韦尼克脑病脑区选择性损害与转酮醇酶活性下降相关的实验研究

Decreased Activity of Transketolase is Related With Regionally Selective Damage of Brain Midline in Wernicke Encephalopathy

目的:研究硫胺素缺乏时转酮醇酶(TK)及其他硫胺素相关酶活性的改变,探讨韦尼克脑病脑区选择性损害的病理机制。方法:将雄性C57BL/6小鼠分为正常饲料对照组及硫胺素剥夺(TD)饲料组,硫胺素剥夺饲料组分为9d组和14d组,每组12只动物。实验结束后将动物处死取脑,检测TK、丙酮酸脱氢酶(PDH)、α-酮戊二酸脱氢酶(KGDH),及磷酸戊糖旁路关键酶6-磷酸葡萄糖脱氢酶(G6PD)活性,测定磷酸戊糖旁路产物辅酶Ⅱ(NADPH及NADP+)的含量。结果:硫胺素缺乏显著降低小鼠脑TK活性(P<0.05),但对PDH、KGDH活性未产生显著影响,且早期海马TK活性显著性降低,皮层TK活性无明显下降,海马G6PD活性有上升趋势但无统计学意义,脑NADPH合成显著下降。结论:转酮醇酶活性下降及其相关的磷酸戊糖代谢旁路功能障碍参与了韦尼克脑病中线脑区选择性损害的病理机制。

Objective：To explore the mechanism of brain regionally selective damage in Wernicke encephalopathy through studying the effects of thiamine deficiency on the activities of brain transketolase and other thiamine-related enzymes. Methods： Male C57BL/6 mice were divided into three groups. Control group mice received normal diet containing thiamine. TD mouse model was produced through a thiamine-depleted diet. TD mice were divided into two groups according to the duration of TD diet. Activities of brain pyruvate dehydrogenase （PDH）, α-ketoglutamate dehydrogenase （KGDH）, glucose-6-phosphate dehydrogenase （G6PD）, and TK were investigated. contents of brain NADP＋ and NADPH were also determined. Results： TD did not affect the activities of brain PDH and KGDH in TD9 and TD14 groups. Hippocampal TK activity was higher than that of neocortical areas. TD decreased significantly the activities of hippocampal TK and the contents of brain NADPH in TD9 and TD14 groups, but did not significantly affect brain G6PD and neocortical TK activities. Conclsion： The dysfunction of pentose- phosphate cycle due to decreased TK activity is involved in regionally selective damage of brain midline in Wernicke encephalopathy.