NF-κB在糖尿病大鼠动脉粥样硬化作用机制的研究

目的探讨NF-κB在糖尿病大鼠动脉粥样硬化病变形成中的作用。方法Wistar大鼠随机分三组：链脲佐菌素诱导的糖尿病组（DM组）、NAC治疗组（NAC组）、对照组（C组）。分别于4w、8w、12w、16w检测血糖、胆固醇（TC）、甘油三酯（TG）、糖化血红蛋白（HbA1C）水平。于相应时间分别处死大鼠并分离和摘取主动脉,采用SP免疫组化或凝胶电泳迁移率（elec-trophoretic mobility Shift assay,EMSA）方法测定主动脉内皮NF-κB的DNA结合活性。结果①DM组、NAC组的血糖及HbA1C水平显著高于C组。②DM及NAC二组的TC、TG在4w、8w无显著变化,TC、TG在12w、16w时显著高于C组。③在12w、16w时,NF-κB结合活性在DM大鼠主动脉较对照组明显增强,NAC组较DM组减弱。④HE染色在DM组于12w、16w时出现AS的早期病理改变,而在NAC和C组未发现AS的病理改变。结论①DM大鼠大血管存在NF-κB的激活,并启动下游靶基因粘附分于ICAM-1的表达,进而导致DM大鼠动脉粥样硬化的发生与发展。因此NF-κB的激活可能是导致DM大鼠AS的始动因子之一。②高血糖是NF-κB不适当激活的又一因素,因此早期有效的控制血糖是防治DM鼠AS的基本策略。

Study on NF-κB Activation in the Pathogenesis of Atherosclerosis in Diabetic Rats

Objective To explore the role of the activated NF-κB in pathogenesis of the atherosclerosis in diabetic rats and the relation between NF-κB activation and the expression of ICAM-1.Methods Wistar rats were randomly divided into three groups： the control （group C）streptoxotocin-induced diabetic rats （group DM）,N-acetylcysteine-treated diabetic rats（group NAC）. After 1,2,3 and 4 months,all rats were killed,respectively,and following items in the plasma were determined ：HbA1 C, triglyceridc （TG）, total cholesterol （TC）, high density lipoproteins （HDL）. The NF-κB activation was analyzed by electrophoretic mobility shift assay （EMSA）.Results ①The levels of blood glucose and HbA1C in group DM and group NAC were significantly elevated as compared with group C. ②The level of blood lipids in group DM and group NAC was not increased after 1,2 months,but was raised after 3,4 months,respectively,compared with group C,and not reached the criterion of dyslipidimia. ③NF-κB was significantly activated in diabetic rats after 3,4months.Conclusions ①NF-κB in significantly activated in aorta of diabetic rats,and induces the expressions of its target genes,such as ICAM-1 and the like,and cause the development of atherosclerosis in diabetic rats.The NF-κB activation may be the key factor leading to the development of atherosclerosis in diabetic rats. ②Hyperglycemia may contribute to the NF-κB activation,so strict control of hyperglycemia as early as possible may prevent the development of atherosclerosis in diabetic rats.