Objective To investigate the effect of ERK on carotid endothelial dysfunction and inflammatory expression in type 1 diabetes. Methods Eight C57BL/6 wild type male mice were used as control animals;eight INS2AKITA male mice were put in type 1 diabetic group, treatment group included eight INS2AKITA male mice, intraperitoneally injected with PD98059 10 nag/kg each day for consecutive 8 weeks. Then,the mice were killed and serum Glu,NO,ET-l were measured, and NO,tNOS,MPO in carotid artery were also measured. HE staining was performed in carotid artery and immunohistology was performed to investigate MMP-9 protein expression in endothelial cell of carotid artery. The protein expression of p-ERK, ERK, MMP-9 in carotid artery was measured by Western blot, and STAT-3 DNA binding activity was measured by EMSA. Results Compared with control group, the expression of serum ET-1 and carotid MPO was increased prominently (P<0. 05) whereas serum and carotid NO was decreased, and the expressions of carotid p-ERK/ERK, MMP-9 was increased significantly; STAT-3 DNA binding activity was increased prominently (P< 0. 05). Compared with type 1 diabetic group, after treatment with PD98059,carotid MPO was decreased, and NO and tNOS were increased, and expressions of p-ERK/ERK and MMP-9 decreased (P< 0. 05); STAT-3 DNA binding activity decreased after treatment with PD98059(P<0. 05). Conclusions ERK signal pathway participated in carotid endothelial dysfunction and inflammatory expression via STAT-3 in type 1 diabetes.%目的 探讨细胞外调节蛋白激酶( ERK)在1型糖尿病小鼠颈动脉内皮功能紊乱及炎症表达中的作用.方法 选择C57BL/6野生型雄性小鼠8只为对照组,同窝INS2AKITA雄性小鼠16只分为1型糖尿病组和干预组,每组8只,分别腹腔注射0.1％DMSO 50 μl/d;PD98059 10 mg/(kg ·d),连续8周.检测血糖及NO、内皮素1水平,凝胶电泳迁移率实验检测颈动脉NO、一氧化氮合酶(NOS)、髓过氧化物酶(MPO)水平及信号转导与转录活化因子3(STAT-3)活性,Western blot检测ERK和基质金属蛋白酶9(MMP-9)蛋白表达,免疫组织化学检测颈动脉内皮MMP-9阳性表达.结果 与对照组比较,1型糖尿病组血清内皮素1和颈动脉MPO明显增高,血清和颈动脉NO、NOS明显减低(P＜0.05);ERK和MMP-9蛋白表达、颈动脉STAT-3活性及颈动脉内皮MMP-9阳性表达明显增高(P＜0.05).与1型糖尿病组比较,干预组上述各项均明显变化,差异有统计学意义(P＜0.05).结论 ERK信号途径可通过STAT-3参与1型糖尿病小鼠颈动脉内皮功能紊乱及MMP-9等炎性因子表达.
展开▼
