慢性肾衰幼年大鼠肾小管上皮细胞转分化的分子表型及干预研究  

Molecular phenotype of epithelial mesenchymal transition and its treatment in young rats with chronic renal gailure

作　　者：李小琴[1] 马宏[1] 赵健玲[1] 李卫卫[1] 赵晓华[1] 武艳[1] 李娟[1] 王亚娟[1] 

机构地区：[1]山西医科大学第一临床医学院儿科,太原030001

出　　处：《山西医科大学学报》2009年第4期312-315,共4页Journal of Shanxi Medical University

基　　金：山西省高校科技研究开发基金资助项目(2003103)

摘　　要：目的探讨5/6肾切除残肾慢性肾衰幼年大鼠慢性进展性肾小管间质纤维化形成过程中,肾小管上皮细胞转分化(EMT)的相关蛋白a-平滑肌肌动蛋白(α-SMA)和E-钙黏蛋白(E-cadherin)的动态表达趋势。方法72只3-4周龄幼年SD雌性大鼠,随机将其分为假手术组(n=24)、5/6NX未治疗组(n=24)和5/6NX治疗组(n=24)。采用5/6肾切除法制备慢性残肾肾衰模型,采用免疫组化染色法于模型成功后第2,4,8,12周分别检测残肾组织中α-SMA、E-cadherin的表达。结果随着实验时间的延长,5/6NX未治疗组肾小管间质病变日趋明显,表现为组织中炎性细胞浸润,肾小管上皮细胞肿胀,肾小管塌陷及肾小管间隙加宽,并进行性形成纤维化病变。随着实验时间的延长,α-SMA在5/6NX未治疗组和治疗组中表达强度均呈增高趋势,除第2周外,相同时间点α-SMA在各组的表达强度差异具有统计学意义(P<0.05),在未治疗组表达最高,治疗组次之,假手术组最低。随着实验时间的延长,E-cadherin在5/6NX未治疗组和治疗组中表达强度均呈降低趋势,除第2周外,相同时间点E-cadherin在各组的表达强度差异具有统计学意义(P<0.05),在未治疗组表达最低,治疗组次之,假手术组最高。结论5/6肾切除残肾慢性肾衰幼年大鼠在其肾损伤过程中存在EMT现象,α-SMA和E-cadherin是EMT的标志性蛋白,给予ACEI和ARB干预具有一定的治疗效应。Objective To investigate expression of epithelial mesenchymal transition（EMT） -related proteins α-SMA and E-cadherin at different time points in chronic progressive renal tubulointerstitial fibrosis of remnant kidney 5/6 nephrectomized young rats. Methods Seventy-two young female 3 -4 week-old SD rats were randomized into sham operation group （n = 24） ,5/6NX untreated group （n = 24） and 5/6NX treated group （treated with ACEI and ARB, n = 24）. Five sixth of kidney of rats in 5/6NX untreated group and 5/6NX treated group were cut off to make chronic renal failure model. The expression of α-SMA and E-cadherin was detected by immunohisto- chemical staining in remnant kidney at week 2,4,8 and 12 after establishing the model. Results In 5/6NX untreated group,the tu- bulointerstitial lesions progressively developed the fibrosis following the experimental time, with infiltrating of inflammatory cells in tis- sues, swelling of tubular epithelial ceils, collapsing of renal tubules and widening of renal tubules space. The expression of α-SMA gra- dually increased during the experiment in 5/6NX untreated group and 5/6NX treated group, and there was significant difference at week 4,8,12 between 2 groups（ P 〈 0.05 ）. The expression of α-SMA in 5/6NX treated group was significantly lower than in 5/6NX untreat- ed group, and higher than in sham operation group at week 4,8,12 （P 〈 0.05 ）. The expression of E-cadherin gradually decreased dur- ing the experiment in 5/6NX untreated group and 5/6NX treated group, and there was significant difference at week 4,8,12 between 2 groups（P 〈0.05）. The expression of E-cadherin in 5/6NX treated group was significantly higher than in 5/6NX untreated group,and lower than in sham operation group at week 4,8,12 （ P 〈 O. 05 ）. Conclusion EMT participates in progressive tubulointerstitial fibro- sis in remnant kidney of 5/6 nephrectomized young rats,and α-SMA and E-cadherin are the markers of EMT. ACEI and ARB have a protective effect on EMT.

关 键 词：5/6肾切除幼年大鼠 肾小管上皮细胞转分化 Α-SMA E—cadherin 肾小管间质纤维化 

分 类 号：R692.5[医药卫生—泌尿科学]