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[尿结缔组织生长因子作为大鼠模型中慢性移植肾肾病的生物标志物]

[Urinary connective tissue growth factor as a biomarker chronic allograft nephropathy in a rat model].

作者信息

Luo Guang-heng, Sun Zhao-lin, Xia Shu-jie

机构信息

Department of Urology, Guizhou Province People's Hospital, Guiyang 550002, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2010 Jul 27;90(28):1999-2003.

Abstract

OBJECTIVE

To determine whether urinary connective tissue growth factor (CTGF) can be a molecular marker for chronic allograft nephropathy (CAN) in a rat model.

METHODS

F344 rat renal grafts were orthotopically transplanted into Lewis rats (n = 24). Lewis rats underwent sham operation as control group (n = 12). Kidney grafts were harvested at Weeks 4, 8, 12 and 16 respectively. Serum creatinine (SCr) was measured. The CAN grades were evaluated according to the Banff 97 schema. The expressions of CTGF in kidney, serum and urine were determined by Western blot and competitive indirect ELISA. Spearman correlation analysis was used to compare CTGF expression and the development of CAN.

RESULTS

The expression of CTGF in the graft group was markedly elevated in comparison with the control group. Statistics analysis of CTGF protein in kidney detected by Western blot showed significant differences between these five groups (0.33 ± 0.05 for control, 0.55 ± 0.02 for Week 4, 0.80 ± 0.03 for Week 8, 0.90 ± 0.03 for Week 12 and 1.14 ± 0.11 for Week 16, P < 0.01). Both urine and serum CTGF increased by Week 4 and maintained a high level up to Week 16. The urinary CTGF of renal allografts was (2.9 ± 0.7), (12.9 ± 3.6), (32.3 ± 11.4) and (31.0 ± 8.9) ng/mg creatinine for Weeks 4, 8, 12 and 16 respectively. The urinary levels were positively correlated with SCr, Banff scores and expression of CTGF in the graft kidney (r = 0.848, 0.874, 0.747, all P < 0.01).

CONCLUSIONS

CTGF plays a significant role in the pathological changes of CAN after kidney transplantation. Urinary CTGF has the potential as a biomarker for predicting the clinical course of CAN.

摘要

目的

在大鼠模型中确定尿结缔组织生长因子(CTGF)是否可作为慢性移植肾肾病(CAN)的分子标志物。

方法

将F344大鼠肾移植到Lewis大鼠体内(n = 24)。Lewis大鼠接受假手术作为对照组(n = 12)。分别在第4、8、12和16周采集肾移植组织。检测血清肌酐(SCr)。根据Banff 97标准评估CAN分级。采用蛋白质免疫印迹法和竞争性间接酶联免疫吸附测定法测定肾组织、血清和尿液中CTGF的表达。采用Spearman相关分析比较CTGF表达与CAN进展情况。

结果

与对照组相比,移植组CTGF表达明显升高。蛋白质免疫印迹法检测肾组织中CTGF蛋白的统计学分析显示,这五组之间存在显著差异(对照组为0.33±0.05,第4周为0.55±0.02,第8周为0.80±0.03,第12周为0.90±0.03,第16周为1.14±0.11,P < 0.01)。尿液和血清CTGF在第4周时均升高,并在第16周前维持在较高水平。肾移植术后第4、8、12和16周尿CTGF水平分别为(2.9±0.7)、(12.9±3.6)、(32.3±11.4)和(31.0±8.9)ng/mg肌酐。尿CTGF水平与SCr、Banff评分及移植肾中CTGF表达呈正相关(r = 0.848、0.874、0.747,均P < 0.01)。

结论

CTGF在肾移植后CAN的病理变化中起重要作用。尿CTGF有潜力作为预测CAN临床病程的生物标志物。

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