欢迎访问《解剖学报》官方网站！今天是
English
孤独症大鼠海马自噬相关蛋白的表达
Expression of the autophagy-related protein in hippocampus in a rat model of autism
目的 探讨细胞自噬在孤独症发病中的作用。 方法 健康繁殖期Wistar雌鼠20只(250～260g)，雄鼠10只(280～290g)，按2∶1比例合笼过夜，次日早上阴道涂片发现精子计为孕1d。在其孕12.5d时，10只雌鼠腹腔注射丙戊酸钠，其子代为孤独症模型组；10只注射同等剂量生理盐水，其子代为正常组。通过比较自梳理实验、三箱实验验证孤独症模型是否成功；Western blotting方法对比正常组与孤独症模型组大鼠生后42d（P42）海马自噬相关蛋白LC3-Ⅱ、Beclin-1和P62表达的变化。 结果 1.成功建立孤独症动物模型,与正常组比较，自梳理实验显示, 模型组理毛时间较正常显著增加（P<0.05），三箱实验结果显示，模型组大鼠交互能力障碍、缺乏对新鲜事物的偏好性；2.与正常组相比较，模型组大鼠P42d海马自噬相关蛋白LC3-Ⅱ表达显著降低（P<0.05），Beclin 1表达显著降低（P<0.05），P62表达显著升高（P<0.05）。 结论 孤独症大鼠P42d海马自噬活性降低，提示增强自噬可能是一个潜在的治疗策略。
Objective To investigate the effect of autophagy in the rat model of autism. Methods Twenty female Wistar rats (weight 250-260g) were mated with 10 male (weight 280-290g) overnight, and in the morning when spermatozoa were found it was designated as the first day of gestation. Females received a single intraperitoneal injection of sodium valproate on the 12.5 day after conception, and control females were injected with physiological saline at the same time. The offspring of valproate-treated females were model group, and the offspring of physiological saline -treated females were control group. The self-grooming test and three-chambered social test were used to confirm whether the autism model were successful. Western blotting was used to detect the expressed level of LC3-Ⅱ, Beclin 1 and P62 in hippocampal of eatch group. Results 1.The animal model of autism was successfully established. Compared with the control group, the cumulative self-grooming time was significantly increased（P<0.05）, the sociability and preference for social novelty were significantly decreased（P<0.05）. 2. Compared with normal control group, the model group significantly decreased the expression level of LC3-Ⅱ（P＜0.05）and Beclin 1（P＜0.05）in hippocampal. Meanwhile the expression level of P62 was significantly increased（P＜0.05）. Conclusion The present findings confirmed that the autophagy is inhibitied in hippocampus of autism, which suggests modulation of autophagy might be a potential therapeutic strategy for autism.
孤独症 / 海马 / 程序性细胞死亡 / 自噬 / 免疫印迹法 / 大鼠
Autism / Hippocampus / Programmed cell death / Autophagy / Western blotting / Rat
［1］Bakhshipour A，Mahmood Aliloo M，Shahrokhi H, et al. Sequences of mind development in boys with autism spectrum disorder［J］. ISRN Neurol，2012，2012：637453.
［2］Geschwind DH. Autism: many genes, common pathways ［J］? Cell，2008，135(3)：391-395.
［3］Geschwind DH. Advances in autism［J］. Annu Rev Med，2009，60：367-380.
［4］Grabrucker AM. Environmental factors in autism［J］.Front Psychiatry，2013，3：118.
［5］Deth R，Muratore C，Benzecry J, et al. How environmental and genetic factors combine to cause autism: a redox/methylation hypothesis［J］. Neurotoxicology，2008，29(1)：190-201.
［6］Hazlett HC，Poe M，Gerig G, et al. Magnetic resonance imaging and head circumference study of brain size in autism: birth through age 2 years［J］. Arch Gen Psychiatry，2005，62(12)：1366-1376.
［7］Lainhart JE, LangeN. Increased neuron number and head size in autism［J］. JAMA，2011，306(18)：2031-2032.
［8］Fuchs Y, Steller H. Programmed cell death in animal development and disease［J］. Cell，2011，147(4)：742-758.
［9］Kim WR, Sun W. Programmed cell death during postnatal development of the rodent nervous system［J］. Dev Growth Differ，2011，53(2)：225-235.
［10］Wen M,Zhao J,Bao XX,et al.Expression of the apotosis-related protein in prefrontal cortex in a rat model of autism［J］. Journal of Shandong University（Health Sciences），2014,52(2)：48-51.(in Chinese)
文敏，赵晶，鲍星星,等. 孤独症大鼠前额叶皮质神经元凋亡相关蛋白的表达［J］. 山东大学学报（医学版），2014，52(2)：48-51.
［11］Conradt B. Genetic control of programmed cell death during animal development［J］. Annu Rev Genet，2009，43：493-523.
［12］Tsukamoto S, Kuma A, Murakami M, et al. Autophagy is essential for preimplantation development of mouse embryos［J］. Science，2008，321(5885)：117-120.
［13］Cecconi F,Levine B. The role of autophagy in mammalian development: cell makeover rather than cell death［J］. Science，2008，15(3)：344-357.
［14］Schneider T，Przewlocki R. Behavioral alterations in rats prenatally exposed to valproic acid: animal model of autism［J］. Neuropsychopharmacology，2005，30(1)：80-89.
［15］Silverman JL, Tolu SS, Barkan CL, et al. Repetitive self-grooming behavior in the BTBR mouse model of autism is blocked by the mGluR5 antagonist MPEP［J］. Neuropsychopharmacology，2010，35(4)：976-989.
［16］Silverman JL, Yang M, Lord C, et al. Behavioural phenotyping assays for mouse models of autism［J］. Nat Rev Neurosci，2010，11(7)：490-502.
［17］Moy SS, Nonneman RJ, Young NB, et al. Impaired sociability and cognitive function in Nrcam-null mice［J］. Behav Brain Res，2009，205(1)：123-131.
［18］Mizushima N, Levine B, Cuervo AM，et al. Autophagy fights disease through cellular self-digestion［J］. Nature, 2008, 451(7182)：1069-1075.
［19］Berry DL, Baehrecke EH. Autophagy functions in programmed cell death［J］. Autophagy，2008，4(3)：359-360.
［20］Hale AN, Ledbetter DJ, Gawriluk TR, et al. Autophagy: regulation and role in development［J］. Autophagy，2013，9(7)：951-972.
［21］Kabeya Y, Mizushima N, Ueno T, et al. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing［J］. EMBO J, 2000, 19(21)： 5720-5728.
［22］Zhao MM,Li R,Du LJ,et al.Expression and significance of autophagy-related proteins LC-3 and Beclin-1 in silicosis occurrence in rats［J］. Acta Anatomica Sinica，2013，44(3)：403-408. (in Chinese)
赵曼曼，李冉，都凌杰,等. 自噬相关蛋白LC-3和Beclin-1在大鼠硅沉着病发生中的表达及意义［J］. 解剖学报，2013，44(3)：403-408.
［23］Sun Q, Fan W, Zhong Q. Regulation of Beclin 1 in autophagy［J］. Autophagy, 2009, 5(5)：713-716.
［24］Komatsu M. Potential role of p62 in tumor development［J］. Autophagy，2011，7(9)：1088-1090.
［25］Shen W, Ganetzky B. Autophagy promotes synapse development in drosophila［J］. J Cell Biol，2009，187(1)：71-79.
贵州省高层次人才科研条件项目;贵州省科技厅项目
/
| 〈 |
|
〉 |
