Exendin-4对2型糖尿病大鼠主动脉内皮核因子-κB和细胞间黏附分子-1表达的影响

Effect of exendin-4 on the expression of NF-κB p65 and ICAM-1 in aorta endothelium of type 2 diabetic rats

目的探讨Exendin-4对2型糖尿病大鼠主动脉内皮NF-κB p65以及细胞间黏附分子-1(ICAM-1)表达的影响。方法选择40只雄性SD大鼠,6只喂基础饲料为正常对照组(NC组),另34只喂高脂饲料4周后,一次性腹腔注射链脲佐菌素,建立2型糖尿病大鼠模型,维持2周,24只大鼠造模成功,并分为糖尿病组(DM组)、Exendin-4低剂量治疗组(GL组)、中剂量治疗组(GM组)、高剂量治疗组(GH组),每组6只,给予不同剂量Exendin-4腹腔注射治疗6周。心脏采血检测丙二醛(MDA)、超氧化物歧化酶(SOD)、总抗氧化能力(T-AOC)水平。之后分离胸主动脉,免疫组织化学方法观察主动脉内皮NF-κB p65和TCAM-1的表达。结果与NC组比较,DM组MDA升高,SOD和T-AOC降低(P<0.05)。与DM组比较,GH组MDA降低,SOD、T-AOC升高;且NF-κB p65表达明显降低(P<0.05)。与GL组比较,GM组、GH组ICAM-1表达明显降低,差异均有统计学意义(P<0.05)。结论 Exendin-4具有血管内皮保护作用,其机制与抗氧化、抑制血管内皮NF-κB p65、ICAM-1的活化有关。

Objective To explore the influence of exendin-4 on antioxidation index in serum and the expression of nuclear factor Kappa B （NF- κB）p65 and intercellular cell adhesion molecule-1 （ICAM-1） in aorta endothelium of type 2 diabetic rats and the possible mechanism. Methods The normal rats were injected with streptozocin（STZ） into abdominal cavity after high fat diet to establish the model of type 2 diabetic rats. Forty SD male rats were randomly divided into normal control group,diabetic model group and groups treated with low, medium,and high dose of exendin-4. The treated groups were treated with intraperitoneal injection of exendin-4 for six weeks. Heart blood was taken for examining biochemical indexes including malondialdehyde（MDA）,SOD and total antioxidation capability（T-AOC）. The thoracic aorta was isolated carefully to observe the expression of NF-κB p65 and ICAM-1 in endothelium with immunohistochemieal method. Results Exendin-4 could decrease the level of MDA,but increase the levels of SOD and T-AOC in type 2 diabetic rats. Treatment with exendin-4 could decrease the expression of NF-κB p65. The medium and high dose of exendin-4 could decrease the expression of ICAM-1 （P 〈20.05）. Conclu- sion Exendin-4 has function to protect aorla endothelium,the mechanism is related to the antioxidation and restraining activation of NF-κB p65 and ICAM-1 in the blood vessel endothelium.