血清TGF-β_1、MMP-9/TIMP-1在不同分期慢性肾衰竭患者的表达

Expression of TGF-β_1,MMP-9/TIMP-1 in serum of patients with chronic renal failure at different stages

目的探讨慢性肾衰竭(CRF)患者不同分期血清转化生长因子-β1(TGF-β1)、基质金属蛋白酶-9(MMP-9)及金属蛋白酶组织抑制因子-1(TIMP-1)表达状况及其与肾脏纤维化的关系。方法60例CRF患者按估计肾小球滤过率(eG-FR)的不同被分为:第3期10例(eGFR30-59ml/min),第4期21例(eGFR15-29ml/min),第5期29例(eGFR<15ml/min),采用ELISA法检测不同分期的CRF患者和20例正常对照组血清TGF-β1、MMP-9及TIMP-1水平,分析这些指标与肾功能之间的相关性。结果TGF-β1在CRF组与对照组并没有统计学差异。MMP-9、TIMP-1在CRF组明显升高,MMP-9/TIMP-1比值则明显降低。随着eGFR的下降,MMP-9、TIMP-1呈同向性降低,而MMP-9/TIMP-1比值却逐渐升高。相关性分析显示,TIMP-1与血清肌酐(SCr)、eGFR分别呈负相关和正相关(r=-0.625,0.638,均P<0.001);MMP-9/TIMP-1比值与SCr、eGFR分别呈正相关和负相关(r=0.505,-0.516,均P<0.001)。结论血清MMP-9、TIMP-1参与了CRF的进展,血清TIMP-1水平或MMP-9/TIMP-1比值能较好地反映肾脏纤维化的程度。

Objective To investigate the serum expression of transforming growth factor β1 （ TGF-β1 ）, metalloproteinase matrix-9 （ MMP-9 ） and tissue inhibitor of metalloproteinase-1 （ TIMP-1 ） in patients with chronic renal failure（CRF） at different stages, and to explore their relations with the renal fibrosis. Methods Sixty CRF patients were divided into 3 groups according to estimated glomerular filtration rate （eGFR） ：10 patients with eGFR 30 -59 ml/min,21 patients with eGFR 15 -29 ml/min,29 patients with eGFR 〈 15 ml/ min. Serum levels of TGF-β1 ,MMP-9 and TIMP-1 were measured in CRF patients and 21 normal controls by ELISA. Their correlations with indices of renal function were analyzed. Results There was no significant difference in TGF-β1 between CRF patients and normal controls. Compared with normal controIs,the serum levels of MMP-9 and TIMP-1 significantly increased in CRF patients,while the ratio of MMP-9/TIMP-1 decreased. Serum MMP-9 and TIMP-1 levels decreased with the decrease of eGFR,while the ratio of MMP-9/ TIMP-1 increased. The serum levels of TIMP-1 showed a significantly negative and positive correlation with serum creatinine（ Scr）, eGFR,respectively（ r = -0. 625,0.638, P 〈 0.001 ）. While the ratio of MMP-9/TIMP-1 showed a significantly positive and negative correlation with Scr, eGFR（ r =0. 505, -0. 516 ,P 〈 0. 001 ）. Conclusion Serum MMP-9 and TIMP-1 may be involved in the progression of CRF. The serum levels of TIMP-1 or the ratio of MMP-9/TIMP-1 could preferably reflect the severity of renal fibrosis.