中国血液净化

中国血液净化 ›› 2019, Vol. 18 ›› Issue (02): 98-103.doi: 10.3969/j.issn.1671-4091.2019.02.005

• 临床研究 • 上一篇    下一篇

羟苯磺酸钙改善糖尿病肾病的微炎症状态和内皮细胞功能

周懿君1,邵兴华1,李舒1,戚超君1,徐华2,倪兆慧1   

  1. 1. 上海交通大学医学院附属仁济医院肾脏科
    2. 上海交通大学医学院附属仁济医院内分泌科
  • 收稿日期:2018-08-06 修回日期:2018-11-01 出版日期:2019-02-12 发布日期:2019-01-25
  • 通讯作者: 倪兆慧 nizhaohui2012@126.com E-mail:zhouyijun326@126.com
  • 基金资助:

    国家自然科学基金(81770666),上海市卫计委中西医结合专项重点项目ZHYY-ZXYJHZX-1-02，
    上海市卫计委项目(20154Y0003)黄芪甲苷调控线粒体功能防治肾损伤的机制研究

Calcium dobesilate can alleviate diabetes-induced endothelial dysfunction and inflammation

  • Received:2018-08-06 Revised:2018-11-01 Online:2019-02-12 Published:2019-01-25

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摘要： 【摘要】目的  探讨羟苯磺酸钙(calcium dobesilate，CaD)对糖尿病肾病(diabetic kidney disease, DKD)导致的肾脏内皮功能紊乱和炎症的保护作用，及其对DKD 的疗效和安全性。方法  采用病例对照研究，观察DKD 组患者与糖尿病无蛋白尿患者以及健康人群间，内皮相关标志物和炎症相关标志物的区别。采用前瞻性平行对照研究，选取DKD 组患者，随机分为用药组(口服CaD，每次500mg，每天3次)、观察组，治疗3 个月。检测治疗前后血管内皮生长因子(vascular endothelial growth factor, VEGF)、内皮素-1(endothelin-1,ET-1)、内皮型一氧化氮合酶(endothelial nitric oxide synthase, eNOS)、一氧化氮(nitric oxide,NO)和单核细胞趋化蛋白-1(monocyte chemotactic protein 1,MCP-1)、细胞间细胞粘附分子-1(intercellular cell adhesion molecule-1,ICAM)、五聚素3(pentraxin3, PTX3)。观察各项指标变化。结果  DKD 组患者PTX3、MCP-1、ICAM、VEGF、ET-1 显著高于糖尿病无蛋白尿患者，与24h 尿微量白蛋白呈正相关(r 值分别为0.356，0.254，0.247，0.267，0.216；P 值分别为0.001，0.003，0.004，0.002，0.012)，NO 低于糖尿病无蛋白尿患者(P＜0.001)，与24h 尿微量白蛋白呈负相关(r=-0.229，P=0.027)。Logistic 回归分析显示PTX3、NO、HbAlc 是DKD 的影响因素(OR 值分别为2.761, 0.941, 3.304；95% CI 分别为1.358～5.615，0.905～0.979，1.228～8.884；P 值分别为0.017, 0.003, 0.019)。ROC 曲线显示，糖尿病患者PTX3、NO、糖化血红蛋白(blood hematoglobin Alc，HbAlc)水平对DKD 有预测作用。前瞻性研究中，DKD 组患者服用CaD3个月后，24h 尿微量白蛋白、24h 尿总蛋白显著下降(P 值分别为0.010，0.014)。此外，用药后，患者微炎症指标PTX3、MCP-1、hsCRP、ICAM，以及内皮损伤标志物VEGF、NO、ET-1 较前皆有显著改善(P 值分别为0.008, 0.009, 0.040, 0.013, 0.003, 0.001, 0.004)。结论CaD 可能通过改善DKD 组患者的微炎症状态和内皮功能来减少尿蛋白、保护肾脏。

关键词: 糖尿病肾病, 内皮功能紊乱, 微炎症, 羟苯磺酸钙

Abstract: 【Abstract】Objective The aim of the present study was to elucidate the protective effects of calcium dobesilate (CaD) against diabetes-induced endothelial dysfunction and inflammation as well as the safety and efficacy of CaD in the treatment of diabetic kidney disease (DKD). Methods This was a prospective and casecontrol study to observe the differences in endothelial and inflammation related markers among DKD patients, diabetic patients without proteinuria and healthy individuals. DKD patients were then randomly divided into the treatment group (CaD 500mg, 3 times daily) and the observation group. They were treated for 3 months. Endothelial function markers including vascular endothelial growth factor (VEGF), endothelin-1(ET-1), endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) and inflammation markers including monocyte chemotactic protein 1 (MCP-1), intercellular cell adhesion molecule-1 (ICAM) and pentraxin 3 (PTX3) were assayed. Results In the 100 DKD patients, PTX3, MCP-1, ICAM, VEGF and ET-1 were significantly higher than those in diabetic patients without proteinuria (P＜0.001) and were positively correlated with the microamount of albuminuria (r=0.356, 0.254, 0.247, 0.267, 0.216 respectively; P=0.001, 0.003, 0.004, 0.002 and 0.012 respectively). NO was significantly lower in DKD patients than in diabetic patients without proteinuria (P＜0.001) and was negatively correlated with the micro-amount of albuminuria (r=-0.229, P=0.027). Logis-tic regression analysis showed that PTX3 (OR=2.761, 95% CI: 1.358～5.615, P=0.017), NO (OR=0.941, 95% CI: 0.905～0.979, P=0.003) and HbAlc (OR=3.304, 95% CI: 1.228～8.884, P=0.019) were the influence factors
for DKD. ROC curve showed that PTX3, NO and HbAlc levels were the predictive markers for the presence of DKD in diabetic patients. In the prospectively study of DKD patients treated with CaD for 3 months, their 24 hours urinary albumin and 24 hours urinary protein decreased significantly (P=0.010 and 0.014 respectively) but their cystatin C based GFR did not change. In DKD patients after CaD treatment, inflammation markers of PTX3, MCP-1, hsCRP and ICAM and endothelial markers of VEGF, NO and ET-1 ameliorated significantly as compared with those before CaD treatment (P=0.008, 0.009, 0.040, 0.013, 0.003, 0.001 and 0.004 respectively). Conclusion CaD can improve renal function in DKD patients through the improvement of their micro-inflammation status and endothelial function to reduce proteinuria.

Key words: diabetic kidney disease, endothelial dysfunction, inflammation, Calcium dobesilate