
血管性痴呆小鼠海马线粒体复合体活性变化
Changes of mitochondrial complex activity in vascular dementia mice
目的:探讨血管性痴呆(VD)小鼠海马线粒体复合体活性变化。方法:抽取并回输约40%总血量加双侧颈总动脉夹闭20 min建立VD模型。病理学研究检测神经元损伤;分光光度计法检测丙二醛(MDA)含量、锰超氧化物歧化酶(Mn-SOD)活性和线粒体复合体活性;Western-blot检测Mn-SOD蛋白表达;Morris水迷宫评估学习记忆能力。结果:与假手术组相比,模型组学习记忆能力显著降低(P<0.05),MDA含量显著升高(P<0.05),Mn-SOD活性和蛋白表达显著降低(P<0.05);与假手术组相比,术后5 d模型组线粒体复合体Ⅰ、Ⅱ、Ⅲ、Ⅳ活性显著降低(P<0.05),术后15,30 d和60 d模型组线粒体复合体Ⅰ、Ⅱ活性无显著变化(P>0.05),复合体Ⅲ、Ⅳ活性显著降低(P<0.05);病理学检测显示模型组海马出现进行性神经元损伤。结论:线粒体复合体III、IV活性异常可能是VD的发病机制之一。
OBJECTIVE To investigate changes of mitochondrial complex activity in vascular dementia (VD) mice. METHODS VD model was established through drawing out and reperfusing 40% of whole blood volume plus clamping carotid arteries of mice for 20 min. Histological observation was performed to evaluate neural damage. Malonaldehyde (MDA), manganese superoxide dismutase (Mn-SOD) and mitochondrial complex activity were determined by using spectrophotometer. Expression of Mn-SOD was tested by western blot, learning and remembering ability were determined by Morris water maze. RESULTS Compared with sham operation group, MDA level was increased in I/R group (P<0.05). Activity and expression of Mn-SOD, learning and remembering ability were decreased in mice in model group (P<0.05). Activities of mitochondrial complex Ⅰ,Ⅱ, Ⅲ and Ⅳ in model group were lower than those in sham operation group in the 5 th day (P<0.05). In the 15th, 30 th and 60 th days, activities of complex Ⅲ and Ⅳ of model group were lower than those in sham operation group (P<0.05), but no significant difference was observed between model group and sham operation group in complex Ⅰ and Ⅱ activities (P>0.05). Progressive neural damages were observed in model group. CONCLUSION Abnormal activities of mitochondrial complex Ⅲ and Ⅳ may be involved in mechanisms of VD.
血管性痴呆 / 记忆 / 线粒体 / 锰超氧化物歧化酶 {{custom_keyword}} /
vascular dementia / memory / mitochondria / Mn-SOD {{custom_keyword}} /
[1] Iemolo F, Duro G, Rizzo C, et al. Pathophysiology of vascular dementia
[J]. Immunity Aging, 2009, 6:13-21.
[2] Korczyn AD, Vakhapova V, Grinberg LT. Vascular dementia
[J]. J Neurol Sci, 2012, 322(1-2):2-10.
[3] 袁野, 杨俊卿, 周岐新. 脑缺血/再灌注致神经元退行性变进程中自由基水平和SOD1表达的关系
[J]. 第三军医大学学报, 2011,33(12):1211-1215.
[4] Danial NN, Korsmeyer SJ. Cell death: critical control points
[J]. Cell, 2004, 116(2):205-219.
[5] Chomova M,Tatarkova Z,Dobrota D, et al. Ischemia-induced inhibition of mitochondrial complex Ⅰ in rat brain: effect of permeabilization method and electron acceptor
[J]. Neurochem Res, 2012, 37(5):965-976.
[6] 崔丽霞, 郭锋, 李新毅. β-淀粉样蛋白与载脂蛋白E4对大鼠海马突触素的影响
[J].山西医科大学学报, 2014, 45(6):443-447.
[7] Wiesmann M,Kiliaan AJ,Claassen JA. Vascular aspects of cognitive impairment and dementia
[J]. J Cereb Blood Flow Metab, 2013, 33(11):1696-1706.
[8] Galisova A, Baciak L, Jozefovicova M, et al. Pathophysiological rat model of vascular dementia: magnetic resonance spectroscopy, microimaging and behavioral study
[J]. Brain Res, 2014, 1568:10-20.
[9] Zuo L, Motherwell MS. The impact of reactive oxygen species and genetic mitochondrial mutations in Parkinson's disease
[J]. Gene, 2013, 10, 532(1):18-23.
[10] Yue Liu, David S. Barber, Ping Zhang, et al. Complex II of the mitochondrial respiratory chain is the key mediator of divalent manganese-induced hydrogen peroxide production in microglia
[J]. Toxicological Sciences, 2013, 132(2): 298-306.
[11] Yi Wen, Wenjun Li, Ethan C. Poteet, et al. Alternative mitochondrial electron transfer as a novel strategy for neuroprotection
[J]. J Biol Chem, 2011, 286(18):16504-16515.
[12] Flynn JM, Melov S. SOD2 in mitochondrial dysfunction and neurodegeneration
[J]. Free Radic Biol Med, 2013, 62:4-12.
[13] Deryabina Y, Isakova E, Sekova V, et al. Inhibition of free radical scavenging enzymes affects mitochondrial membrane permeability transition during growth and aging of yeast cells
[J]. J Bioenerg Biomembr, 2014,
[Epub ahead of print].
[14] Smuder AJ, Kavazis AN, Hudson MB, et al. Oxidation enhances myofibrillar protein degradation via calpain and caspase-3
[J]. Free Radic Biol Med, 2010, 49(7): 1152-1160.
国家自然科学基金资助项目(编号:81070972)
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