Onuta Geanina, Groenewegen Hendrik C, Klatter Flip A, Walther Boer Mark, Goris Maaike, van Goor Harry, Roks Anton J M, Rozing Jan, de Smet Bart J G L, Hillebrands Jan-Luuk
Section of Immunology, Department of Cell Biology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
J Biomed Biotechnol. 2011;2011:396734. doi: 10.1155/2011/396734. Epub 2011 Feb 9.
Type 1 diabetic patients have increased risk of developing in-stent restenosis following endovascular stenting. Underlying pathogenetic mechanisms are not fully understood partly due to the lack of a relevant animal model to study the effect(s) of long-term autoimmune diabetes on development of in-stent restenosis. We here describe the development of in-stent restenosis in long-term (~7 months) spontaneously diabetic and age-matched, thymectomized, nondiabetic Diabetes Prone BioBreeding (BBDP) rats (n = 6-7 in each group). Diabetes was suboptimally treated with insulin and was characterized by significant hyperglycaemia, polyuria, proteinuria, and increased HbA(1c) levels. Stented abdominal aortas were harvested 28 days after stenting. Computerized morphometric analysis revealed significantly increased neointima formation in long-term diabetic rats compared with nondiabetic controls. In conclusion, long-term autoimmune diabetes in BBDP rats enhances in-stent restenosis. This model can be used to study the underlying pathogenetic mechanisms of diabetes-enhanced in-stent restenosis as well as to test new therapeutic modalities.
1型糖尿病患者在血管内支架置入术后发生支架内再狭窄的风险增加。部分由于缺乏相关动物模型来研究长期自身免疫性糖尿病对支架内再狭窄发生的影响，其潜在发病机制尚未完全明确。我们在此描述了长期（约7个月）自发性糖尿病且年龄匹配、胸腺切除的非糖尿病易患糖尿病生物繁殖（BBDP）大鼠（每组6 - 7只）支架内再狭窄的发生情况。糖尿病采用胰岛素进行次优治疗，其特征为显著高血糖、多尿、蛋白尿以及糖化血红蛋白（HbA1c）水平升高。支架置入28天后摘取置入支架的腹主动脉。计算机形态计量分析显示，与非糖尿病对照组相比，长期糖尿病大鼠的新生内膜形成显著增加。总之，BBDP大鼠的长期自身免疫性糖尿病会加重支架内再狭窄。该模型可用于研究糖尿病加重支架内再狭窄的潜在发病机制以及测试新的治疗方法。
