LPS诱发sAPP-α转基因鼠神经细胞损伤机制的初步探讨

Neuronal injury and loss in sAPPα-Tg mice injected with LPS

目的:探讨微生物感染所造成的损伤是否与小儿孤独症的发病相关。方法:我们使用C57BL/6为背景的sAPP-α转基因小鼠和同源对照小鼠,给予低剂量(50μg)的LPS腹腔注射,于不同时间点12、24、48、72、96、120小时以及14周处死小鼠,收集相应的样本,进行不同时间点外周血细胞计数、72小时ELISA方法检测大脑内炎症因子表达水平以及14周大脑免疫细胞化学等检测。结果:实验结果表明,与同源对照小鼠比较,sAPP-α转基因幼鼠在低剂量的LPS作用下,表现为体重减轻,12、24、48、72小时外周血红细胞数和HCT降低、14周大脑海马区存在着广泛的损伤修复区,但外周血血小板计数并无明显改变。对损伤区进行进一步Nissl染色,表明损伤区为不同于任何神经细胞的一种活细胞,推测为出血损伤后的纤维细胞修复。结论:小儿孤独症患者体内高表达sAPP-α是小儿感染后引起神经系统损伤的重要因素,源于高表达于血小板上sAPP-α导致组织出血。

Objective：To research the relationship between infection and autism development.Methods：sAPPα-Tg mice and littermate controls were injected with 50 μg LPS,monitored and weighted everyday until 20 days.The mice were harvested at 12,24,48,72,96,120 h and 14 w,the blood cell was counted with coulter counter,inflammatory factors were evaluated with ELISA on day 3.The brain sections from sAPPα-Tg mice and littermate controls were reacted with Nissl or NeuN antibody and the stereological analysis was performed for NeuN-positive cells after 14 weeks.Results： Total number of red blood cells and hematocrits decreased in sAPPα-Tg mice compare with littermate control mice at 12,24,48,72 h.The counts of platelets have no obvious change.NeuN immunohistochemistry disclosed a more rarefied pattern of neurons.Furthermore,Nissl staining revealed neuronal dysmorphology suggestive of neuronal degeneration in sAPPα-Tg mice after 14 weeks.Conclusion： These data show that over-expression of sAPPα on platelets in mice leads to neuronal injury and loss that may be caused by brain hemorrhage.