羟苯磺酸钙对糖尿病大鼠主动脉的保护作用

山东大学学报(医学版) ›› 2010, Vol. 48 ›› Issue (10): 4-.

羟苯磺酸钙对糖尿病大鼠主动脉的保护作用

孔德焕1，于进堂2，高美娟1，李波1，卞丽香1，李明龙3，刘明4，于桂娜1

1.山东大学附属省立医院内分泌科，山东省临床医学研究院内分泌代谢研究所，济南 250021；
2.青岛大学医学院附属医院海阳分院, 山东海阳 265100; 3.山东大学附属省立医院保健科, 济南 250021；
4.山东大学附属省立医院核医学科, 济南 250021

收稿日期:2010-06-01 出版日期:2010-10-16 发布日期:2010-10-16
通讯作者: 于桂娜（1955- ），女，主任医师，研究方向为内分泌与代谢病。E-mail: yugn@163.com
作者简介:孔德焕（1977- ），女，硕士研究生，主要研究方向为糖尿病及其并发症。

Protection of calcium dobesilate on the aorta of diabetic rats

KONG De-huan1, YU Jin-tang2, GAO Mei-juan1, LI Bo1, BIAN Li-xiang1, LI Ming-long3, LIU Ming4, YU Gui-na1

1. Department of Endocrinology, Provincial Hospital Affiliated to Shandong University, Institute of Endocrinology and
Metabolism of Clinical Research Institute of Shandong Province, Jinan 250021, China;
2. Haiyang Hospital Affiliated to School of Medicine of Qingdao University, Haiyang 265100, Shandong, China;
3. Department of Nuclear Medicine, Provincial Hospital Affiliated to Shandong University, Jinan 250021, China;
4. Department of Healthy Care, Provincial Hospital Affiliated to Shandong University, Jinan 250021, China

Received:2010-06-01 Online:2010-10-16 Published:2010-10-16

摘要/Abstract

摘要：

目的用腹腔注射链脲佐菌素（STZ）的方法制备大鼠糖尿病模型，通过检测糖尿病大鼠主动脉中纤溶酶原激活物抑制物-1（PAI-1）及基质金属蛋白酶-9（MMP-9）的表达和血浆中PAI-1及内皮素（ET）含量的改变，观察羟苯磺酸钙对糖尿病大鼠主动脉的保护作用并探讨其机制。方法用STZ建立大鼠糖尿病（DM）模型,将DM模型大鼠随机分为羟苯磺酸钙组和糖尿病组，并设正常对照组，每组10只。羟苯磺酸钙组每天给予羟苯磺酸钙0.15mg/g灌胃，其余两组给予相同剂量的蒸馏水。各组大鼠分别干预8周。处死前抽血备测血清学指标，处死后固定主动脉留做形态学观察。分别用放射免疫法和酶联免疫吸附法（ELISA）测定血浆中ET和PAI-1含量。用免疫组化技术检测大鼠主动脉PAI-1、MMP-9的表达，光镜、电镜下观察主动脉病理形态的改变。结果与糖尿病组相比，羟苯磺酸钙能降低血浆ET和PAI1的含量（P<0.05），改善大鼠主动脉病理损伤，减少主动脉局部PAI1和MMP9的表达（P<0.05）。糖尿病组大鼠主动脉内膜增厚,内皮细胞肿胀,平滑肌细胞增生、排列紊乱。羟苯磺酸钙组大鼠主动脉上述病变明显减轻。结论羟苯磺酸钙能显著降低糖尿病大鼠ET、PAI-1和MMP-9的表达量，抑制血小板聚集 ,降低血管通透性，保护血管内皮，延缓动脉硬化，稳定粥样斑块。

关键词: 羟苯磺酸钙；糖尿病；模型，动物；主动脉；纤溶酶原激活剂抑制物1；基质金属蛋白酶9；内皮素；大鼠，Wistar

Abstract:

