大豆异黄酮对I型糖尿病甲基乙二醛水平及白内障并发症的影响

目的：甲基乙二醛（MG）是糖代谢产生的毒性副产物,本研究旨在探讨大豆异黄酮是否通过降低MG的产生而发挥对I型糖尿病的防治作用。方法：链脲佐菌素诱导I型糖尿病大鼠模型,给予含不同剂量大豆异黄酮的大鼠饲料喂养,按大豆异黄酮不同剂量随机分为3组：大豆异黄酮低剂量组（diabetes+LIS）,大豆异黄酮高剂量组（diabetes+HIS）及模型组（diabetes）。治疗8周后处死大鼠,留取血清测定血糖、糖化血红蛋白、还原型谷胱甘肽（GSH）、胰岛素水平,HPLC法测定血清MG水平,免疫组化法检测胰岛β细胞胰岛素表达情况。结果：与模型组或diabetes+LIS组大鼠比较,HIS组大鼠血清胰岛素水平明显上升［(2.46±0.35)μg/L vs (0.55±0.04)μg/L or (0.39±0.04) μg/L, 均P<0.01］,血糖明显下降［(19.50±1.85)mol/L vs (28.24±3.56) mol/L or (26.94±1.82) mmol/L, 均P<0.05］、糖化血红蛋白减低［（13.14±3.00)% vs (17.16±2.60)% or (17.29±4.12)%, 均P<0.05］,血清MG明显降低 ［(0.77±0.09)nmol/L vs (1.57±0.17)nmol/L or (1.91±0.28)nmol/L,均P<0.05］,而血清GSH 水平明显增加［(13.26±1.61)mmol/L vs (7.35±1.55)mmol/L or (5.54±1.10) mmol/L, 均P<0.01］,diabetes+HIS 组大鼠胰岛β细胞中胰岛素表达水平也明显增加。Diabetes+HIS 组大鼠白内障的发生率明显低于模型组（P<0.05）。模型组与diabetes+LIS组比较,上述指标均无显著差异。结论：大豆异黄酮对I型糖尿病具有治疗作用,并能降低I型糖尿病大鼠白内障的发生率,其机制可能与胰岛素水平增加、MG水平降低及抗氧化作用有关。     

Methylglyoxal-induced mitochondrial dysfunction in vascular smooth muscle cells

The effects of methylglyoxal (MG) on mitochondria with specific foci on peroxynitrite (ONOO⁻) production, manganese superoxide dismutase (MnSOD) activity, and mitochondrial functions in vascular smooth muscle A-10 cells were investigated. Mitochondrial MG content was significantly increased after A-10 cells were treated with exogenous MG, and so did advanced glycated endproducts (AGEs) formation, indicated by the appearance of N_?-(carboxyethyl) lysine, in A-10 cells. The levels of mitochondrial reactive oxygen species (mtROS) and ONOO⁻ were significantly increased by MG treatment. Application of ONOO⁻ specific scavenger uric acid lowered the level of mtROS. MG significantly enhanced the production of mitochondrial superoxide (O₂⁻) and nitric oxide (NO), which were inhibited by SOD mimic 4-hydroxy-tempo and mitochondrial nitric oxide synthase (mtNOS) specific inhibitor 7-nitroindazole, respectively. The activity of MnSOD was decreased by MG treatment. Furthermore, MG decreased respiratory complex III activity and ATP synthesis in mitochondria, indicating an impaired mitochondrial respiratory chain. AGEs cross-link breaker alagebrium reversed all aforementioned mitochondrial effects of MG. Our data demonstrated that mitochondrial function is under the control of MG. By inhibiting Complex III activity, MG induces mitochondrial oxidative stress and reduces ATP production. These discoveries will help unmask molecular mechanisms for various MG-induced mitochondrial dysfunction-related cellular disorders.