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雷帕霉素对自闭症大鼠病症行为的改善作用

, PP. 420-424

Keywords: 雷帕霉素,自闭症,自噬

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Abstract:

目的探讨雷帕霉素(rapamycin)对自闭症大鼠病症行为的改善作用及相关机制。方法采用丙戊酸钠(sodiumvalproate,VPA)一次性腹腔注射孕12.5d大鼠制备自闭症幼大鼠模型,雷帕霉素处理组于VPA注射后每天给大鼠口服4mg/kg雷帕霉素直至断奶。将出生幼鼠分为4组:对照组,VPA处理组,雷帕霉素处理组与VPA联合雷帕霉素处理组。在幼鼠出生后35d进行社会交往行为检测、神经行为学检测,并分离提取脑组织蛋白通过Westernblot分析mTOR磷酸化水平及自噬标志蛋白LC3表达情况;电镜分析前额叶组织中自噬小体形成情况。结果成功制备自闭症大鼠模型。与对照相比,VPA处理组社会交往能力下降、在中央区活动时间增加、站立次数减少(P<0.05),符合自闭症行为特征;雷帕霉素单独处理组无明显行为学变化;但雷帕霉素联合处理能明显改善VPA处理导致的自闭症行为症状(P<0.05)。Westernblot结果显示,与对照组相比,VPA处理可增强大鼠前额叶、海马及小脑组织中mTOR磷酸化水平,并降低LC3-Ⅱ表达水平;而雷帕霉素联合处理则能抑制上述脑组织中mTOR的磷酸化并增强LC3-Ⅱ表达水平。电镜分析结果表明,VPA处理可减少幼鼠前额叶组织中的自噬小体,而雷帕霉素联合处理则能明显增加自噬小体的形成。结论雷帕霉素可改善自闭症模型大鼠的病症行为,机制可能与抑制mTOR活性并增强细胞自噬相关。

References

[1]  Napoli E,Duenas N,Giulivi C. Potential therapeutic use of the ketogenic diet in autism spectrum disorders[J]. Front Pediatr,2014,2:69.? [2]陈文雄. 孤独症70年:从Kanner到DSM-V [J]. 临床儿科杂志,2013,31(11): 1001-1004.? [3]Matson J L,Jang J. Treating aggression in persons with autism spectrum disorders:A review [J]. Res Dev Disabil,2014,35(12):3386-3391. [4]Tsai P T,Hull C,Chu Y, et al. Autistic-like behaviour and cerebellar dysfunction in Purkinje cell Tsc1 mutant mice [J]. Nature,2012,488(7413):647-651.? [5]Zhu L,Yang T,Li L, et al. TSC1 controls macrophage polarization to prevent inflammatory disease [J]. Nat Commun,2014,5: 4696.? [6]Schneider T,Przewlocki R. Behavioral alterations in rats prenatally exposed to valproic acid:animal model of autism [J]. Neuropsychopharmacology,2005,30(1):80-89.? [7]Banerjee S,Riordan M,Bhat M A. Genetic aspects of autism spectrum disorders:insights from animal models [J]. Front Cell Neurosci,2014, 8:58.? [8]Shah C R,Forsberg C G,Kang J Q, et al. Letting a typical mouse judge whether mouse social interactions are atypical [J]. Autism Res,2013,6(3):212-220.? [9]Takei N,Nawa H. mTOR signaling and its roles in normal and abnormal brain development [J]. Front Mol Neurosci,2014,7:28. [10]Liu F,Zhang H,Zhang K, et al. Rapamycin promotes Schwann cell migration and nerve growth factor secretion[J].Neural Regen Res,2014,9(6):602-609.? [11]El-Chemaly S,Goldberg H J,Glanville A R. Should mammalian target of rapamycin inhibitors be stopped in women with lymphangioleiomyomatosis awaiting lung transplantation? [J]. Expert Rev Respir Med,2014,8(6): 657-660.? [12]Chen W,Sun Y,Liu K, et al. Autophagy:a double-edged sword for neuronal survival after cerebral ischemia [J]. Neural Regen Res,2014,9(12):1210-1216.? [13]Kesidou E,Lagoudaki R,Touloumi O, et al. Autophagy and neurodegenerative disorders [J]. Neural Regen Res,2013,8(24):2275-2283.? [14]Zhang Y,Yuan X,Wang Z, et al. The canonical Wnt signaling pathway in autism [J]. CNS Neurol Disord Drug Targets,2014,13(5): 765-770.
[2]  赵雪晴,赵聪敏,吴至凤,等.32例自闭症儿童的睡眠相关问题分析[J].第三军医大学学报,2009,31(22):2196.  ZHAO Xue-qing,ZHAO Cong-min,WU Zhi-feng,et al.Analysis of sleep-related problems in 32 autistic children[J].J Third Mil Med Univ,2009,31(05):2196.

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