Sun Bin, Xing Chang-ying, He Wei-chun, Wang Ning-ning, Yu Xiang-bao, Zhao Xiu-fen, Qian Jun, Yang Jun-wei, Liu Jia, Wang Xiao-yun
Department of Nephrology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Zhonghua Yi Xue Za Zhi. 2007 Feb 27;87(8):562-6.
Is a common feature of progressive renal diseases regardless of the initiating insult To clarify the role of connective tissue growth factor (CTGF) in after (UUO) in renal interstitial fibrosis and effects of rapamycin (RAP) thereupon.
Eighteen Sprague-Dawley rats were randomly divided into 3 equal groups: unilateral ureteral obstruction (UUO) model group, undergoing ligation of the left ureter; RAP treatment group, undergoing ligation of the left ureter and intraperitoneal injection of RAP 0.04 mg.kg(-1).d(-1); and sham operation group. The right kidneys were taken out 7 and 14 days after the operation respectively to undergo renal pathological examination by Masson staining. Semi-quantitative RT-PCR was used to detect the mRNA expression of CTGF. Western blotting was performed to examine the protein expression of CTGF and fibronectin (FN).
In comparison with the sham operation group, renal interstitial fibrosis was significant more expression in the 2 UUO groups, especially the UUO model group (P < 0.01). Seven and 14 days after the operation the levels of CTGF mRNA expression of the UUO model and RAP treatment groups (both P < 0.01), and the level of CTGF mRNA expression of the RAP treatment group was significantly lower than that of the UUO model group (P < 0.01), however, there was no significant difference in the level of CTGF mRNA expression between the 2 UUO groups 14 days after the operation. Seven and 14 days after the operation the levels of CTGF protein expression of the UUO model and RAP treatment groups were both significantly higher than that of the sham operation group (both P < 0.01), and the levels of CTGF protein expression of the RAP treatment group were significantly lower than that of the UUO model group (P < 0.05 and P < 0.01). The levels of FN expression 7 and 14 days after the operation of the 2 UUO groups were both significantly higher than that of the sham operation group (both P < 0.01). and the level of FN expression 7 days after of the RAP treatment group was significantly lower than that of the UUO model group (P < 0.01), however, there was no significant difference in the level of FN expression between the 2 UUO groups 14 days after the operation.
The expression of CTGF mRNA and that of CTGF protein increase after UUO. Rapamycin play a protective role in the kidney by downregulating the CTGF expression and alleviating the renal interstitial fibrosis following UUO.
是进行性肾脏疾病的一个共同特征,无论起始损伤因素是什么 为阐明结缔组织生长因子(CTGF)在单侧输尿管梗阻(UUO)后肾间质纤维化中的作用及雷帕霉素(RAP)对此的影响。
18只Sprague-Dawley大鼠随机分为3组,每组6只:单侧输尿管梗阻(UUO)模型组,行左输尿管结扎术;RAP治疗组,行左输尿管结扎术并腹腔注射RAP 0.04mg·kg⁻¹·d⁻¹;假手术组。分别于术后7天和14天取出右肾,行Masson染色进行肾脏病理检查。采用半定量RT-PCR检测CTGF的mRNA表达。采用蛋白质印迹法检测CTGF和纤连蛋白(FN)的蛋白表达。
与假手术组相比,2个UUO组肾间质纤维化均更明显,尤其是UUO模型组(P<0.01)。术后7天和14天,UUO模型组和RAP治疗组CTGF mRNA表达水平均升高(均P<0.01),且RAP治疗组CTGF mRNA表达水平显著低于UUO模型组(P<0.01),但术后14天2个UUO组CTGF mRNA表达水平差异无统计学意义。术后7天和14天,UUO模型组和RAP治疗组CTGF蛋白表达水平均显著高于假手术组(均P<0.01),且RAP治疗组CTGF蛋白表达水平显著低于UUO模型组(P<0.05和P<0.01)。2个UUO组术后7天和14天FN表达水平均显著高于假手术组(均P<0.01),且RAP治疗组术后7天FN表达水平显著低于UUO模型组(P<0.01),但术后14天2个UUO组FN表达水平差异无统计学意义。
UUO后CTGF mRNA及CTGF蛋白表达增加。雷帕霉素通过下调CTGF表达、减轻UUO后的肾间质纤维化对肾脏起保护作用。