Role of connective tissue growth factor in experimental radiation nephropathy in rats

作     者：LIU Dian-ge WANG Tie-min 

作者机构：Department of Nephrology Zhongda Hospital Southeast University School of Medicine Nanjing Jiangsu 210009 China Department of Pediatrics Fourth Clinical Hospital HarbinMedical University Harbin Heilongjiang 150001 China 

出 版 物：《Chinese Medical Journal》 (中华医学杂志（英文版）)

年 卷 期：2008年第121卷第19期

页      面：1925-1931页

核心收录：

学科分类：1002[医学-临床医学] 100210[医学-外科学(含：普外、骨外、泌尿外、胸心外、神外、整形、烧伤、野战外)] 10[医学] 

主　　题：connective tissue growth factor collagen radiation nephropathy glomerulosclerosis tubulointerstitial fibrosis 

摘      要：Background Connective tissue growth factor （CTGF） is a potent fibrogenic cytokine which has been associated with progressive glomerulosclerosis and tubulointerstitial fibrosis. We investigated the role of CTGF on the progression of a rat model of radiation nephropathy. Methods The model of radiation nephropathy in rats was established as follows： control group （n=12）, underwent only laparotomy; irradiated group （n=-20）, underwent a laparotomy, then the rats were subjected to a single dose 25 Gy X-ray to the kidneys. The rats were followed up one, three, six and nine months after renal exposure to radiation. Results Renal dysfunction was noted early in irradiated rats. Histological analysis showed focal glomerular sclerotic lesions at an early stage after irradiation. Radiation-induced glomerular and tubulointerstitial injuries were particularly severe the sixth month after irradiation as compared to the control group （P 〈0.01）. By immunohistochemistry, increased expression of CTGF was noted in the irradiated kidneys, which began to increase from the first month after irradiation, and remained significantly higher at the sixth and ninth month after irradiation （P 〈0.01）. Upon Western blot analysis CTGF protein expression showed an increase in the radiation treated kidneys compared with the control rats. The expression of CTGF closely correlated with the progression of radiation nephropathy. The expression of α-smooth muscle actin, vimentin, type Ⅲ collagen and type Ⅳ collagen was also high in the irradiated kidney as compared to control rat kidneys （P 〈0.05）, and was most severe at the sixth and ninth month after irradiation （P 〈0.01）. By double immunostaining, CTGF expressing cells were found to be α-SMA-positive myofibroblasts and vimentin-positive tubular epithelial cells. Glomerular expression of CTGF closely correlated with the glomerular expression of a-SMA （r=0.628, P 〈0.01）, vimentin （r=0.462, P 〈0.05） and accumulation of type IV collagen （r=0.584, P 〈0.01） i