丹参酮ⅡA对高糖诱导肾小管上皮细胞转分化中Wnt/β-catenin信号途径的影响  

Effects of Tanshinone ⅡA on Wnt/β-catenin Signaling Pathway of High Glucose Induced Renal Tubular Epithelial Cell Transdifferentiation

作　　者：黄宝英[1] 曹罗元[1] 富显果[1] 刘金发[1] 杨菁[1] 陈刚[2] 

机构地区：[1]福建中医药大学附属宁德市医院,福建352100 [2]福建省立医院,福州350001

出　　处：《中国中西医结合杂志》2012年第7期965-969,共5页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：福建省自然科学基金科技项目(No.2012J01435);福建省宁德市卫生类科技计划项目(No.20100144)

摘　　要：目的探究高糖诱导肾小管上皮细胞转分化过程中Wnt/β-catenin信号途径的表达及丹参酮ⅡA对其影响。方法将人近端肾小管上皮细胞(HK-2),分为正常糖组(NG组)、高糖组(HG组)、高糖+丹参酮ⅡA干预组(HG+T组)。采用免疫细胞化学观察β-catenin表达情况;Western印迹检测β-catenin、上皮细胞标志性蛋白E-钙粘蛋白(E-cadherin)、间充质细胞标志性蛋白α-SMA的表达;RT-PCR检测β-cate-nin、E-cadherin mRNA表达水平。结果与NG组比较,HG组β-catenin蛋白及mRNA表达显著增强(P<0.01),E-cadherin表达显著降低(P<0.01),β-catenin蛋白在胞浆与胞核表达增强。终浓度为100μmol/L的丹参酮ⅡA可显著减少β-catenin的异位表达;在该浓度下,β-catenin在胞核蛋白及mRNA的表达量显著下降,而E-cadherin蛋白及mRNA的表达水平上升,同时间充质细胞标志性蛋白α-SMA的表达明显下降。结论 Wnt/β-catenin信号途径参与了高糖诱导肾小管上皮细胞转分化过程,丹参酮ⅡA可能通过下调Wnt/β-catenin信号途径的活性而抑制转分化过程,进而发挥保护肾脏的作用。Objective To observe the expressions of Wnt/13-catenin and the effects of tanshinone IIA （TII A） on Wnt/13-catenin signaling pathway in high glucose induced renal tubular epithelial cell transdifferentiation. Methods Human kidney proximal tubular epithelial cells （HK-2） were divided into three groups, i.e., the normal glucose group, the high glucose group, and the high glucose plus tanshinone I[A group. The expression of 13-cate- nin was observed using immunocytochemical staining. The protein expression of 13-catenin, E-cadherin, and c（- smooth muscle actin （cx-SMA） were detected by Western blot. The mRNA levels of 13-catenin and E-cadherin were detected by RT-PCR. Results Compared with the normal glucose group, both the protein and the mRNA expres- sions of 13-catenin were significantly enhanced （ P 〈 O. 01 ）, the expression of E-cadherin significantly decreased （ P 〈0.01 ）, the expression of 13-catenin increased in the cytoplasm and nucleus in the high glucose group. TIIA at the final concentration of 100 iJmol/L significantly reduced the ectopic expression of 13-catenin. At that concentra- tion, the protein and mRNA expressions of {3-catenin in the nucleus significantly decreased, while the protein and mRNA expressions of E-cadherin were up-regulated. Meanwhile, the expression of c（-SMA obviously decreased. Conclusions Wnt/βcatenin signaling pathway participated in the high glucose induced renal tubular epithelial cell transdifferentiation. TII A inhibited the transdifferentiation process possibly through down-regulating the activities of Wnt/iB-catenin signaling pathway, thus further playing a role in renal protection.

关 键 词：E-钙粘蛋白 Β-连环蛋白 Α-平滑肌肌动蛋白 上皮细胞转分化 丹参酮ⅡA 

分 类 号：R692[医药卫生—泌尿科学]