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糖尿病中的主动脉僵硬度——与谷氨酰胺和热休克蛋白70表达的关联:基于实验性啮齿动物模型的初步研究

Aortic stiffness in diabetes mellitus--association with glutamine and heat shock protein 70 expression: a pilot study based on an experimental rodent model.

作者信息

Ugurlucan Murat, Erer Dilek, Kalko Yusuf, Gungor Funda, Haholu Aptullah, Basaran Murat, Banach Maciej, Rysz Jacek, Mikhailidis Dimitri P, Tireli Emin, Dayioglu Enver, Alpagut Ufuk

机构信息

Istanbul University Istanbul Medical Faculty, Department of Cardiovascular Surgery, Atasehir, Zumrut Sitesi, Blok: 9, Daire: 9, 81120 Atasehir/Istanbul, Turkey.

出版信息

Expert Opin Ther Targets. 2009 Mar;13(3):267-74. doi: 10.1517/14728220902735833.

DOI:10.1517/14728220902735833
PMID:19236149
Abstract

BACKGROUND

Diabetes mellitus (DM) alters arterial wall compliance and causes aortic stiffness, which is a predictor of vascular mortality. Heat shock proteins (HSPs) are involved in the protection of cells under stress. We evaluated aortic stiffness in DM and the effects of glutamine (which induces HSP 70) on HSP 70 levels in experimental DM.

MATERIALS AND METHODS

Male Sprague-Dawley rats (n = 30) were divided into three groups: Control (Group 1), DM (Group 2) and glutamine-treated DM (Group 3). DM was induced using streptozocin injection. Group 3 rats received two doses of glutamine during the fourth week. Blood and infrarenal aortic tissue samples were obtained for analysis at the end of the fourth week.

RESULTS

Compared with Group 1, serum HSP 70 levels were significantly increased in Groups 2 and 3. Aortic HSP 70 was increased in DM. There was a significant difference in aortic HSP 70 with glutamine injection (Group 1 versus Group 3). DM also interfered with the elastin content of the aorta. There was a significant correlation between the serum glucose and serum and aortic HSP 70 levels and between serum and aortic HSP 70 levels; as well as between severity of DM and aortic elastin levels.

CONCLUSIONS

DM causes aortic stiffness and this may contribute to the increase in mortality and morbidity associated with DM. The expression of HSP 70 may become a therapeutic target.

摘要

背景

糖尿病(DM)会改变动脉壁顺应性并导致主动脉僵硬,而主动脉僵硬是血管死亡率的一个预测指标。热休克蛋白(HSPs)参与在应激状态下对细胞的保护。我们评估了糖尿病状态下的主动脉僵硬情况以及谷氨酰胺(可诱导HSP 70)对实验性糖尿病中HSP 70水平的影响。

材料与方法

将30只雄性Sprague-Dawley大鼠分为三组:对照组(第1组)、糖尿病组(第2组)和谷氨酰胺治疗的糖尿病组(第3组)。通过注射链脲佐菌素诱导糖尿病。第3组大鼠在第四周接受两剂谷氨酰胺。在第四周结束时获取血液和肾下腹主动脉组织样本进行分析。

结果

与第1组相比,第2组和第3组血清HSP 70水平显著升高。糖尿病组主动脉HSP 70增加。注射谷氨酰胺后主动脉HSP 70有显著差异(第1组与第3组)。糖尿病还干扰了主动脉的弹性蛋白含量。血清葡萄糖与血清及主动脉HSP 70水平之间、血清与主动脉HSP 70水平之间;以及糖尿病严重程度与主动脉弹性蛋白水平之间存在显著相关性。

结论

糖尿病导致主动脉僵硬,这可能导致与糖尿病相关的死亡率和发病率增加。HSP 70的表达可能成为一个治疗靶点。

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