细胞外调节蛋白激酶在1型糖尿病颈动脉内皮及炎症表达中的作用  

Effects of ERK signaling pathway on endothelium and inflammatory expression in carotid artery in type 1 diabetic mice

作　　者：王启章[1,2,3] 陈茂刚[1,2] 李达文[1,2] 刘朝来[1,2] 徐格林[1,2] 刘新峰[1,2] 

机构地区：[1]南方医科大学南京临床学院 [2]南京军区南京总医院神经内科,210002 [3]广州医学院附属深圳沙井医院神经内科

出　　处：《中华老年心脑血管病杂志》2011年第11期977-981,共5页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：国家自然科学基金(81000501;81000502)

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INS2^(AKITA)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 50μl/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。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.

关 键 词：细胞外信号调节MAP激酶类 糖尿病 1型 颈动脉疾病 内皮 血管 基质金属蛋白酶9 

分 类 号：R587.1[医药卫生—内分泌] R743.3[医药卫生—内科学]