在生理老化过程中和在糖尿病小鼠模型中动脉壁的结构改变：这些变化是否具有可比性？

Structural modifications in the arterial wall during physiological aging and as a result of diabetes mellitus in a mouse model: are the changes comparable?

机构信息

Laboratory for the Biology of Vascular Aging, School of Medicine, University Hospital of Lille, Lille, France.

出版信息

Diabetes Metab. 2011 Apr;37(2):106-11. doi: 10.1016/j.diabet.2010.08.005. Epub 2010 Dec 7.

DOI:10.1016/j.diabet.2010.08.005

PMID:21144786

Abstract

AIM

Vascular accelerated aging represents the major cause of morbidity and mortality in subjects with diabetes mellitus. In the present study, our aim was to compare premature functional and morphological changes in the arterial wall resulting from streptozotocin (STZ)-induced diabetes mellitus in mice over a short-term period with those that develop during physiological aging. The effect of aminoguanidine (AG) on the prevention of these alterations in the diabetic group was also analyzed.

METHODS

The vascular relaxation response to acetylcholine (ACh) in the mouse was tested in isolated segments of phenylephrine (Phe)-precontracted aorta at 2, 4 and 8 weeks (wk) of STZ-induced diabetes and compare to 12- and 84-wk-old mice. Aortic structural changes were investigated, and receptor for AGE (RAGE) aortic expression was quantified by western blot.

RESULTS

Compared to the 12-wk control group (76 ± 5%), significant endothelium-dependant relaxation (EDR) impairment was found in the group of 12-wk-old mice, which underwent a 4-wk diabetes-inducing STZ treatment (12wk-4WD) (52 ± 4%; P < 0.01) and was yet more apparent in the group of 16-wk-old mice, which underwent an 8-wk diabetes-inducing STZ treatment (16wk-8WD) (34 ± 4%; P < 0.001). The alteration in EDR was relatively comparable between the diabetic 12wk-4WD group and the 84-wk-old group (52.7 ± 4 vs. 48 ± 4%). Intima/media aortic thickening and aortic structural changes were significantly increased in the diabetic 12wk-4WD group and were even more apparent in the 84-wk group compared to the 12-wk controls. AG treatment in the 12wk-4WD+AG diabetic group significantly improved EDR, decreased RAGE expression and showed an aging preventive effect on the structural changes of the arterial wall.

CONCLUSION

Our study compared EDR linked to physiological aging with that observed in the case of STZ-induced diabetes over a short-term period, and demonstrated the beneficial effect of AG.

摘要

目的

血管加速老化是导致糖尿病患者发病率和死亡率的主要原因。本研究旨在比较短期链脲佐菌素（STZ）诱导的糖尿病小鼠动脉壁过早的功能和形态变化与生理衰老过程中发生的变化。还分析了氨基胍（AG）对预防糖尿病组这些改变的影响。

方法

在 2、4 和 8 周（wk）STZ 诱导的糖尿病小鼠分离的苯肾上腺素（Phe）预收缩主动脉段中测试乙酰胆碱（ACh）的血管舒张反应，并与 12 和 84 周龄小鼠进行比较。研究了主动脉结构变化，并通过 Western blot 定量了 AGE 受体（RAGE）主动脉表达。

结果

与 12 周龄对照组（76±5%）相比，接受 4 周糖尿病诱导 STZ 治疗的 12 周龄小鼠（12wk-4WD）的内皮依赖性舒张（EDR）明显受损（52±4%；P<0.01），而接受 8 周糖尿病诱导 STZ 治疗的 16 周龄小鼠（16wk-8WD）更为明显（34±4%；P<0.001）。EDR 的改变在糖尿病 12wk-4WD 组和 84 周龄组之间相对可比（52.7±4%比 48±4%）。糖尿病 12wk-4WD 组的主动脉内-中膜厚度和主动脉结构变化明显增加，而与 12 周龄对照组相比，84 周龄组更为明显。糖尿病 12wk-4WD+AG 组的 AG 治疗显著改善 EDR，降低 RAGE 表达，并对动脉壁结构变化表现出抗衰老作用。