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

Abstract: Objective: To discuss the effects of febuxostat on the serum uric acid level and the expression level of nucleotide-binding oligomerization domain-like receptor protein 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 of potassium 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 the pathomorphology 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 was performed to detect the expression levels of apoptosis-associated speck-like protein (ASC) and NLRP3 proteins 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-1β and IL-18 levels were increased (t=35.761,t=44.168,P<0.05),and the expression levels of ASC and NLRP3 protein 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=3.528,P<0.05),the serum IL-1β and IL-18 levels were decreased (t=24.162,t=17.314,P<0.05),and the expression levels of ASC and NLRP3 protein in kidney tissue were decreased (t=8.061,t=11.057,P<0.05). Conclusion: Febuxostat may play a kidney protective role in the hyperuricemia model rats by inhibiting the activation of NLRP3 inflammatory bodies and the levels of its downstream inflammatory factors.

Key words: febuxostat, hyperuricemia, nucleotide-binding oligomerization domain-like receptor protein 3, interleukin-1β, interleukin-18