孤独症患者前额叶皮层中有氧糖酵解酶的表达改变

Changes of expressions of aerobic glycolytic enzymes in prefrontal cortex of patients with autism

目的研究孤独症患者前额叶皮层中有氧糖酵解酶表达量的改变,明确糖代谢过程异常在孤独症发病机制中的作用,为临床新药的研发提供理论依据。方法采用Western blotting检测孤独症患者和年龄对照正常人尸脑前额叶皮层中有氧糖酵解酶hexokinaseⅠ、hexokinaseⅡ、PKM1/2、PKM2、PDH、GAPDH、LDHA及PFKP的表达;免疫组织化学方法检测两组前额叶皮层中hexokinaseⅡ的表达量。结果 Western blotting结果显示,与对照组相比,孤独症患者前额叶皮层中hexokinaseⅡ和PDH表达均减少,其他6种酶的表达均无显著差异。免疫组织化学结果显示,孤独症前额叶皮层神经细胞中hexokinaseⅡ表达减少。结论前额叶皮层中hexokinaseⅡ和PDH的表达减少与孤独症脑组织中糖代谢受损相关,可能参与孤独症的发病过程。

Objective To investigate changes of expressions of aerobic glycolytic enzymes in prefrontal cortex of patients with autism, identify the role of abnormal glucose metabolic process in the pathogenesis of autism, and provide the theoretical basis for the development of new drugs. Methods The Western blotting was adopted to detect expressions of aerobic glycolytic enzymes, including hexokinase I , hexokinase Ⅱ, PKM1/2, PKM2, PDH, GAPDH, LDHA, and PFKP in the prefrontal cortex of patients, with autism and age-matched controls. The expression of hexokinase lI in the prefrontal cortex of patients with autism and age-matched controls was detected by the immunohistochemical method. Results The results of Western blotting indicated that compared with controls, expressions of both hexokinase Ⅱ and PDH in prefrontal cortex of patients with autism significantly decreased, while expressions of other six enzymes showed no significant changes. The results of immunohistochemistry showed that the expression of hexokinase Ⅱ in neural cells of prefrontal cortex of patients with autism decreased. Conclusion The decrease of hexokinase Ⅱ and PDH expressions in prefrontal cortex of patients with autism is relevant to the impaired glucose metabolism in brain tissue and may involve in the development of autism.