p38促分裂原活化蛋白激酶在高脂饮食1型糖尿病小鼠颈动脉损伤后内膜增生中的作用  

Effect of p38MAPK on intimal hyperplasia in type 1 DM mice on a high fat dietafter carotid endovascular injury

作　　者：王启章[1,2] 陈茂刚 徐格林[1] 刘新峰[1] 

机构地区：[1]南京军区南京总医院神经内科,210002 [2]广州医科大学附属深圳沙井医院神经内科 [3]江苏省盐城市第一人民医院急诊科

出　　处：《中华老年心脑血管病杂志》2016年第8期855-858,共4页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：国家自然科学基金(81471181;81400332)

摘　　要：目的探讨p38促分裂原活化蛋白激酶(p38MAPK)特异性抑制剂SB203580对高脂饮食1型糖尿病小鼠颈动脉血管内损伤后内膜增生的影响。方法选择雄性突变型INS2AKITA小鼠12只及同窝出生的野生型C57BL/6雄性小鼠6只,小鼠分为3组:对照组,高TC饮食组,干预组,每组6只。各组小鼠于颈动脉损伤后28d处死并取右颈总动脉。免疫组织化学检测内膜磷酸化p38MAPK、血管细胞黏附分子1(VCAM-1)及8-羟基脱氧鸟苷(8-OHdG)表达。结果与对照组比较,高TC饮食组术后28d管腔面积明显缩小,内膜面积、中膜面积、内膜/中膜面积、磷酸化p38MAPK、VCAM-1、8-OHdG表达水平明显增强(P<0.01)。与高TC饮食组比较,干预组术后28d管腔面积明显增加,内膜面积、中膜面积、内膜/中膜面积明显缩小,VCAM-1、8-OHdG、磷酸化p38MAPK表达明显降低(15.27±3.70 vs 28.39±5.33,P<0.05;8.75±3.32 vs 19.92±5.35,P<0.05;7.69±2.18 vs18.45±3.77,P<0.01)。结论 p38MAPK抑制剂可能主要通过减轻氧化应激及VCAM-1等炎性反应控制糖尿病高脂饮食小鼠颈动脉血管内损伤后内膜增生。Objective To study the effect of p38 MAPK specific inhibitor,SB203580,on intimal hyperplasia in type 1DM mice on a high fat diet.Methods Eighteen mice were divided into control group,high fat diet group,and SB203580 treatment group（6in each group）.The animals were killed 28 days after common carotid artery injury and their right common carotid artery were removed.Expression of p38 MAPK,VCAM-1,and 8-OHdG in carotid artery intima was detected with immunohistochemical staining.Results The area of carotid artery lumen,intima and media was significantly smaller,the ratio of intima/media（I/M）area was significantly higher,the expression level of VCAM-1,8-OHdG and p38 MAPK was significantly higher in high fat diet group than in control group 28 days after operation（P〈0.01）.The area of carotid artery lumen was significantly larger,the area of carotid artery intima and media was significantly smaller,the ratio of I/M area was significantly lower,the expression level of VCAM-1,8-OHdG and the serul p38 MAPK level was significantly lower in SB203580 treatment group than in high fat diet group28 days after operation（P〈0.05,P〈0.01）.Conclusion SB203580 controls the intimal hyperplasia in type 1DM mice on a high fat diet after carotid endovascular injury by inhibiting the oxidative stress and down-regulating the VCAM-1expression.

关 键 词：P38丝裂原活化蛋白激酶类 糖尿病 1型 颈动脉损伤 

分 类 号：R743[医药卫生—神经病学与精神病学]