Db/db小鼠肾脏中Tribble3的表达及其与肾脏纤维化的关系  

Expression of Tribble3 in db/db mice renal tissues and the possible role in renal fibrosis

作　　者：张锦航[1] 张鲁伟[1] 刘新农[2] 田军[1] 

机构地区：[1]山东大学齐鲁医院血液净化中心,济南250012 [2]山东大学齐鲁医院普外科,济南250012

出　　处：《山东大学学报（医学版）》2014年第2期38-43,共6页Journal of Shandong University:Health Sciences

基　　金：国家自然科学基金(81000303);山东省自然科学基金(ZR2009CQ036)

摘　　要：目的探讨假性激酶Tribble3(TRB3)在db/db小鼠不同阶段肾脏组织中的表达及其与糖尿病肾病(DN)所致肾脏纤维化的关系。方法 12周龄雄性db/db小鼠15只为模型组(DN),db/m小鼠15只为对照组(C)。每周监测随机血糖,分别在16、20、25周龄取材并检测体质量(WB)、24 h尿蛋白量(UAE)、血肌酐(Scr)、尿素氮(BUN)。通过苏木精-伊红(HE)染色、高碘酸-无色品红(PAS)染色、马松三色(Masson)染色观察肾组织病理改变,并检测肾小球系膜基质相对面积和间质纤维化程度,免疫组化法检测TRB3在肾组织中的表达,RT-PCR、Western blotting分别检测TRB3、转化生长因子-β1(TGF-β1)mRNA及蛋白水平的变化。结果与同周龄C相比,DN的UAE、Scr和BUN均明显升高(P<0.05,P<0.01);肾小球系膜及基底膜相对面积在20、25周龄时差异有统计学意义(P<0.01),肾间质纤维组织相对面积在16、20、25周龄时差异均有统计学意义(P<0.01);20周DN的TRB3 mRNA及蛋白、TGF-β1mRNA与25周DN的TRB3、TGF-β1 mRNA及蛋白水平均显著升高(P<0.05,P<0.01),且均随病程进展呈上升趋势;相关性分析结果显示,DN的TRB3蛋白表达与TGF-β1表达水平呈正相关(r=0.944,P<0.01),与肾间质纤维化程度呈正相关(r=0.857,P<0.05)。结论与同周龄db/m小鼠相比,TRB3在db/db小鼠的肾脏组织中表达量升高,且与纤维化因子TGF-β1的表达量及间质纤维化程度具有正相关性。Objective To investigate the expression of Tribble3 in renal tissues of db/db mice at different stages and its relationship with renal fibrosis in diabetic nephropathy （DN）. Methods A total of 15 12-week-old male db/db mice and 15 age-matched control db/m mice were enrolled in the study. Random blood glucose and body weight were detec- ted weekly. Animals were divided into 3 groups and sacrificed at 16wk, 20wk and 25wk respectively. The weight of body （ WB）, 24 h urinary albumin excretion （ UAE）, serum creafinine （Scr） and blood urea nitrogen （BUN） were detected before death. Renal tissue was harvested for histologic staining to evaluate the morphologic change, and immu- nohistochemical staining to detect the expression of TRB3. Real time-PCR and Western blotting were used to quantify the TRB3 and TGF-β1 expression at mRNA and protein levels respectively. Results Levels of UAE, Scr and BUN of db/db mice were higher than those of the controls （P 〈0. 05, P 〈0.01 ）. The relative area of rnesangium matrix andthe content of collage in db/db mice were increased significantly from 20wk compared with those of the controls （ P 〈 0.01 ）. The relative area of interstitial fibrous tissue was statistically different at 16wk, 20wk, and 25wk （P 〈0.01 ）. Expression of TRB3 and TGF-β1 in renal tissue of db/db mice increased from 20wk and showed significant difference between the two groups at 25wk. The expression of TRB3 was positively correlated with TGF-β1 protein （ r = 0. 944, P 〈 0.01 ） and renal interstitial fibrosis （ r = 0. 857, P 〈 0.05 ） in the DN group. Conclusion Compared with the age- matched db/m mice, TRB3 expression increases significantly in the kidney of db/db mice and has positive correlation with renal fibrosis induced by DN.

关 键 词：糖尿病肾病 Tribble3 DB db小鼠 转化生长因子一131 纤维化 

分 类 号：R692.9[医药卫生—泌尿科学]