Notch1/Jagged1在高尿酸血症导致早期慢性肾损伤中的作用  

The roles of Notch1/Jagged1 in early stage of hyperuricemia-induced chronic renal injury

作　　者：沈育丽[1] 张文彬[1] 傅君舟[1] 梁鸣[1] 陈敢[1] 李慧娟[1] 周姗姗[1] 

机构地区：[1]广州医学院附属广州市第一人民医院肾内科,510180

出　　处：《广东医学》2013年第6期827-830,共4页Guangdong Medical Journal

基　　金：广东省科技计划项目(编号:2010B080702020)

摘　　要：目的探讨Notch1/Jagged1在高尿酸血症导致大鼠早期慢性肾损伤中的作用。方法雄性SD大鼠21只随机分为正常组(n=7)、模型组(n=7)和DAPT干预组(n=7),采用氧嗪酸和尿酸联合制作高尿酸血症模型,Notch信号通路特异性抑制剂γ-分泌酶抑制剂(DAPT)进行特异性干预,定期监测生化指标直至造模6周。比较各组间血尿酸(UA)、血尿素氮(BUN)、血肌酐(Scr)水平,HE染色观察各组大鼠肾脏损伤情况,同时采用免疫组化染色比较各组间Notch1、Jagged1表达情况。结果造模6周后,模型组UA、BUN、Scr、Notch1、Jagged1显著升高(P<0.01)。与模型组相比,DAPT干预组BUN、Scr、Notch1、Jagged1明显降低(P<0.05)。结论在高尿血酸血症动物模型中发现Notch1、Jagged1表达升高,DAPT干预后可改善肾功能,延缓慢性肾损伤进展。Notch1/Jagged1在高尿酸血症所致早期慢性肾损伤中起着重要作用。Objective To investigate the roles of Notchl/Jaggedl in early stage of hyperuricemia - induced chronic renal injury in rats. Methods Twenty one Sprague - Dawley rats were randomly assigned to control group （ n = 7 ）, hyperuricemia model group （ n = 7 ）, and DAPT treatment group （ n = 7 ）. Oxonie acid and Uric acid were used to establish the hyperuricemia model. Meanwhile, the inhibitor of notch signaling, γ- secretase inhibitor （DAPT） , was given in DAPT treatment group. Biochemical indices, including serum uric acid （UA）, blood urea nitrogen （BUN） and serum creatinine （Scr） , were regularly monitored until 6 weeks after hyperuricemia model established. Hematoxylin - eosin （HE） was applied for observation of histopathological injury. The expression of Notchl and Jaggedl were assessed and compared. Results Significant elevation of UA, BUN and Scr, as well as the up - regulation of Notchl and Jaggedl were observed in hyperuricemia model group as compared with the control group （ P 〈 0. 01 ）. However, comparing with the hyperuricemia model group, significant alleviation in BUN and Scr, as well a the down -regulation of Notchl and Jaggedl were revealed in DAPT treatment group （P 〈 0. 05 ）. Conclusion The Notchl and Jaggedl are up - regulated in rat hy- peruricimia models. The treatment of DAPT can ameliorate renal function, and postpone the progress of chronic renal injury. Notchl and Jaggedl play important roles in early stage hyperuricemia- induced chronic renal injury.

关 键 词：高尿酸血症 NOTCH1 JAGGED1 慢性肾损伤 

分 类 号：R971.1[医药卫生—药品]