ERK抑制剂对1型糖尿病模型小鼠血管内损伤后内膜增生的抑制作用

Inhibition Effect of ERK Inhibitor on Intimal Hyperplasia after Carotid Endovascular Injury in Type 1 Diabetes Model

目的探讨细胞外信号调节激酶(ERK)特异性抑制剂PD98059对1型糖尿病模型血管内损伤后内膜增生的抑制作用。方法将实验动物分为3组,假手术组,1型糖尿病模型血管内损伤组,PD98059干预组。各组小鼠于颈动脉损伤后第28天处死并取右颈总动脉,检测颈动脉管腔面积、内膜面积、中膜面积及内膜/中膜面积比(I/M)。免疫组化检测内膜抗磷酸压ERK(p-ERK)、基质金属蛋白酶-9(MMP-9)表达水平。结果与假手术组相比,1型糖尿病模型血管内损伤组术后28 d,管腔面积明显缩小,内膜面积、中膜面积及I/M明显增加,差异有统计学意义(P<0.01),颈动脉血管内膜p-ERK及MMP-9水平也明显增强(P<0.01)。PD98059干预组术后28 d,与1型糖尿病模型血管内损伤组相比,管腔面积明显增加,内膜面积、中膜面积及I/M明显降低(P<0.01),颈动脉内膜MMP-9表达明显减低,血脂及血糖水平无统计学意义。结论 ERK抑制剂可能通过抑制MMP-9减轻1型糖尿病高胆固醇饮食模型颈动脉血管内损伤后内膜增生。

Objective To investigate the inhibition effect of extracel ular signal regulated kinase(ERK)inhibitor on intimal hyperplasia after carotid endovascular injury.Methods The mice were divided into 3 groups:sham operation group,model group(type 1 diabetes model underwent damage of right common carotid artery),PD98059 treatment group.HE staining was performed in carotid artery and Image Pro Plus 6.0 image analysis software was used to measure the lumen area,intimal area,medial area and intima/media area ratio (I/M).Immunohistochemical staining was performed to detect the expressions of p ERK and matrix metal oproteinase 9 (MMP 9) in carotid intima.Results Compared with sham operation group,the lumen area was decreased,the intimal area,medial area and I/M,the expressions of p ERK and MMP 9 in carotid intima were significantly increased at 28 days after procedure in model group (P<0.01).Compared with model group,the lumen area was increased,the intimal area,medial area and I/M were decreased at 28 days after procedure in PD98059 treatment group(P<0.05).The expressions of p ERK and MMP 9 were suppressed,but there was no statistical change for serum glucose,triglyceride (TG),total cholesterol (TC)in PD98059 treatment group.Conclusion ERK specific inhibitor can inhibit MMP 9 expression,and suppress intimal hyperplasia after carotid endovascular injury in type 1 diabetes mice with high cholesterol diet.