【摘要】 目的:探究维生素D(Vit-D)对糖尿病(DM)大鼠模型主动脉中层厚度的影响及其蛋白激酶受体样内质网激酶(PERK)和真核翻译起始因子2α(eIF2α)(PERK/eIF2α)通路的作用机制。方法:选用30只Sprague-Dawley(SD)雄性大鼠,采用随机数表法将其分为对照组、DM组和DM+Vit-D组,每组10只。通过给每只大鼠腹腔注射链脲佐菌素建立大鼠DM模型,DM+Vit-D组大鼠使用活性形式的Vit-D3灌胃(0.1μg·kg-1·d-1)。比较各组大鼠的血糖水平、主动脉损伤情况、血清一氧化氮(NO)和内皮素(ET)水平,并采用Westernblot检测主动脉组织中PERK/eI F2α通路中的蛋白表达水平。结果:DM模型大鼠的血糖水平均>16.7 mmol·L-1,干预后DM组和DM+Vit-D组的尾静脉空腹血糖(FBG)水平差异无统计学意义。DM组的收缩压和脉搏波传导速度(PWV)显著高于对照组,其差异有统计学意义(t=5.263, t=4.956,P<0.05);DM+Vit-D组的收缩压和PWV显著低于DM组,其差异有统计学意义(t=5.016, t=4.332;P<0.05)。DM组大鼠的主动脉中层厚度[(103.24±4.98)μm]显著高于对照组[(90.15±3.24)μm],DM+Vit-D组的主动脉中层厚度[(96.74±4.21)μm]显著低于DM组[(80.25±2.86)μm],差异有统计学意义(t=3.521,t=3.852;P<0.05)。DM组的NO水平为(51.49±6.85)μmol·L-1显著降低、ET水平为(110.28±11.39)pg·ml-1显著升高,与对照组比较差异有统计学意义(t=4.585,t=5.677;P<0.05);DM+Vit-D组的NO水平[(61.18±8.21)μmol·L-1]显著升高,ET水平[(101.44±11.32)pg·ml-1]显著降低,与DM组比较差异有统计学意义(t=5.029,t=5.881;P<0.05)。DM组大鼠的PERK和eIF2α蛋白水平显著高于对照组,差异有统计学意义(t=3.612,t=4.083;P<0.05);DM+Vit-D组的PERK和eIF2α蛋白水平显著低于DM组,差异有统计学意义(t=3.506,t=3.892;P<0.05)。结论:Vit-D可通过抑制DM大鼠的主动脉中PERK/eI F2α通路水平,缓解主动脉损伤和血管内皮功能。更多还原

【Abstract】 Objective: To explore the effects of vitamin D(Vit-D) on the thickness of middle-layer of aorta in the diabetes mellitus(DM) rat and the mechanism of action of the pathway of protein kinase receptor like endoplasmic reticulum kinase(PERK) and eukaryotic translation initiation factor 2 α(eIF2 α)(PERK/eIF2 α). Methods: Thirty Sprague Dawley(SD) male rats were randomly divided into control group, DM group and DM + Vit-D group, with 10 rats in each group. DM model was established by intraperitoneal injection of streptozotocin to each rat in DM group. Rats in DM + Vit-D group received gavage with active form of Vit-D3(0.1 μ g·kg-1·d-1). The levels of blood glucose, aortic injury, serum nitric oxide(NO) and endothelin(ET) of among different groups were compared, and Western blot was adopted to detect the expression levels of proteins in PERK/eIF2 pathway of aortic tissue. Results: The blood glucose level of all DM model rats was larger than 16.7 mmol·L-1. After intervention, there was no significant difference in the level of fasting blood glucose(FBG) of caudal vein between DM group and DM + Vit-D group. Systolic blood pressure and pulse wave velocity(PWV) in DM group were significantly higher than those in control group(t=5.263, t=4.956, P<0.05), respectively. Systolic blood pressure and PWV in DM + Vit-D group were significantly lower than those in DM group(t=5.016, t=4.332, P<0.05). The thickness of aortic middle layer of DM group [(103.24±4.98) μ m] was significantly higher than that of control group [(90.15±3.24) μ m]. The thickness of aortic middle layer in DM + Vit-D group [(96.74 ± 4.21) μ m] was significantly lower than that in DM group [(80.25±2.86) μ m], the differences of them between two groups were statistically significant(P<0.05). Compared with the control group, the level of NO [51.49±6.85] was significantly decreased and the level of ET [110.28 ± 11.39] was increased significantly in DM group(t=4.585, t=5.677, P<0.05). NO level in DM + Vit-D group [(61.18±8.21) μmol·L-1] was increased, and the ET level of that group [(101.44±11.32) PG · mol·L-1] was significantly decreased, and the differences of them between DM+ Vit-D group and DM group were significant(t=5.029, t=5.881, P<0.05). PERK and eIF2α protein in DM group were significantly higher than those in control group(t=3.612, t=4.083, P<0.05), respectively. The levels of PERK and eIF2α of DM + Vit-D group were significantly lower than those of DM group(t=3.506, t=3.892, P<0.05), respectively. Conclusion: Vit-D can relieve aortic injury and vascular endothelial function through inhibits the pathway level of PERK/eIF2α in aorta of DM rats.更多还原