非布司他对高尿酸血症模型大鼠血清尿酸水平和肾组织中NLRP3蛋白表达水平的影响  

Effects of febuxostat on serum uric acid level and expression level of NLRP3 protein in kidney tissue in hyperuricemia model rats

作　　者：尤杨[1] 夏岳[1] 戚国庆[1] 高宏阳[2] 杨志瑜[1] 李柳[1] 赵红亮[1] YOU Yang;XIA Yue;QI Guoqing;GAO Hongyang;YANG Zhiyu;LI Liu;ZHAO Hongliang(Department of Cardiology,First Hospital,Hebei Medical University,Shijiazhuang 050031,China;Department of Orthopaedics,First Hospital,Hebei Medical University,Shijiazhuang 050031,China)

机构地区：[1]河北医科大学第一医院心内三科,河北石家庄050031 [2]河北医科大学第一医院骨二科,河北石家庄050031

出　　处：《吉林大学学报（医学版）》2019年第6期1367-1372,I0020,共7页Journal of Jilin University：Medicine Edition

基　　金：河北省科技厅重点研发计划项目资助课题(18277742D)

摘　　要：目的:探讨非布司他对高尿酸血症模型大鼠血清尿酸水平和肾组织中核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)蛋白表达水平的影响,并阐明其作用机制。方法:将45只大鼠随机分为对照组、高尿酸血症组和非布司他组,每组15只。高尿酸血症组和非布司他组大鼠采用氧嗪酸钾灌胃建立高尿酸血症模型,非布司他组大鼠每天给予7.2 mg·kg-1非布司他,对照组大鼠每天给予等量生理盐水,共4周。HE染色观察各组大鼠肾组织病理形态表现。全自动生化仪测定各组大鼠血清尿酸、肌酐和尿素氮水平,酶联免疫吸附测定(ELISA)法测定各组大鼠血清白细胞介素1β(IL-1β)和白细胞介素18(IL-18)水平,免疫组织化学法测定各组大鼠肾组织中凋亡相关斑点样蛋白(ASC)和NLRP3蛋白表达水平。结果:与对照组比较,高尿酸血症组大鼠尿量和饮水量升高(t=5.317,t=3.674,P<0.05),体质量降低(t=6.374,P<0.05),血清尿酸、肌酐和尿素氮水平升高(t=21.463,t=15.342,t=4.603,P<0.05),血清IL-1β和IL-18水平升高(t=35.761,t=44.168,P<0.05),肾组织中ASC和NLRP3蛋白表达水平升高(t=17.064,t=26.314,P<0.05);与高尿酸血症组比较,非布司他组大鼠尿量和饮水量降低(t=4.027,t=2.976,P<0.05),体质量升高(t=3.694,P<0.05),血清尿酸、肌酐和尿素氮水平降低(t=13.064,t=7.461,t=3.528,P<0.05),血清IL-1β和IL-18水平降低(t=24.162,t=17.314,P<0.05),肾组织中ASC和NLRP3蛋白表达水平降低(t=8.061,t=11.057,P<0.05)。结论:非布司他可能通过抑制大鼠肾组织中NLRP3炎症小体的激活及其下游炎性因子水平发挥对高尿酸血症模型大鼠的肾脏保护作用。Objective:To discuss the effects of febuxostat on the serum uric acid level and the expression level of nucleotide-binding oligomerization domain-like receptorProtein 3(NLRP3)Protein in the hyperuricemia model rats,and to elucidate their mechanisms.Methods:A total of 45 rats were randomly divided into control group,hyperuricemia group and febuxostat group,and there were 15 rats in each group.The rat models of hyperuricemia were established in hyperuricemia group and febuxostat group by intragastric administration ofPotassium oxonate.The rats in febuxostat group were given a daily dose of 7.2 mg·kg-1 febuxostat,and the rats in control group were administrated with the same volume of normal saline,lasted for 4 weeks.HE staining was used to observe thePathomorphology of kidney tissue of the rats in various groups,automatic biochemical analyzer was used to detect the levels of serum uric acid,creatinine and urea nitrogen of the rats in various groups,ELISA method was used to determine the levels of serum interleukin-1β(IL-1β)and interleukin-18(IL-18)of the rats in various groups,and immunohistochemistry method wasPerformed to detect the expression levels of apoptosis-associated speck-likeProtein(ASC)and NLRP3Proteins in kidney tissue of the rats in various groups.Results:Compared with control group,the urine volume and water intake of the rats in hyperuricemia group were increased(t=5.317,t=3.674,P<0.05),the body weight was decreased(t=6.374,P<0.05),the levels of serum uric acid,creatinine and urea nitrogen were increased(t=21.463,t=15.342,t=4.603,P<0.05),the serum IL-1βand IL-18 levels were increased(t=35.761,t=44.168,P<0.05),and the expression levels of ASC and NLRP3Protein in kidney tissue were increased(t=17.064,t=26.314,P<0.05);compared with hyperuricemia group,the urine volume and water intake of the rats in febuxostat group were decreased(t=4.027,t=2.976,P<0.05),the body weight was increased(t=3.694,P<0.05),the serum blood uric acid,creatinine and urea nitrogen levels were decreased(t=13.064,t=7.461,t=3.52

关 键 词：非布司他 高尿酸血症 核苷酸结合寡聚化结构域样受体蛋白3 白细胞介素1Β 白细胞介素18 

分 类 号：R696.6[医药卫生—泌尿科学]