CRE)in serum were measured to evaluate renal function;the levels of IL-1β,IL-6,TNF-αand ICAM-1 in kidney tissues were detected by ELISA,and the expression of inflammatory pathway-related proteins was detected by Western blot.RESULTS Compared with the normal control group,the levels of BUN and CRE in serum of LPS model group were increased significantly,while KAE treatment decreased the levels of BUN and CRE in a dose-dependent manner.Compared with the normal control group,the levels of inflammatory related factors and proteins IL-1β,IL-6,TNF-α,ICAM-1,HMGB1,TLR4 and P2X7 in kidney tissues were significantly increased,while KAE treatment could decrease the release of proinflammatory factors and adhesion molecules in kidney tissue in a dose-dependent manner,and down-regulate the expression of inflammatory proteins including HMGB1,TLR4 and P2X7.CONCLUSION Kaempferol can improve renal function and inhibit acute inflammatory responses induced by LPS stimulation in mice,and the mechanism may be related to down-regulation of HMGB1,TLR4 and P2X7 inflammatory proteins.

关 键 词：急性肾损伤 山柰酚 脂多糖 

分 类 号：R965[医药卫生—药理学]