C-反应蛋白对慢性肾脏病肾功能的影响及其机制的探讨

Effects of C-reactive protein on renal function of chronic kidney disease and its mechanism

目的:探讨C-反应蛋白(CRP)在慢性肾脏病(CKD)进展中的作用。方法:测定56例非透析CKD患者血CRP及肾功能指标,分析它们之间的相关性。并在体外观察CRP刺激人近端肾小管上皮细胞分泌转化生长因子-β1(TGF-β1)以及细胞外基质Ⅰ型胶原蛋白(ColⅠ)、Ⅳ型胶原蛋白(ColⅣ)的水平。结果:血循环CRP随肾功能减退而增高(P<0.001),CRP与肾小球滤过率呈负相关(r=-0.648,P<0.001)。在体外培养中,与对照组相比,细胞培养上清液TGF-β1、ColⅠ、ColⅣ呈时间依赖性(P<0.001)和剂量依赖性增加(P<0.001)。结论:循环中增高的CRP可能通过刺激肾小管上皮细胞细胞外基质合成分泌增多,促进CKD肾功能的恶化。

Objective To investigate the effect of C-reactive protein （CRP） on progression of chronic kidney disease （CKD）. Methods Serum level of CRP and renal function parameters were determined in 56 CKD patients without hemodialysis,and the correlations between them were analyzed. Also,in vitro experiments were conducted to observe the secretion of transforming growth factor β1 （TGF-β1） and extracellular matrix of collagen Ⅰ （Col Ⅰ） and collagen Ⅳ （Col Ⅳ） in cultured human proximal tubular epithelium cell line HK-2 induced by CRP. Results The serum level of CRP was increased with the worsening of renal function,and was negatively correlated with glomerular filtration rate （r = -0.648,P 0.001）. Stimulated by CRP in vitro,the levels of TGF-β1,Col Ⅰ,and Col Ⅳ in the supernatant of HK-2 cells were increased in a dose-and time-dependent manner in comparison with control group （P 0.001）. Conclusion Elevated CRP may contribute to the progression of CKD through stimulating the synthesis and secretion of extracellular matrix by renal tubular epithelial cells.