吡哆胺对糖尿病大鼠视皮质AGE-RAGE系统的影响

目的观察吡哆胺对糖尿病大鼠视皮质高级糖基化终末产物(AGE)及其受体(RAGE)表达的影响,探讨吡哆胺对视皮质的保护作用。方法健康SD大鼠随机分为正常对照组(NC组)、糖尿病未治疗组(DM组)、糖尿病吡哆胺治疗组(PM组)和氨基胍治疗对照组(AG组)各20只,用链脲佐菌素(STZ)建立糖尿病模型,PM组和AG组分别于造模成功后第二天开始予吡哆胺和氨基胍灌胃。各组于治疗4w和12w后取材,用酶联免疫吸附(ELISA)法定量检测大鼠视皮质中AGEs含量,荧光免疫组化及图像分析半定量检测各组视皮质RAGE的表达。结果糖尿病治疗组和未治疗组血糖无显著性差异。4w时各组AGEs含量无明显差异,12w时PM组视皮质中AGEs含量与AG组、NC组比较差异无统计学意义,与DM组相比显著降低,差异具有统计学意义(P0.05)。PM组视皮质中RAGE表达比DM组显著减少,差异具有统计学意义(P0.05),但高于NC组(P0.05)。结论糖尿病大鼠12w后视皮质中AGEs含量和RAGE的表达高于正常对照组,吡哆胺类似氨基胍可减少AGEs的堆积,还能抑制RAGE的表达,减轻AGEs-RAGE通路作用导致的组织损伤,对视皮质具有一定的保护作用。

Effect of pyridoxamine on AGE and RAGE expression in the visual cortex in diabetic rats

Objective To observe the changes ot advanced glycosylation end products （AGEs） and their receptors （RAGEs）in the visual cortex, and to investigate the protective effect of pyridoxamine on the visual cortex of diabetic rats. Methods Sprague Dawley rats were randomly divided into 4 groups ： normal control （NC）,diabetes mellitus （DM）, pyridoxamine （PM）,and aminoguanidine （AG）. Diabetes was in duced by intraperitoneal injection of STZ （65 mg/kg） . Rats were treated with either pyridoxamine （PM group） or aminoguanidine （AG group） after successful induction of diabetes mellitus. 4 and 12 weeks after the treatment, ELISA assay was conducted for the detection of AGEs, and immunofluoresence was used for semi quantitative analysis of RAGE expression in the visual cortex. Results No significant difference in blood glucose was identified among DM, PM and AG groups. The concentrations of AGEs from each group also showed no significant difference after 4 week treatment. After 12 weeks,the contents of AGEs in the visu al cortex of AG, PM and NC groups were significandy lower in contrast to the DM group（P〈0. 05）, while no significant difference was identified among the former 3 groups（P〉0. 05）. The expression of RAGEs in the visual cortex was significandy reduced in the PM group in comparison with that of the DM group（P〈0.05）, despite an increase in contrast to NC group. Conclusion TEe content of AGEs and the ex pression of RAGEs in the visual cortex of diabetic rats is higher than in the normal group. Although pyridoxamine has no effect on decreasing blood glucose, it plays a certain role in reducing the accumulation of AGEs and the ex pression of RAGEs in the visual cortex as aminoguanide does, which can alleviate the AGE RAGE padaway media ted injury and protect the visual cortex to some extent.