Ets-1转录因子在大鼠糖尿病肾病中的作用  

Role of the Ets-1 transcriptional factor in progression of diabetic nephropathy in rats

作　　者：陈涵枝[1,2] 刘殿阁[1,2] 周建东[2] 沈京群[2] 

机构地区：[1]哈尔滨医科大学附属第一医院肾内科,黑龙江哈尔滨150001 [2]东南大学附属中大医院肾内科,江苏南京210009

出　　处：《哈尔滨医科大学学报》2012年第4期340-345,共6页Journal of Harbin Medical University

摘　　要：目的观察转录因子Ets-1、基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-2组织抑制剂(TIMP-2)、平滑肌肌动蛋白(α-SMA)及Ⅳ型胶原(ColⅣ)在实验性糖尿病肾病(DN)进程中的表达及意义。方法雄性SD大鼠随机分成对照组(NC组,n=30);糖尿病组(DM组,n=40),腹腔注射链脲佐菌素(STZ)诱导糖尿病动物模型。STZ注射后第1、4、8、12、16周分别处死各实验组动物6～8只,采用免疫组化观察各组大鼠肾内Ets-1、MMP-2、TIMP-2、α-SMA及ColⅣ表达,并进行免疫双染共定位分析。结果免疫组化表明,同NC组相比,DM组Ets-1在肾小球、肾小管间质的表达于STZ注射后第1周明显增加(P<0.05),至第4、8周分别达到高峰(P<0.05),随后呈下降趋势,16周降至最低(P>0.05)。MMP-2在肾小球内的表达与Ets-1在肾小球内的表达相似;DM组TIMP-2在肾小球及肾小管间质的表达于STZ注射后第1周开始增加,第16周升至最高(P<0.01);肾小球内MMP-2/TIMP-2比率于STZ注射后第1周显著性升高(P<0.01),第4周起明显下降(P<0.01),第12、16周时甚至低于相同时间点NC组大鼠,有显著性统计学差异(均P<0.01),而肾小管间质内MMP-2/TIMP-2比率于STZ注射后第4周开始明显降低(P<0.05),并且随病程进展进一步下降;DM组ColⅣ在肾小球及肾小管间质内的沉积于STZ注射后第1周开始增加,第16周达高峰(P<0.05)。α-SMA在肾小球内及肾小管间质的表达于STZ注射后第1周开始增加,并且随病程进展逐渐增加,第16周升至最高(P<0.05)。相关分析表明,DM组肾小球及肾小管间质内Ets-1表达与MMP-2的表达呈显著正相关(r=0.856,P<0.01;r=0.642,P<0.01),而与MMP-2/TIMP-2比率呈负相关(r=-0.549,P<0.01;r=-0.580,P<0.01);MMP-2/TIMP-2比率与ColⅣ的表达呈显著负相关(r=-0.701,P<0.01;r=-0.626,P<0.01)。免疫双染显示,Ets-1阳性的肾小球固有细胞及肾小管间质细胞同时出现MMP-2阳性表达,TIMP-2染色阳性的肾小球固有细胞及肾小管间质细胞同时具有α-To study the role of the expression pattern of Ets-1, matrix metalloproteinase-2 （ MMP-2）, tissue inhibitor of metalloproteinase-2 （ TIMP-2 ）, a-smooth muscle ac- tion （ot-SMA） and type IV collagen （Col Ⅳ ） in matrix remodeling in experimental diabetic nephropathy. Methods Male Spregue-Dawley rats were randomly divided into two groups： normal control group （ NC group, n = 30 ）, and diabetes mellitus group （ DM group, n = 40 ）, which intraperitoneally injected with streptozotozin （STZ）. Then 6 - 8 rats of each group were sacrificed at week 1, week 4, week 8, week 12 and week 16 after injection. Ets-1, MMP-2, TIMP-2, ot-SMA and Col IV expression in rat kidneys were observed by using immunohisto- chemistry and immune double staining co-localization analysis. Results By immunohistochem- istry, the expression of Ets-1 in glomeruli and tubulointerstitium were significantly increased in the rat kidneys post-STZ injection from week 1 （P 〈 0.05） and reached the peak at week 4 （P 〈 0. 05 ）, at week 8 （P 〈 0. 05 ）, which followed a downward trend and reached a minima at week 16 compared with NC group. The expression of MMP-2 in glomeruli showed a similar pat- tern like the expression of Ets-1. The expression of TIMP-2 in glomeruli and tubulointertitium showed increasing from week 1 and reached a maxima at week 16 （P 〈0.01 ）. Specially, the ratio of MMP-2 and TIMP-2 in glomeruli began to increase at week 1 （P 〈0. 01 ） in STZ-trea- ted rat kidneys, then decreased from week 4 to week 16, and even lower than the NC rats from week 12 to week 16 with different significance, while the ratio of MMP-2 and TIMP-2 in tubu- lointertitium showed decreasing from week 4 to week 16 （P 〈 0. 05, respectively）. The deposi- ton of Col Ⅳ in glomeruli and tubulointerstitium showed increasing from week 1 and reached a maxima at week 16 after STZ injection （P 〈 0.05 ）. The expression of ot-SMA in glomeruli and tubulointerstitium began to increase from week 1 and reached t

关 键 词：糖尿病肾病 免疫组织化学 ETS-1 基质金属蛋白酶-2 基质金属蛋白酶-2组织抑制剂 Ⅳ型胶原 

分 类 号：R692[医药卫生—泌尿科学] R-332[医药卫生—外科学]