MicroRNA-155对糖尿病大鼠脑缺血损伤血管再生的调控

Effect of microRNA-155 on regulation of angiogenesis in diabetic rats with cerebral ischemic injury

目的:观察microRNA-155(miRNA-155)表达对糖尿病大鼠脑缺血损伤及CD31、血管内皮生长因子(VEGF)表达的影响,探讨miRNA-155对糖尿病加重脑缺血血管再生的调控作用。方法:SD大鼠腹腔内注射链脲佐菌素建立糖尿病大鼠模型,继而应用栓线法建立永久性局灶性脑缺血模型。随机分为5组:(1)假手术组(sham组);(2)脑缺血组(CI组);(3)糖尿病脑缺血组(DCI组);(4)糖尿病脑缺血+miRNA-155抑制物组(inhibitor组);(5)糖尿病脑缺血+阴性对照组(scramble组)。于缺血后24 h采用实时荧光定量聚合酶链反应检测miRNA-155的表达水平;参照Zea-Longa 5分制行神经功能缺损评分;2,3,5-氯化三苯基四氮唑(TTC)染色测梗死体积;Western blotting检测血小板内皮细胞黏附分子-1(PECAM-1/CD31)、VEGF的表达水平。结果:糖尿病脑缺血+miRNA-155抑制物组大鼠脑缺血侧皮质区的miRNA-155表达水平显著低于糖尿病脑缺血组(P<0.05)。miRNA-155表达下调可显著减少糖尿病脑缺血大鼠的神经功能缺损评分及脑梗死体积,但显著增加CD31表达水平与VEGF表达水平(均P<0.05)。结论:miRNA-155对糖尿病加重脑缺血损伤血管再生有重要的调控作用,miRNA-155表达下调可显著减轻糖尿病大鼠脑缺血损伤。

AIM： To evaluate the effect of microRNA-155（ miRNA-155） on the regulation of angiogenesis in diabetic rats with cerebral ischemic injury. METHODS： Adult male Sprague-Dawley rats were randomly divided into 5groups： sham group,cerebral ischemia group,diabetic cerebral ischemia group,diabetic cerebral ischemia ＋ miRNA-155 inhibitors group and diabetic cerebral ischemia ＋ scramble group. Diabetes model was made by injection of streptozocin and permanent cerebral ischemic model was developed by suture-occluded method. The scores of neurological deficit and infarct volume were estimated at 24 h after cerebral ischemia. miRNA-155 level was detected by real-time polymerase chain reaction. The expression of platelet endothelial cell adhesion molecule-1（ PECAM-1 / CD31） and vascular endothelial growth factor（ VEGF） was detected by Western blotting. RESULTS： miRNA-155 inhibitor significantly reduced miRNA-155 levels in the ischemic cortex（ P〈0. 05）,improved the scores of neurological deficit,reduced infarction size and upregulated the levels of CD31 and VEGF（ P〈0. 05）. CONCLUSION： miRNA-155 has a critical role in the regulation of angiogenesis in diabetic rats with cerebral ischemia. Down-regulation of miRNA-155 using miRNA-155 inhibitor attenuates brain infarct injury in diabetic rats.