MK2基因在血管紧张素Ⅱ诱导小鼠肾损害中的作用  

Roles of MK2 gene in angiotensinⅡ-induced mouse renal damage

作　　者：孙丽爽 于洋 冯艳红 SUN Lishuang;YU Yang;FENG Yanhong(Department of Ultrasonography,Third Affiliated Hospital of Jinzhou Medical University,Jinzhou 121000,China;Department of Ultrasonography,First Affiliated Hospital of Jinzhou Medical University,Jinzhou 121011,China)

机构地区：[1]锦州医科大学附属第三医院超声科,121000 [2]锦州医科大学附属第一医院超声科,121011

出　　处：《免疫学杂志》2024年第5期446-451,共6页Immunological Journal

基　　金：辽宁省自然科学基金(20180530009)。

摘　　要：目的研究丝裂原活化蛋白激酶激活的蛋白激酶2(MK2)在血管紧张素Ⅱ(AngⅡ)诱导小鼠肾损害中的作用机制。方法6只野生型C57BL/6J小鼠随机分为MK2^(+/+)对照组、MK2^(+/+)+AngII组,16只MK2敲除C57BL/6J小鼠随机分为MK2^(-/-)对照组、MK2^(-/-)+AngII组,采用皮下注射AngⅡ的方式诱导肾损害、持续4周。检测收缩压、血肌酐、24 h尿白蛋白、肾小球硬化指数、肾小管间质损伤分数、肾脏中磷酸化MK2(p-MK2)、p-p65核因子-κB(NF-κB)的表达水平及肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、活性氧簇(ROS)、超氧化物歧化酶(SOD)、丙二醛(MDA)的含量。结果与MK2^(+/+)对照组比较,MK2^(+/+)+AngⅡ组的收缩压、血肌酐、24h尿白蛋白、肾小球硬化指数、肾小管间质损伤分数、肾脏中p-MK2、p-p65 NF-κB的表达水平及TNF-α、IL-6、ROS、MDA的含量增加,肾脏中SOD的含量降低(P<0.05);与MK2^(+/+)+AngII组比较,MK2^(-/-)+AngⅡ组的收缩压无显著差异(P>0.05),血肌酐、24h尿白蛋白、肾小球硬化指数、肾小管间质损伤分数、肾脏中p-MK2、p-p65 NF-κB的表达水平及TNF-α、IL-6、ROS、MDA的含量降低,肾脏中SOD的含量增加(P<0.05)。结论敲除MK2后显著减轻AngⅡ诱导肾损害并抑制炎症反应、氧化应激反应,MK2参与AngⅡ诱导肾损害的发生。This study was designed to evaluate the effect and mechanism of mitogen-activated protein kinase(MAPK)activated protein kinase 2(MK2)in AngiotensinⅡ(AngⅡ)-induced mouse renal damage.Total of 16 wild type C57BL/6J mice were randomly divided into MK2^(+/+)control group and MK2^(+/+)+AngⅡgroup,while 16 MK2 knockout C57BL/6J mice were randomly divided into MK2^(-/-)control group and MK2^(-/-)+AngII group.Kidney damage was induced by subcutaneous injection of AngⅡfor 4 weeks.Then corresponding methods were carried out to detect systolic pressure,serum creatinine,24h urinary albumin,glomerulosclerosis index,renal tubulointerstitial injury score,the expression level of phosphorylated MK2(p-MK2),p-p65 nuclear factor-κB(NF-κB),the contents of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),reactive oxygen species(ROS),superoxide dismutase(SOD)and malondialdehyde(MDA).Compared with the MK2^(+/+)control group,MK2^(+/+)+AngII group demonstrated significant increase in systolic blood pressure,serum creatinine,24h urinary albumin,glomerulosclerosis index,renal tubulointerstitial injury score,the expression levels of p-MK2,p-p65 NF-κB expression,and the contents of TNF-α,IL-6,ROS,MDA,while significant decrease in the level of SOD in kidney(P<0.05).Compared with the MK2^(+/+)+AngII group,MK2^(-/-)+AngⅡgroup showed no significant difference in systolic blood pressure(P>0.05),significant decrease in the serum creatinine,24 h urinary albumin,glomerulosclerosis index,renal tubulointerstitial injury score,the expression levels of p-MK2,p-p65 NF-κB and the contents of TNF-α,IL-6,ROS,MDA,while significant increase in the content of SOD in kidney(P<0.05).In conclusion,MK2 knockout significantly alleviates AngⅡ-induced renal damage and inhibits inflammatory and oxidative stress responses.MK2 is involved in AngⅡinduced renal damage.

关 键 词：高血压肾病 血管紧张素Ⅱ 丝裂原活化蛋白激酶激活的蛋白激酶2 基因敲除 

分 类 号：R544.1[医药卫生—心血管疾病]