萝卜硫素基于Nrf2/ARE通路改善肾病综合征幼鼠的肾功能

The sulforaphane is based on the Nrf2/ARE pathway to improve renal function in nephrotic syndrome young rats

目的探讨萝卜硫素(SF)能否通过上调核因子NF-E2相关因子(Nrf2)发挥缓解炎症并改善肾病综合征的作用。方法将3周龄雄性SD幼鼠随机均分为4组,Con组(对照组)、Model组(模型组)、SF组(萝卜硫素组)和SF溶剂组,SF组腹腔注射SF15 mg·kg^(-1),SF溶剂组腹腔注射等体积的生理盐水作为溶媒对照,每天2次,间隔8 h,连续注射3 d;第4天Model组、SF组和SF溶剂组均给予多柔比星(Dox),尾静脉2次给药(4.0、2.5 mg·kg^(-1)),2次间隔1周,Con组在相同处理条件下注射等体积的生理盐水。收集尿液和血液,ELISA法检测尿蛋白、血清白蛋白、白细胞介素-18(IL-18)和白细胞介素-1β(IL-1β);分离肾脏组织用于HE染色,Western blot检测肾脏组织Nrf2核蛋白表达。结果Model组与SF溶剂组肾损伤严重,损伤评分、尿蛋白、血清白蛋白、IL-18和IL-1β水平均明显高于Con组,并且Nrf2蛋白表达上调(P<0.05);与SF溶剂组比较,SF预处理后,幼鼠肾功能损伤改善,损伤评分、尿蛋白、血清白蛋白、IL-18和IL-1β水平降低,Nrf2蛋白表达水平上调(P<0.05);Model组与SF溶剂组上述各项指标差异无统计学意义(P>0.05)。结论SF通过诱导Nrf2蛋白表达降低尿蛋白、血清白蛋白、IL-18和IL-1β水平,缓解了Dox诱导肾病综合征的严重程度。

Objective To explore whether sulforaphane(SF)can relieve inflammation and improve nephrotic syndrome by up-regulating nuclear factor-erythroid 2-related factor 2(Nrf2).Methods 3-week-old SD rats were randomly and equally divided into 4 groups,i.e.control group,model group,SF group and SF solvent group.The SF group and the SF solvent group were intraperitoneally injected with 15 mg·kg^(-1)SF and an equal volume of normal saline respectively,twice per day,interval 8 hours,consecutive injection for 3 days.On the 4 th day,model group,SF group and SF solvent group were given(4.0,2.5 mg·kg^(-1))doxorubicin(Dox)by tail vein injection,twice at an interval of 1 week,while the control group were injected with the same volume of saline.Urine and blood were collected,and the urine protein,serum albumin,IL-18 and IL-1βwere detected by ELISA.Kidney tissue was separated for HE staining,and Western blotting was used to detect the expression of Nrf2 protein.Results Rats in the model or SF solvent group showed more severe kidney damage.The damage score,urine protein,serum albumin,IL-18 and IL-1βlevels in the model or SF solvent group were significantly higher than those in the control group,and with the higher expression of Nrf2 protein(P<0.05).Compared with the solvent group,SF pretreatment improved the renal functional damage,and reduce the damage score,urine protein,serum albumin,the levels of IL-18 and IL-1β,increased the level of Nrf2 protein(P<0.05).There was no significantly statistical difference in the above indicators between the model and the SF solvent group(P>0.05).Conclusion SF reduces urine protein,serum albumin,IL-18 and IL-1βby inducing the expression of Nrf2 protein,thereby alleviates the severity of Dox-induced nephrotic syndrome.