大黄酸对糖尿病大鼠肾小管上皮细胞转分化的影响  

Effects of rhein on renal tubular epithelial cells transdifferentiation in diabetic rats

作　　者：金永东[1] 宁建平[1] 李文星[1] 曾莹晖[1] 陆小兰[1] 张义雄[1] 

机构地区：[1]中南大学湘雅医院肾内科,湖南长沙410008

出　　处：《中国医师杂志》2008年第4期483-486,共4页Journal of Chinese Physician

基　　金：湖南省科技攻关资助项目（05FJ3058,06SK3018）;湖南省中医药科研基金资助项目（24201）;

摘　　要：目的观察大黄酸对糖尿病大鼠肾小管上皮细胞-肌成纤维细胞转分化（EMT）的影响。方法雄性Wistar大鼠随机分为3组：正常对照组（N组，n=12）、糖尿病模型组（D组，／n=12）、糖尿病大黄酸干预组[R组，n=12，大黄酸100mg／（kg·d）灌胃]。成模后第8周末及16周末各组分别处死6只大鼠，测定24h尿蛋白排泄量、血肌酐；HE及MASSON染色法观察肾脏病理改变；免疫组织化学法检测E钙档蛋白（E-cad）、α平滑肌肌动蛋白（α-SMA）、纤连蛋白（FN）及转化生长因子13，（TGF-β1）的表达。结果（1）与N组比较，D组大鼠肾小管间质损伤指数、肾间质胶原面积明显增加（P〈0．01）；（2）D组大鼠肾小管上皮细胞E-cad阳性表达显著低于N组，α-SMA、FN和TGF-β1阳性表达均显著高于N组，E-cad表达和TGF-β1表达呈负相关（rs=-0．60，P〈0．05），α-SMA、FN表达和TGF-β1表达呈正相关（rs=0．88，P〈0．05；rs=0．91，P〈0．01）；（3）R纽大鼠肾小管间质损伤指数、肾间质胶原面积较D组明显减弱，其肾小管上皮细胞的E-cad的表达较D组明显增加，α-SMA、FN和TGF-β1表达较D组均明显减弱（P〈0．01）。结论大黄酸具有减轻糖尿病大鼠肾小管间质病变的肾脏保护作用，其机制可能与下调TGFβ1表达、阻抑EMT有关。Objective To study the effect of rhein on the process of tubular epithelial-mesenchymal transformation in kidney of diabetic rats. Methods Wistar male rats were randomly assigned to 3 groups ： Control group （ N group, n = 12）, diabetic group （ D group, n = 12）, rhein treatment group （R group, n = 12）. The rats of rhein treatment group were treated with daily intragastric administration of Rhein （ 100 mg/kg · d） after the models were successfully established. Six rats of each group were killed at the 8th and 16th week after experiment. The excretion of urinary protein and serum creatine were measured. Histological changes of renal tissue were observed by HE and MASSON stain. Immunohistochemistry was performed to investigate the expression of E-cadherin, α-SMA, FN and TGF-β1 in kidney. Results Compared with the control group, the tubulointerstitial injury and the accumulation of extracellular matrix protein in diabetic models were obvious（ P 〈0. 01 ）. Compared with the control group, the expression of E-cadherin was decreased significantly and the expression of c^-SMA, FN and TGF-β1 was increased significantly in diabetic group. E-cadherin was negatively correlated with TGF-β1（ rs = -0. 60, P 〈 0. 05）, α-SMA and FN was positively correlated with TGF-β1 （ rs =0. 88, P 〈0. 05; rs =0.91, P 〈0. 01 ）. In comparison with diabetic group, rhein could up-regulate the expression of E-cad and down-regulate the expression of α-SMA and FN in renal tubular epithelial cells （ P 〈 0. 01 ）. Conclusion Rhein could protect kidney by ameliorating interstitial fibrosis in diabetic rats. The mechanism may be depend on down-regulating the expression of TGF-β1 and suppressing tubular epithelial-mesenchymal transformation.

关 键 词：大黄酸/药理学 糖尿病 肾小管 上皮细胞 

分 类 号：R285.5[医药卫生—中药学]