Liu Bi-cheng, Huang Hai-quan, Luo Dong-dong, Ma Kun-ling, Liu Dian-ge, Liu Hong
Institute of Nephrology, Zhong Da Hospital, Southeast University, Nanjing 210009, China.
Chin Med J (Engl). 2006 Jun 20;119(12):1010-6.
Renal hypertrophy has been regarded as the early feature of diabetic nephropathy (DN), which may eventually lead to proteinuria and renal fibrosis. However, the exact mechanism of renal hypertrophy is still unclear. The aim of this study was to investigate the possible association of connective tissue growth factor (CTGF) with renal hypertrophy in uninephrectomized diabetic rats.
Seventy-two Sprague-Dawley (SD) rats were randomly divided into two groups: control group (group C, n = 32) and diabetic nephropathy (group DN, n = 40). Each group was re-divided into 4 subgroups according to the experimental period. The rats were sacrificed at 1, 2, 4, and 8 weeks respectively after induction of diabetes. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ) after rats had received uninephrectomy. Blood glucose (BG), body weight (BW), 24-h urinary albumin excretion (24hUalb), kidney weight (KW), KW/BW, glomerular tuft area (AG), glomerular tuft volume (VG), proximal tubular area (AT) at each time point, the width of glomerular basement membrane (GBM) and tubular basement membrane (TBM) at week 8 were measured when the rats were sacrificed. Renal expression of CTGF and p27kip1 were detected by immunohistochemical staining. The relationship between CTGF expression and increasing of VG and AT was analyzed.
There was a significant increase of 24hUalb, KW, and KW/BW from week 1 onward in diabetic rats compared to those in group C (P < 0.05, respectively), diabetic rats also had a significant increase of AG, VG, and AT from week 1 onward. It was also shown that diabetic rats had a thickening of GBM [(245.7 +/- 103.0) nm vs (121.8 +/- 19.1) nm, P < 0.01] and TBM [(767.7 +/- 331.1) nm vs (293.0 +/- 110.5) nm, P < 0.01] at week 8. There was a weak expression for CTGF and p27kip1 in normal glomeruli and tubuli, while a significant increasing expression of CTGF and p27kip1 was found in glomeruli and tubuli in diabetic kidney from week 1 onward (P < 0.05, respectively), and the extent of CTGF expression was positively correlated with AG (r = 0.92, P < 0.05), VG (r = 0.86, P < 0.05), AT (r = 0.94, P < 0.01) and positively correlated with the expression of p27kip1 (r = 0.96, P < 0.01).
The expression of CTGF increases in diabetic rat kidney at the early stage, which might be an important mediator of renal hypertrophy through arresting cell cycling.
肾肥大被视为糖尿病肾病（DN）的早期特征，最终可能导致蛋白尿和肾纤维化。然而，肾肥大的确切机制仍不清楚。本研究旨在探讨结缔组织生长因子（CTGF）与单侧肾切除糖尿病大鼠肾肥大之间的可能关联。
72只Sprague-Dawley（SD）大鼠随机分为两组：对照组（C组，n = 32）和糖尿病肾病组（DN组，n = 40）。每组根据实验周期再分为4个亚组。糖尿病诱导后分别于1、2、4和8周处死大鼠。大鼠单侧肾切除后通过腹腔注射链脲佐菌素（STZ）诱导糖尿病。处死大鼠时测量各时间点的血糖（BG）、体重（BW）、24小时尿白蛋白排泄量（24hUalb）、肾脏重量（KW）、KW/BW、肾小球簇面积（AG）、肾小球簇体积（VG）、近端肾小管面积（AT），以及第8周时的肾小球基底膜（GBM）宽度和肾小管基底膜（TBM）宽度。通过免疫组织化学染色检测肾脏中CTGF和p27kip1的表达。分析CTGF表达与VG和AT增加之间的关系。
与C组相比，糖尿病大鼠从第1周起24hUalb、KW和KW/BW显著增加（P均< 0.05），糖尿病大鼠从第1周起AG、VG和AT也显著增加。还显示糖尿病大鼠在第8周时GBM增厚[（245.7 ± 103.0）nm对（121.8 ± 19.1）nm，P < 0.01]和TBM增厚[（767.7 ± 331.1）nm对（293.0 ± 110.5）nm，P < 0.01]。正常肾小球和肾小管中CTGF和p27kip1表达较弱，而糖尿病肾的肾小球和肾小管中从第1周起CTGF和p27kip1表达显著增加（P均< 0.05），CTGF表达程度与AG（r = 0.92，P < 0.05）、VG（r = 0.86，P < 0.05）、AT（r = 0.94，P < 0.01）呈正相关，与p27kip1表达呈正相关（r = 0.96，P < 0.01）。
糖尿病大鼠肾脏早期CTGF表达增加，可能是通过阻止细胞周期而成为肾肥大的重要介质。
