中文摘要：

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％DMSO50μl／d；PD9805910mg／（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（MP0）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。

英文摘要：

Objective To investigate the effect of ERK on carotid endothelial dysfunction and in-flammatory expression in type I 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 mg/kg each day for consecutive 8 weeks. Then, the mice were killed and serum Glu, NO, ET-1 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 imcreased 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 endotheli- al dysfunction and inflammatory expression via STAT-3 in type 1 diabetes.