摘要
目的:探讨1型糖尿病脑内自由基产生的铁代谢途径及线粒体氧化损伤水平。方法:利用链脲佐菌素(streptozotocin,STZ)股静脉单次注射(60 mg/kg)诱导大鼠糖尿病模型,2个月后检测血糖及脑脊液的葡萄糖水平。通过Western Blot技术检测额叶皮层内特异性转运蛋白(divalent metal transport,DMT1)及硫氧环蛋白1(thioredoxin,TR1)的表达水平;分离神经细胞线粒体,检测线粒体中丙二醛(malonaldehyde,MDA)及谷胱甘肽(glutathione,GSH)的含量。结果:与正常组比较,STZ诱导的糖尿病模型大鼠在2个月时的血糖和脑脊液葡萄糖水平持续升高(P<0.05),前额叶皮层DMT1表达增加,而TR1的表达减少(P<0.05)。同时还观察到额叶皮层神经细胞线粒体GSH水平下降,而MDA的水平升高(P<0.05)。结论:糖尿病导致的神经细胞损伤和自由基累积关系密切,而铁代谢异常可能是原因之一,线粒体损伤可能是启动因素。
Objective： Iron metabolic pathway and mitochondrial oxidative level were investigated in the frontal cortex of type 1 diabetic rats. Methods： Streptozotocin （STZ） was injected through femoral vein （60 mg/kg） at one time. Two months after STZ injection, glucose of cerebral spinal fluid （CSF） and plasma was detected respectively. Expression of divalent metal transport （DMT1） and thioredoxin （TR1） in the frontal cortex were measured using Western Blot. Mito- chondria was isolated from frontal cortex and the levels of malonaldehyde （MDA） and glutathione（GSH） on mitochondria were evaluated. Results： Both of plasma- and CSF glucose increased in diabetic rats 2 months after STZ injection com- pared with the normal rats （ P 〈 0.05 ）. DMT1 expression increased and TRI expression decreased in the frontal cortex of diabetic rats compared with these in normal rats （P 〈 0.05 ）. Consistently, the level of GSH decreased and MDA in- creased in mitochondria of the frontal cortex in diabetic rats compared with these in normal rats （ P 〈 0.05 ）. Conclusion ： Brain injury induced by diabetes mellitus is closely related to accumulation of free radical, which may originated from the abnormal iron metabolism and targeted on mitochondria.
出处
《神经解剖学杂志》
CAS
CSCD
北大核心
2015年第4期445-449,共5页
Chinese Journal of Neuroanatomy
基金
国家自然科学基金(81370448)
兰州大学中央高校基本科研业务费专项资金(zujbky-2014-k17)
甘肃省自然科学基金(145RJZA073)
教育部留学人员回国项目资助
关键词
糖尿病脑病
铁代谢
线粒体
链脲佐菌素
大鼠
diabetic encephalopathy
iron metabolism
mitochondria
streptozotocin
rats
