糖尿病早期脑损伤与线粒体功能障碍  

Early-onset type 1 diabetes causes brain injury and mitochondrial dysfunction

作　　者：耿喜林[1] 徐明丽 尹洁[3] 穆继英[3] 张朗[3] 景玉宏[3,4] 

机构地区：[1]兰州大学第二医院创伤外科,甘肃兰州730030 [2]甘肃省卫生学校药学教研室,甘肃兰州730000 [3]兰州大学基础医学院人体解剖与组织胚胎学研究所,甘肃兰州730000 [4]兰州大学基础医学院神经科学研究所,甘肃兰州730000

出　　处：《中国病理生理杂志》2012年第9期1571-1576,共6页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.30872731);甘肃省自然科学基金资助项目(No.1010RJZA114)

摘　　要：目的:研究1型糖尿病早期阶段脑损伤的主要病理原因,是否影响线粒体功能及其可能机制。方法:SD大鼠经股静脉单次注射链脲佐菌素(streptozotocin,STZ)诱导高血糖,持续高血糖2个月后,检测外周血、脑脊液及脑组织中葡萄糖、甘油三酯和总胆固醇水平。取大鼠前额皮层,分离线粒体,检测线粒体氧化及抗氧化水平,Western blotting检测腺苷酸活化蛋白激酶(AMP-activated protein kinase,AMPK)磷酸化水平。全脑冰冻切片,Fluo-Jade-C染色检测神经细胞损伤程度。电镜检测皮层锥体细胞自噬-溶酶体变化。结果:1型糖尿病神经损伤主要原因是高血糖,可以导致皮层Fluo-Jade-C阳性细胞增多,线粒体氧化水平升高,抗氧化能力下降,AMPK磷酸化水平下降。同时发现1型糖尿病大鼠皮层锥体细胞自噬体增多,自噬体内包裹有线粒体或线粒体残余。结论:1型糖尿病早期所致的脑损伤,与持续高血糖增加氧化应激,进而损伤线粒体功能有关,伴随有自噬激活。AIM： To explore the main risk factors of diabetic encephalopathy and to investigate the changes of mitochondria in early - onset type 1 diabetes. METHODS： Single dose of streptozotocin was injected through the femoral vein to establish type 1 diabetes model in rats. The levels of glucose, triglyeeride and cholesterol in plasma, cerebrospinal fluid and cerebral cortex were measured. Oxidative and antioxidative status was evaluated by determining the levels of malondialdehyde and glutathione in the isolated mitochondria of cerebral cortex. Furthermore, the level of active AMP - acti- vated protein kinase （AMPK） in the isolated mitochondria was detected by Western blotting. Degenerative neurons were i- dentified by Fluo - Jade - C staining in serial brain sections. Autophagy - lys0some was observed under electron microscope. RESULTS： The main risk factor in the development of diabetic encephalopathy was hyperglucemia, which in- creased the Fluo - Jade - C positive neurons in the cerebral cortex of diabetic rats. The content of malondialdehyde was increased and glutathione was decreased in diabetic rats compared with the control animals. The activity of AMPK was lower in diabetic brain than that in normal brain. Aggregated autophagysome and mitochondria enveloped by autophagy - lysosome were observed in pyramidal cells of cerebral cortex in diabetic rats. CONCLUSION： Persistent hyperglycemia and mito- chondrial dysfunction contribute to the diabetic encephalopathy at an early stage in type 1 diabetes, indicating that the mechanism may be partly related to the oxidative stress and activation of autophagy.

关 键 词：高血糖症 线粒体 自噬 脑 

分 类 号：R587.1[医药卫生—内分泌]