STZ诱导糖尿病大鼠肾脏CTGF表达改变及意义探讨  

Expression of CTGF and its role in the streptozotocin-induced diabetic rat kidney

作　　者：黄海泉[1] 刘必成[1] 罗冬冬[1] 马坤岭[1] 刘殿阁[1] 刘宏[1] 

机构地区：[1]东南大学附属中大医院肾内科东南大学肾脏病研究所,江苏南京210009

出　　处：《中国病理生理杂志》2007年第3期553-558,共6页Chinese Journal of Pathophysiology

基　　金：江苏省基础研究计划(自然科学基金)资助项目(NoBK2002052);江苏省医学重点人才培养资助项目(NoRC2002072)

摘　　要：目的:观察STZ诱导糖尿病大鼠肾脏结缔组织生长因子(CTGF)表达改变及意义。方法:将SD大鼠分为对照(假手术)组(C组)(n=32)、糖尿病肾病组(DN组)(n=35)2组。每组再随机分为4个亚组:1周、2周、4周和8周组。观察各组大鼠血糖(BG)、24h尿量(UV)、体重(BW)、尿白蛋白排泄(24Ualb)、内生肌酐清除率(Ccr)、肾重(KW)、肾重/体重(KW/BW)、肾小球面积(AG)和体积(VG)、近端小管面积(AT)、GBM、TBM厚度的改变,免疫组化观察CTGF和α-SMA在小球、小管的表达情况。结果:实验期间DN组BG、UV明显大于C组(P<0.01),DN组24hUalb(mg/24h)、Ccr、KW、KW/BW、AG、VG、AT、小球及小管的CTGF表达均持续显著高于C组,AT在4周时达到高峰,且CTGF表达与24Ualb、AG、VG、AT等指标呈显著正相关(r分别=0.95、0.92、0.86、0.94,分别P<0.01、P<0.05)。α-SMA在DN组大鼠早期肾小管上皮细胞中表达不明显,第4周起可见少量α-平滑肌肌动蛋白(α-SMA)表达,到第8周时更明显。8周时DN组GBM和TBM明显厚于C组(P<0.01)。结论:糖尿病早期CTGF表达增加,并可能参与介导糖尿病早期肾脏肥大,CTGF可能与随后的肾小管上皮细胞转分化和肾脏纤维化有关。AIM： To investigate the change of connective tissue growth factor（CTGF） expression and its role in streptozotocin - induced diabetic rat kidney. METHODS： Male SD rats were randomly divided into two groups ： control （ sham operated rats, group C, n = 32） and diabetic rats （group DN, n = 35 ）. Rats in each group were sacrificed at 1, 2, 4, and 8 weeks respectively after induction of diabetes. Body weight（ BW）, blood glucose（ BG）, 24 - hour urine volumn （UV）, kidney weight, KW/BW,24 -hour urinary albumin excretion （24Ualb）, creatinine clearance （Ccr）, kidney weight （KW）, KW/BW, glomerular area （AG ） , proximal tubular area （A~） and the width of GBM ,TBM at each time point were measured. Expression of CTGF and α - SMA were detected by immunostaining. RESUILTS： There was a significant increase of 24 h Ualb, Ccr, KW/BW, AG, VG and the expression of CTGF in glomeruli and tubuli from week 1 onward in diabetic rats compared with those in group C （P 〈 0. 05, P 〈 0. 01, respectively）, and an increasing expression of α - SMA mainly located in dilated tubuli from week 4 was found in group DN, which was more evident at week 8 accompanied by the decrease in AT. Diabetic rats also had a significant increase in AT from week 1 onward, which peaked at week 4. CONCLUSION ： In the early stage of DN, the time - dependently upregulated CTGF might mediate the renal hypertrophy, which might be associated with the subsequent tubular epithelial -mesenchymal transdifferentiation （EMT） and renal fibrosis.

关 键 词：糖尿病 结缔组织生长因子 肾 纤维化 链脲菌素 

分 类 号：R363[医药卫生—病理学]