P58IPK基因在糖尿病鼠视网膜中表达的动态变化

摘要

背景糖尿病视网膜病变(DR)的分子生物学发病机制仍不清楚,以往的研究表明内质网应激相关因子在糖尿病患者外周血中呈高表达,而P58 IPK 可以抑制这些因子的表达,因此P58 IPK 和糖尿病之间的关系值得深入研究.目的检测P58 IPK 在糖尿病大鼠模型视网膜中的动态表达,为进一步研究P58 IPK 抑制DR的机制奠定基础.方法 18只SD大鼠腹腔注射60 mg/kg链脲佐菌素(STZ)制作糖尿病动物模型,分别于造模后1、3、6个月各处死6只大鼠;另6只匹配的正常SD大鼠作为正常对照组.取视网膜组织采用实时定量聚合酶链反应(real-time PCR)法检测P58 IPK mRNA在大鼠视网膜中的表达,观察P58 IPK mRNA随糖尿病的发展出现的动态变化.结果造模后糖尿病组大鼠表现出多饮、多食、多尿,血糖均≥16.5 mmol/L,造模成功率为100%.造模后1个月、3个月鼠视网膜中P58 IPK mRNA/β-actinm RNA 的A值分别为0.800±0.005和0.975±0.008,明显高于对照组的0.725±0.006,差异有统计学意义(t=22.589、t=62.784,P＜0.05),造模后6个月鼠视网膜P58 IPK/β-actin的A值为0.671±0.004,并明显低于对照组,差异有统计学意义(t=-17.984,P＜0.05).结论 P58 IPK 参与DR的发病机制,可能具有延缓DR发生和发展的作用.%Background The molecular biological mechanisms of diabetic retinopathy(DR)is unclear up to now.Researches have proved that endoplasmic reticulum stress(ER Stress)-associated factors are elevated in peripheral blood in patients with diabetic retinopathy.and P58 IPK can inhibit those factors.So the relationship between P58 IPK and DR is worth to investigate. Objective The aim of this study was to detect the dynamic expression of P58 IPK in the retina of diabetic rats. Methods The diabetic animal models were established in 18 clean male SD rats by intraperitoneal injection of stilptozotiein(STZ)at a dose of 60 mg/kg.The rats were sacrificed in 1,3,6 months after injection.The expression change of P58 IPK mRNA in the rats retina was detected by quantitative real-time RT-PCR.Other 6 matched normal rats were used as control groups.This experiment followed the Regulations for the Administration of Affair Concerning experimental Animals by State Science and Technology Commission. Results The rats showed more drinking,more food and more urine after STZ injection with the blood glucose level≥ 16.5 mmol/L.The success rate of diabetic models was 100%.The A value of P58 IPK mRNA/β-actin in rat retina was 0.800±0.005 and 0.975±0.008 after injection of STZ.and that of control rats was 0.725±0.006,showing statistically significant difference between them(t=22.589,t=62.784,P＜0.05).In 6 months after injection of STZ,the expression of P58 IPK mRNA in experimental diabetic rat retina was evidently lower than the eontrol rats(0.671±0.004 versus 0.725±0.006,t=-17.984,P＜0.05).Conclusion P58 IPK has a close relation to the pathogenesis of DR,and it plays a retarding role for DR.