冬虫夏草菌丝对糖尿病大鼠肾脏DKK1、β-catenin表达的影响  

Effects of Cordyceps sinensis on expressions of DKK1 and β-catenin in diabetic rats

作　　者：杜月娟[1] 刘元涛[2] 卢圣霞[1] 刘晔[1] 齐文文[1] 傅余芹[1] 

机构地区：[1]山东大学第二医院肾脏内科,济南250033 [2]山东大学第二医院内分泌科,济南250033

出　　处：《山东大学学报（医学版）》2012年第6期26-30,37,共6页Journal of Shandong University:Health Sciences

基　　金：山东省自然科学基金资助项目(Y2006C36)

摘　　要：目的研究冬虫夏草菌丝对糖尿病大鼠肾脏纤维连接蛋白(FN)、Dickkopf-1(DKK1)及β-连环蛋白(β-catenin)表达的影响,探讨其作用效果及机制。方法 Wistar大鼠40只,随机取12只为对照组,28只用链脲佐菌素造模。24只建模成功,随机分为非治疗组(n=12)和虫草菌丝治疗组(n=12)。12周末处死各组大鼠,测定血糖、尿白蛋白肌酐比(UACR)和内生肌酐清除率(Ccr);应用免疫组化、实时荧光定量PCR观察大鼠肾脏DKK1、β-catenin和FN表达的变化;应用Western blot检测DKK1的表达。结果与对照组相比,非治疗组和虫草菌丝治疗组大鼠UACR和Ccr明显升高(P<0.05)。免疫组化和PCR结果显示,FN、DKK1 mRNA及蛋白表达明显上调(P<0.05)。与非治疗组相比,治疗组大鼠UACR和Ccr显著降低(P<0.05),FN、DKK1 mRNA及蛋白表达减少(P<0.05)。非治疗组β-catenin蛋白表达较对照组明显减少(P<0.05),治疗组β-catenin蛋白表达明显高于非治疗组(P<0.05)。结论冬虫夏草对糖尿病大鼠肾脏FN表达具有抑制作用,其机制可能与抑制DKK1、稳定β-catenin有关。Objective To stu-dy the effects of Cordyceps sinensis on expression of fibronectin （FN） , Dickkopf-1 （ DKK1 ） and β-catenin in the kidney of diabetic rats, and to investigate the mechanisms underlying. Methods Diabe- tes was induced in Wistar rats by intraperitoneal injection of Streptozotocin （60 mg/Kg）. Diabetic rats were randomly divided into the none-treatment group （n = 12 ） and the Cordyceps treatment group （n = 12 ）. None diabetic Wistar rats were used as controls （n = 12）. After 12 weeks, the rats were sacrificed. The level of blood glucose, urinary albumin to creatinine ratio （UACR） and creatinine clearance rate （Ccr） were determined. The protein and mRNA levels of DKK1,β-catenin and FN were evaluated by immunohistochemistry and real-time PCR. DKK1 protein expression was further examined by western blot. Results Compared with control group, the levels of UACR and Ccr in no treatment group and Cordyceps treatment group were significantly increased（ P 〈 0.05 ）, the mRNA and protein levels of FN and DKK1 were significantly elevated （ P 〈 0.05 ）. Compared to no treatment group, the levels of UACR and Ccr in Cordyceps treatment group were decreased, the mRNA and protein levels of FN and DKK1 were reduced（ P 〈 0.05 ）.Compared with control group, β-catenin expression was significantly reduced in none-treatment group as demonstrated by immunostaining （P 〈 0.05 ） ; while β-catenin expression was significantly higher in Cordyceps-treatment group com- pared with no treatment group （P 〈 0.05）. Conclusion Cordyceps sinensis may reduce the excessive accumulation of FN in the kidney of diabetic rats through suppressing DKK1 expression and stabilizing β-catenin protein.

关 键 词：糖尿病肾病 冬虫夏草 DICKKOPF-1 Β-连环蛋白 纤维连接蛋白 大鼠 WISTAR 

分 类 号：R587.1[医药卫生—内分泌]