NLRP3在马兜铃酸致肾损伤小鼠肾脏组织中的表达及其意义

Expression of NLRP3 in kidney tissue of mice with acute renal failure induced by aristolochic acid-1and its significance

目的:探讨核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)在马兜铃酸致肾损伤小鼠肾脏组织中的表达及意义,阐明NLRP3在马兜铃酸所致肾病发生发展过程中的作用。方法:64只雄性ICR小鼠随机分为对照组(16只)和马兜铃酸组(48只),马兜铃酸组小鼠给予50、100和200mg·kg-1马兜铃酸灌胃,每组16只。连续灌胃3d,于给药后第4和8天每组分别处死8只动物,收集尿液和血清,测定24h尿蛋白和血肌酐、尿素氮水平;ELISA法检测血清中白细胞介素1β(IL-1β)和白细胞介素18(IL-18)水平;荧光定量PCR检测肾组织中NLRP3mRNA的表达水平。结果:给药第4和8天,与对照组比较,马兜铃酸组小鼠24h尿蛋白、血肌酐和尿素氮均显著下降(P<0.05),其中200mg·kg-1马兜铃酸组小鼠在第7天全部死亡;与对照组比较,马兜铃酸组小鼠血清IL-1β和IL-18含量均显著升高(P<0.05),肾脏NLRP3的表达水平亦显著升高(P<0.05),且200mg·kg-1马兜铃酸组NLRP3表达水平显著高于50mg·kg-1马兜铃酸组(P<0.05)。结论:小鼠肾脏组织中NLRP3表达上调可能与马兜铃酸所致小鼠急性肾损伤的病理过程有关。

Objective To investigate the expression of nucleotide-binding and oligomerization domain（NOD）-like receptor 3（NLRP3）in kidney tissue of mice with acute renal failure induced by aristolochic acid-1（AA）and its significance,and to clarify the role of NLRP3in the development of AA-induced nephropathy.Methods Male ICR mice were randomly divided into control group and AA group.The mice in AA group received AA by gavage at doses of 50,100and 200mg·kg-1 daily and lasted for 3d.There were 16mice in each group.4and 8dafter administration,8mice of each group were killed respectively and urinary and serum were collected to detect 24h urinary protein,serum creatinine and urea nitrogen levels.The IL-1βand IL-18levels in serum were measured by ELISA kits.Moreover,real-time PCR was used to examine the mRNA expression of NLRP3in kidney tissue.Results Compared with control group,the 24hurinary protein,serum creatinine and serum BUN of the mice in AA group were significantly decreased 4and 8dafter administration（P0.05）,and the mice in 200mg·kg-1 AA group were death at day 7.Compared with control group,the IL-1βand IL-18levels in serum of the mice in AA group were significantly increased（P0.05）,and the mRNA expression of NLRP3in kidney tissue was also up-regulated（P0.05）.Moreover,the expression level of NLRP3in 200mg·kg-1 AA group was significantly higher than that in 50mg·kg-1 AA group（P0.05）.Conclusion The up-regulation of NLRP3in kidney tissue of the mice may participate in the pathological process of actue renal failure induced by AA.