硝基酪氨酸在糖尿病大鼠胰岛中的表达及普罗布考的干预作用

目的观察硝基酪氨酸（NT）在糖尿病大鼠胰岛中的表达，以及普罗布考的干预对其表达和对胰岛β细胞的影响。方法大鼠高脂高糖饲料喂养4周后，腹腔注射链脲佐菌素30mg／kg复制2型糖尿病大鼠模型，普罗布考组（PB组）每天同时灌胃普罗布考500mg／kg，10周后测定空腹血糖（FPG）、空腹胰岛素（Fins）、总胆固醇（TC）、甘油三酯（TG）、丙二醛（MDA）、超氧化物歧化酶（SOD），计算胰岛素敏感指数（ISI），用免疫组化的方法观察NT在胰岛中的表达。结果糖尿病组（DM组）及PB组大鼠的FPG、TG、TC及MDA水平较正常对照组（NC组）明显增加（P〈0．01），NT的平均光密度也明显高于NC组（P〈0．01），但PB组上述指标的测定显著低于DM组（P〈0．01）；DM组和PB组大鼠的SOD水平、ISI明显低于NC组（P〈0．01），PB组这些指标的测定显著高于DM组（P〈0．01）；NC组和PB组的Fins比较差异没有统计学意义，但都明显高于DM组（P〈0．01）。结论NT在胰岛的表达增强，普罗布考作为抗氧化剂，对于STZ引起的或糖尿病引起的氧化应激，均在一定程度上减轻其损伤，保护了胰岛功能。

The nitrotyrosine expression in pancreatic islets of diabetic rats and the probucol effect on the islet function

Objective To investigate the expression of nitrotyrosine in pancreatic islets of diabetic rats, and the effect of probucol on the function of pancreatic islets. Methods Type 2 diabetes rats were induced by streptozotocin injection and high fat and sucrose diet. Probucol treatment （500mg/Kg） was accomplished for 10 weeks. We measured the serum levels of glucose, insulin, MDA and SOD, and calculated the insulin sensitivity index （ISI）. The expression of nitrotyrosine （NT） was observed by immunohistochemistry method. Results The levels of FPG,TG,TC and MDA of DM（diabetes） group and PB（probucol） group were significantly increased（P〈0. 01）. The average optical density of NT were much higher in DM and PB group than in NC（normal control） group（0.27±0.017 vs 0. 16±0. 021 vs 0. 027±0. 009, P〈0.01）, but the markers of PB group decreased significantly as compared with DM group（P〈0.01）. The level of SOD and value of ISI were much lower in DM and PB group than in NC group（P〈0.01）, however, the markers of PB group were higher than DM group （P〈0. 01）. The Fins level of NC and PB group had no significant difference （15.78 ± 0. 85 vs 15.03 ± 0.84）, whereas they increased significantly as compared with DM group. Conclusions The expression of nitrotyrosine in pancreatic islets is enhanced in diabetes. Probucol reduces the oxidative stress and restores the pancreatic islets function through an antioxidant action.