STZ诱导糖尿病大鼠心肌VEGF表达及血管密度变化对缺血再灌注损伤的影响

Effects of STZ-induced Diabetes on Ischemic/Reperfusion Injury of Rats Myocardium via Alterations in VEGF Expression and Angiogenesis

[目的]测定不同周期STZ诱导的糖尿病对心肌缺血/再灌注(I/R)损伤的影响及其与心肌VEGF表达及冠脉血管密度变化的关系。[方法]阻断和开放左冠状动脉前降支建立大鼠急性心肌I/R模型。分别用TTC染色、免疫印迹分析及Morphometric分析方法,测定大鼠心肌I/R后梗死面积、VEGF表达及冠脉血管密度。[结果]STZ处理后2周,糖尿病组(2WD)心肌梗死面积比相应周期对照组(2WC)明显缩小;STZ处理后16周(16WD),梗死面积比相应对照组(16WC)增加;Morphometric分析显示,心脏的冠脉血管密度在2WD组比2WC组显著增加(28%),而16WD组比16WC组明显减少(33%);血管内皮细胞生长因子(VEGF)的表达在2WD组比2WC组显著增加(30%),但在16WD组大鼠VEGF表达比16WC组明显减少。[结论]STZ诱导糖尿病早期、晚期对心肌I/R损伤呈现相反的作用。这可能是由于早、晚期糖尿病相反的心肌VEGF表达及冠脉血管密度改变而引起的。

[Objective] To determine the effects of different-term STZ-induced diabetes on ischemia/repeffusion （I/R） injury of myocardial and to determine whether I/R injury is related to diabetes-induced alterations in vascular endothelial growth factor （VEGF） expression and cardiac vascular density. [Methods] The models of I/R injury were induced by occlusion and reperfusion of the left descending coronary artery of rats. Size of I/R-induced infarct was determined using triphenyhetrazolium chloride （TIC） staining. VEGF expression was quantified by Western blot analysis. Cardiac vascular density was quantified by morphometric analysis. [Result] Two weeks after STZ treatment, infarct size was decreased in the 2 weeks diabetic hearts （2WI）） as compared with time-matched control group （2WC）. Whereas after 16 weeks of diabetes （16WD）, the infarct size was increased in the diabetic hearts as compared with the 16WC group. Morphometric analysis showed vascular density in the heart was significantly increased in 2WD group as compared with the 2WC （by 28%） while there was decreased （by 33%） in 16WD compared with 16WC group. VEGF expression increased in 2WI） group by 30%, but was lower in 16WI） rats than in 16WC rats. [Conclusion] Short- and long-term STZ induced diabetes exert opposite influences on myocardial I/R injury, and these contradictory influences may depend on different alterations in VEGF expression and angiogenesis.