多贝斯联合贝纳普利治疗对早期糖尿病肾病患者肾损伤的保护作用及可能分子机制探究

Protective effect of calcium dobesilate combined with benazepril therapy on renal injury in patients with early diabetic nephropathy and the possible molecular mechanisms

目的:探讨多贝斯联合贝纳普利治疗对早期糖尿病肾病患者肾损伤的保护作用及可能分子机制。方法:收集在本院接受治疗的早期糖尿病肾病患者50例,随机分为观察组及对照组各25例。在常规治疗基础上,对照组加入贝纳普利治疗,观察组加入多贝斯联合贝纳普利治疗,持续3月。治疗前后,采用全自动生化分析仪检测外周血肾损伤指标含量,采用放射免疫法检测尿肾损伤指标含量;采用ELISA法检测肾纤维化指标含量;采用Western-blot法检测肾组织TGF-β1/BMP-7、Smad信号通路分子蛋白表达量。结果:治疗前,两组肾损伤指标含量、肾纤维化指标含量、信号通路分子蛋白表达量比较,差异无统计学意义(P>0.05)。治疗后,观察组外周血中BUN、SCr、β-TP及尿液中KIM-1含量低于对照组(P<0.05);观察组血清中肾纤维化指标标TGF-β1、CTGF、TIMP-1、LN、HA含量低于对照组(P<0.05);观察组肾组织中TGF-β1、Smad2/3蛋白表达量低于对照组,Smad7、BMP-7蛋白表达量高于对照组(P<0.05)。结论:多贝斯联合贝纳普利治疗可减轻早期糖尿病肾病患者的肾损伤、抑制纤维化进程,通过调控TGF-β1/BMP-7、Smad信号通路功能实现以上疗效。

Objective： To explore the protective effect of calcium dobesilate combined with benazepril therapy on renal injury in patients with early diabetic nephropathy and the possible molecular mechanisms. Methods： A total of 50 patients with early diabetic nephropathy treated in our hospital between May 2012 and January 2016 were collected, and according to the ran dom number table, the patients were divided into observation group （n = 25） and control group （n = 25）. On the basis of conventional treatment, control group of patients received benazepril therapy, observation group of patients received calcium dohesilate combined with benazepril therapy, and the treatment lasted for 3 months. Before and after treatment, automatic biochemical analyzer was used to detect the levels of renal injury indexes in peripheral blood, RIA method was used to detect the levels of renal injury indexes in urine, ELISA method was used to detect the levels of renal fibrosis indexes and Western-blot method was used to detect the protein expression of TGF-β1/BMP-7 and Smad signaling pathway molecules in renal tissue. Resuits.. Before treatment, differences in renal injury index levels, renal fibrosis index levels and signaling pathway molecule protein expression were not statistically significant between two groups of patients （P〉0.05）. After treatment, BUN, SCr and β- TP levels in the peripheral blood as well as KIM-1 level in urine of observation group were lower than those of control group （P 〈0.05）; renal fibrosis indexes TGF-β1, CTGF, TIMP-1, LN and HA levels in serum of observation group were lower than those of control group （P 〈0.05）; TGF-β1 and Smad2/3 protein expression in renal tissue of observation group were lower than those of control group while Smad7 and BMP-7 protein expression were higher than those of control group （P 〈0.05）. Oonclusion： Calcium dobesilate combined with benazepril therapy can reduce the renal injury and inhibit the fibrosis process in patients with early diabetic nephropathy, and it achieves the above effect by regulating the TGF β1/BMP-7 and Smad signaling pathway function.