褪黑素对脑出血大鼠神经细胞mtDNA缺失及线粒体转录因子A表达的影响  

Effects of melatonin on mtDNA deletion and mtTFA expression of neurons in rats with intracerebral hemorrhage

作　　者：李晓峰[1] 封浑 覃艳艳[1] 韦旋[1] 韦俊杰[1] 陈志[1] 李燕华[1] 李吕力[1] 

机构地区：[1]广西壮族自治区人民医院神经内科,广西南宁530021

出　　处：《中风与神经疾病杂志》2014年第6期484-487,共4页Journal of Apoplexy and Nervous Diseases

基　　金：广西自然科学基金(桂科青0542040)

摘　　要：目的观察褪黑素对脑出血大鼠神经细胞mtDNA缺失、线粒体转录因子A(mtTFA)表达的影响。方法 70只SD大鼠随机分为正常对照组、假手术组、脑出血模型组(模型组)、褪黑素治疗组(褪黑素组),组内随机分为12 h、1 d、2 d、4 d、7 d共5个时间点,应用修正神经功能缺损评分进行神经功能评估;应用荧光实时定量PCR技术对神经细胞mtTFA mRNA转录水平以及mtDNA缺失率进行定量分析;透射电镜技术观察神经元线粒体超微结构。结果脑出血后1 d^7 d褪黑素组神经功能评分低于模型组(P<0.05);脑出血后12 h^2 d时褪黑素组mtTFA mRNA表达显著高于模型组(P<0.05);褪黑素组mtDNA4834 bp缺失率低于模型组(P<0.05);模型组神经元线粒体肿胀、空泡化、数量减少,褪黑素组线粒体超微结构病理改变轻微。结论褪黑素能够上调脑出血大鼠神经细胞mtTFA表达,减少mtDNA4834 bp缺失,褪黑素可能通过保护线粒体功能从而发挥神经保护作用。Objective To observe the effect of melatonin on expression of mitochondrial transcription factor A （ mt- TFA） and mitochondrial DNA （mtDNA） deletion of neurons in rats with intracerebral hemorrhage （ICH）. Methods 70 SD rats were randomly divided into four groups：normal group, sham-operated group （Sham group） , intracerebral hemorrhage model group （Model group） and melatonin intervention group（ MT group）. Neurological function of rats were evaluated with modified Neurological Severity Scores（NSS） on 12 h, 1 d,2 d,4 d and 7 d after ICH respectively. The dynamic changes of mtTFA mRNA and the rate of mtDNA4834bp deletion were measured by Real-Time Polymerase Chain Reaction （ RT- PCR）. The uhrastructure of mitochondrial in neuronl was observed by electron microscope. Results The NSS score in MT group was lower than that in Model group from 1 d to 7 d after ICH （P 〈 0.05 ）. The expression of mtTFA mRNA in Model group was lower than that in MT group from 12 h to 2 d after ICH （P 〈 0.05 ）. The rate of mtDNA4834bp deletion in MT group was lower than that in Model group after ICH （ P 〈 0.05 ）. Electron microscope showed that the mitochondria were swollen and vacuolized, the numbers of mitochondria were reduced in Model group, and less pathological changes were found in MT group at the same time. Conclusion Melatonin can increase the expression of mtTFA and decrease the rate of mtD- NA4834bp deletion in rats with ICH. Melatonin may have neuroprotective effect to ICH by protecting mitochondria function.

关 键 词：褪黑素 脑出血 线粒体转录因子A 线粒体DNA 

分 类 号：R743.34[医药卫生—神经病学与精神病学]