吡格列酮对糖尿病大鼠血清MMP-9水平及其外周血单核细胞中MMP-9表达的影响
《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]
- 期数:
- 2010年第1期
- 页码:
- 44-47
- 栏目:
- 基础研究
- 出版日期:
- 2010-01-04
文章信息/Info
- Title:
- Effect of pioglitazone on serum MMP-9 concentration and expression of peripheral monocyte MMP-9 in diabetic rats
- Author(s):
- CAO Yi; WANG Hao; TANG Hai-hong; GAO Lian-ru; FEI Yu-xing; ZHANG Ning-kun; YANG Ye; LI De-bin
- Department of Cardiology, Naval General Hospital, Beijing 100037, China
- Keywords:
- pioglitazone; diabetes; matrix metalloproteinase-9; rats
- 分类号:
- Q559
- DOI:
- -
- 文献标识码:
- A
- 摘要:
- 目的: 观察过氧化物酶体增殖物激活受体γ（PPARγ）配体吡格列酮对糖尿病大鼠血清基质金属蛋白酶9 (MMP-9) 浓度和外周血单核细胞中MMP-9表达的影响。方法: 40只Wistar大鼠随机分为5组，即对照组、糖尿病组和不同剂量5、10、20 mg/(kg·d)吡格列酮治疗组，每组8只。给糖尿病组和3个吡格列酮治疗组大鼠腹腔注射链脲霉素制作糖尿病大鼠模型后，各吡格列酮治疗组以不同剂量的吡格列酮灌胃：5、10、20 mg/(kg·d)，共28 d；对照组和糖尿病组以等量生理盐水灌胃。比较治疗前、后的血清MMP-9浓度的变化。分离大鼠外周血单核细胞，用RT-PCR和Western blot检测MMP-9表达的变化。结果: 与对照组比较，吡格列酮降低血清MMP-9的浓度(P<0.05)，降低外周血单核细胞中MMP-9的表达。结论: 吡格列酮可以降低糖尿病大鼠血清MMP-9浓度及外周血单核细胞中MMP-9的表达，提示其在降糖之外还具有心血管保护作用。
- Abstract:
- AIM: To observe the effect of pioglitazone on serum MMP-9 concentration and expression of peripheral monocyte MMP-9 in diabetic rats. METHODS: Forty Wistar rats were randomly divided into five groups: control group, diabetes group and three pioglitazone groups of 5, 10, 20 mg/(kg·d), respectively. The rat diabetic model was made by IP injection of streptozocin. After the model was successfully made, rats in pioglitazone group were treated with pioglitazone ［5, 10 or 20 mg/(kg·d)×28 days］JP by gavage and rats in the control group and diabetes group were treated with normal saline. Concentrations of serum MMP-9 were detected by ELISA. Expression of peripheral monocyte MMP-9 was measured by RT-PCR and Western blot. RESULTS: The concentration of serum MMP-9 was dose-dependently lowered by pioglitazone treatment. Expression of peripheral monocyte MMP-9 was also down-regulated by pioglitazone treatment. CONCLUSION: Results indicate that pioglitazone may have some protective cardiovascular effect in addition to a hypoglycemic effect.
参考文献/References
［1］ Marx N, Froehlich J, Siam L, et al. Antidiabetic PPAR gamma-activator rosiglitazone reduces MMP-9 serum levels in type 2 diabetic patients with coronary artery disease［J］. Arterioscler Thromb Vasc Biol, 2003, 23(2):283-288.
［2］ Uemura S, Matsushita H, Li W, et al. Diabetes mellitus enhances vascular matrix metalloproteinase activity: role of oxidative stress［J］. Circ Res, 2001, 88(12):1291-1298.
［3］ Rodríguez JA, Orbe J, Páramo JA. Metalloproteases, vascular remodeling and atherothrombotic syndromes［J］. Rev Esp Cardiol, 2007, 60(9):959-967.
［4］ Michalik L, Auwerx J, Berger JP, et al. International Union of Pharmacology. LXI. Peroxisome proliferator-activated receptors［J］. Pharmacol Rev, 2006, 58(4):726-741.
［5］ Kappert K, Meyborg H, Clemenz M, et al. Insulin facilitates monocyte migration: a possible link to tissue inflammation in insulin-resistance［J］. Biochem Biophys Res Commun, 2008, 365(3):503-508.
［6］ Beaudeux JL, Giral P, Bruckert E, et al. Matrix metalloproteinases and atherosclerosis. Therapeutic aspects［J］. Ann Biol Clin (Paris), 2003, 61(2):147-158.
［7］ Worley JR, Baugh MD, Hughes DA, et al. Metalloproteinase expression in PMA-stimulated THP-1 cells. Effects of peroxisome proliferator-activated receptor-gamma (PPAR gamma) agonists and 9-cis-retinoic acid［J］. J Biol Chem, 2003, 278(51): 51340-51346.
备注/Memo
- 备注/Memo:
- 收稿日期：2009-2-12.通讯作者：王浩，主治医师，主要从事心血管内科临床与基础研究Email:wanghao2003@sina.com 作者简介：曹毅，主治医师，硕士Email：caoyi76@163.com
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