Objective To investigate the effect of calcium dobesilate on the aorta of diabetic rats and explore its possible mechanism. Methods The Diabetes mellitus(DM) model was established by a single injection of streptozotocin(STZ)and DM rats were randomly divided into the calcium dobsilate group and the diabetic group. Normal rats served as the normal group. Each group contained 10 rats. In the calcium dobsilate group, rats were treated intragastrically with 0.15mg/g calcium dobsilate every day while the same dose of distilled-water was applied in the other groups. The treatment lasted for 8 weeks. Before being sacrificed, blood samples were drawn to measure serum indicators. After being sacrificed, the aorta was fixed to observe morphological changes. Plasma endothelin (ET) and Plasminogen activator inhibitor-1(PAI-1) levels were measured respectively with radioimmunoassay and enzyme linked immunosorbent assay (ELISA). Expression of PAI-1 and matrix metalloprotein-9(MMP-9)in the aorta were determined with immunohistological chemistry. Results Compared with the diabetic group, the plasma level of ET and PAI-1 were decreased(P<0.05) by calcium dobesilate. Expression of PAI-1 and MMP-9 in the aorta was decreased by calcium dobesilate. Rats in the DM group showed abnormal aortic ultra-structure, including incrassated intima, varicose endothelial cells, proliferation and disorder of smooth muscle cells. These phenomena were significantly alleviated in the calcium dobesilate group. Conclusion Calcium dobesite can protect blood vessel endothelium, inhibit platelet aggregation, delay arteriosclerosis, stabilize atheromatous plaque via down-regulation of ET and PAI-1 in plasma and inhibition of PAI-1 and MMP-9 expression in the aorta.

Key words: Calcium dobesilate; Animal model; Diabetic mellitus; Aorta; Plasminogen activator inhibitor-1; Matrix metalloprotein-9; Endothelin; Wistar rats

中图分类号:

R587.2

孔德焕1，于进堂2，高美娟1，李波1，卞丽香1，李明龙3，刘明4，于桂娜1. 羟苯磺酸钙对糖尿病大鼠主动脉的保护作用[J]. 山东大学学报(医学版), 2010, 48(10): 4-.

KONG De-huan1, YU Jin-tang2, GAO Mei-juan1, LI Bo1, BIAN Li-xiang1, LI Ming-long3, LIU Ming4, YU Gui-na1. Protection of calcium dobesilate on the aorta of diabetic rats[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2010, 48(10): 4-.

参考文献

相关文章 11

[1]	毕大鹏1，嵇高德1，张洪星2 . 通心络胶囊对早期糖尿病肾病患者胱抑素C的影响[J]. 山东大学学报(医学版), 2013, 51(7): 67-69.
[2]	周雁1,郭立新1,周璐2，汪耀1，牟忠卿1，王晓霞1，于冬妮1，张丽娜11,周璐2，汪耀1，牟忠卿1，王晓霞1，于冬妮1，张丽娜1. 老年2型糖尿病患者周围神经病变的影响因素[J]. 山东大学学报(医学版), 2012, 50(6): 1-4.
[3]	王倩1,张莹1,侯为开1,张莉2,徐华3,王鹏4,于珊1, 刘骞1,黄庆先1. 2型糖尿病性腹泻与肠神经系统病变关系的探讨[J]. 山东大学学报(医学版), 2011, 49(8): 13-.
[4]	侯亮，刘雪平，袁树华，王美霞，徐松. 胰岛素抵抗大鼠血管AGEs水平及其损伤机制和吡格列酮的保护作用[J]. 山东大学学报(医学版), 2010, 48(4): 5-9.
[5]	张月华，赵新国，岳玉国，吕英俊. 诺和锐30特充强化治疗初诊2型糖尿病疗效观察[J]. 山东大学学报(医学版), 2010, 48(4): 160-.
[6]	李文斌1，崔美玉1，许冬梅1，关广聚2. 二基肽酶IV酶活性与糖尿病肾病的相关性[J]. 山东大学学报(医学版), 2010, 48(3): 12-14.
[7]	李倩，汪翼，孙书珍，陈瑶，王立俊. 糖尿病大鼠心肌胶原代谢的变化及与MMP-2/TIMP-2表达的关系[J]. 山东大学学报(医学版), 2010, 48(3): 1-6.
[8]	. 2，5二羟苯磺酸钙对糖尿病大鼠心肌保护作用的研究[J]. 山东大学学报(医学版), 2009, 47(10): 9-14.
[9]	李宪花高海青李保应程梅许玲胡昭. 葡萄子原花青素对糖尿病肾病大鼠非酶糖基化终产物和骨形态蛋白7表达的影响[J]. 山东大学学报(医学版), 2009, 47(5): 16-22.
[10]	孙洁任建民陈超刘昌盛司庆盈. 糖尿病合并冠心病与白蛋白尿的相关性研究[J]. 山东大学学报(医学版), 2009, 47(5): 102-105.
[11]	. 下肢动脉病变评分与糖尿病足1年截肢率的相关性研究[J]. 山东大学学报(医学版), 2009, 47(8): 10-13.

多维度评价

Viewed

Full text

Abstract

Cited

Shared

Discussed