Figliomeni B, Bacci B, Panozzo C, Fogarolo F, Triban C, Fiori M G
FIDIA Research Laboratories, Abano Terme, Italy.
Diabetes. 1992 Jul;41(7):866-71. doi: 10.2337/diab.41.7.866.
Abnormalities in axonal transport of proteins are thought to play an important role in the pathogenesis of diabetic neuropathy. Gangliosides exert a positive action on numerous alterations in biochemistry and physiology of diabetic nerves. This study was undertaken to assess the effects of exogenous gangliosides on the axonal transport of structural proteins such as actin and tubulin in the sensory fibers of short-term (9-wk) and long-term (6-mo) diabetic rats. Adult Sprague-Dawley rats were made diabetic with a single injection of 70 mg/kg streptozocin i.p. Subgroups were injected daily with either highly purified ganglioside mixture (10 mg/kg i.p.) or saline for 1 mo, beginning either 2 or 17 wk after streptozocin injection. Age-matched rats were used as controls. Axonal transport was studied by the pulse-labeling technique. Three weeks after labeling, sciatic nerves were dissected out and processed for sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography. In diabetic rats of both experimental designs, the transport rate of tubulin and actin was decreased by approximately 30% compared with control rats. Ganglioside treatment counteracted such alterations in both 9-wk and 6-mo diabetic rats. These data suggest a pharmacological effect that could be correlated with molecular interactions between integral membrane glycolipids and cytoskeletal elements.
蛋白质轴突运输异常被认为在糖尿病性神经病变的发病机制中起重要作用。神经节苷脂对糖尿病神经的生物化学和生理学的多种改变具有积极作用。本研究旨在评估外源性神经节苷脂对短期（9周）和长期（6个月）糖尿病大鼠感觉纤维中肌动蛋白和微管蛋白等结构蛋白轴突运输的影响。成年Sprague-Dawley大鼠腹腔注射70mg/kg链脲佐菌素使其患糖尿病。在链脲佐菌素注射后2周或17周开始，各亚组每天腹腔注射高纯度神经节苷脂混合物（10mg/kg）或生理盐水，持续1个月。以年龄匹配的大鼠作为对照。采用脉冲标记技术研究轴突运输。标记后3周，取出坐骨神经，进行十二烷基硫酸钠-聚丙烯酰胺凝胶电泳和荧光显影处理。在两种实验设计的糖尿病大鼠中，与对照大鼠相比，微管蛋白和肌动蛋白的运输速率降低了约30%。神经节苷脂治疗可抵消9周和6个月糖尿病大鼠的此类改变。这些数据表明了一种药理学效应，这可能与完整膜糖脂和细胞骨架成分之间的分子相互作用有关。
