中晚期糖尿病肾病患者交感神经兴奋性与肾脏纤维化血清指标TGF-β1、MMP-2水平的相关性分析

Correlation between Sympathetic Nerve Excitability and Serum TGF-β1, MMP-2 and VEGF in patients with Advanced Diabetic Nephropathy

目的:回顾性分析中晚期糖尿病肾病(DN,MogensonⅢ至Ⅴ期)患者交感神经兴奋性与肾纤维化指标的相关性。方法:DN患者86例(DN组,其中Ⅲ期组26例,Ⅳ期组32例,Ⅴ期组28例),2型糖尿病(T2DM)患者30例作为对照组。收集各组患者血压(SBP)、心率(HR)、血红蛋白(Hb)、肾小球滤过率(GFR)、24h尿蛋白(24hUpro)等病例资料;采用ELISA法测定纤维化指标:转化生长因子β1(TGF-β1)和金属基质蛋白酶-2(MMP-2)血清水平,采用高效液相色谱法检测交感神经兴奋性指标:去甲肾上腺素(NE)浓度。比较各组SBP、HR、HB、GFR、24hUpro、TGF-β1、MMP-2、NE水平差异,分析DN患者血清NE水平与TGF-β1、MMP-2水平的相关性。结果:DNⅤ期患者SBP、HR显著高于对照组(P<0.05),DNⅣ期、Ⅴ期患者GFR较对照组明显下降(均P<0.05);DNⅢ-V期患者NE水平明显高于对照组(均P<0.05),DNⅣ期、Ⅴ期患者MMP-2、TGF-β1水平高于对照组(均P<0.05),DN患者血清NE水平与MMP-2、TGF-β1均呈正相关(r=0.962、0.920,均P<0.01)。结论:DN患者交感神经兴奋性和肾脏纤维化在其晚期表现明显,尤以交感神经兴奋性升高出现更早,提示交感神经过度兴奋可能参与了DN患者肾脏纤维化、肾功能衰竭的病变过程。

Objective:To retrospectively analyze the correlation between sympathetic excitability and renal fibrosis in patients with advanced diabetic nephropathy(DN,Mogenson III-V).Method:86 patients with DN(26 in stage III,32 in stage IV and 28 in stage V)and 30 patients with type 2 diabetes mellitus(T2DM)were selected as control group.The blood pressure(SBP),heart rate(HR),glomerular filtration rate(GFR),24-hour urinary protein(24h Upro)and other case data of each group were collected.The serum levels of transforming growth factor-β1(TGF-β1)and metal matrix protease-2(MMP-2)were measured by ELISA,and the sympathetic excitability index and norepinephrine(NE)was detected by high performance liquid chromatography.The levels of SBP,HR,HB,24h Upro,GFR,TGF-β1,MMP-2 and NE in each group were compared,and the correlation between serum NE level and TGF-β1,MMP-2 in DN patients was analyzed.Results:SBP and HR in patients with stage V DN were significantly higher than those in the control group(P<0.05),GFR in patients with stage IV and V DN was significantly lower than those in the control group(P<0.05),NE expression in patients with stage III-V DN was significantly higher than that in the control group(P<0.05),MMP-2 and TGF-β1 levels in patients with stage IV and V DN were higher than those in the control group(P<0.05),NE level and serum MMP-2 and TGF-β1 levels in patients with DN were all higher than those in the control group There was a positive correlation(r=0.962,r=0.920,all P<0.01).Conclusion:Sympathetic excitability and renal fibrosis in DN patients are obvious in the late stage,especially in the early stage of the increase of sympathetic excitability,suggesting that sympathetic overexcitation may be involved in the pathological process of renal fibrosis and renal failure in DN patients.