丙戊酸钠诱导小鼠自闭症模型的改良

目的通过改良丙戊酸钠（VPA）小鼠自闭症模型，提高建模成功率，缩短实验周期，更好地模拟临床自闭症发病情况。方 法将实验小鼠分为3组，对照组在小鼠孕12.5 d时腹腔注射等体积生理盐水；传统组在小鼠孕12.5 d时一次性腹腔注射VPA 600 mg/kg；改良组在小鼠孕10、12 d时，分别腹腔注射VPA 300 mg/kg。观测3组孕鼠给药后反应和6 h死亡率、流产率、临产子 宫；观测仔鼠的形态与生长发育；观察仔鼠社会行为学，包括三腔实验、社交实验、青年玩耍实验和旷场实验等反映仔鼠自闭 症样行为。结果改良组孕鼠死亡率和流产率低于传统组（P<0.01）；与正常组相比，传统组和改良组仔鼠均存在发育障碍 （P<0.05），但是改良组新生鼠死亡率明显低于传统组，弯尾高达100%（P<0.001）。与正常组相比，改良组和传统组均出现了自 闭症样行为，即社交障碍和重复刻板行为（P<0.05）。结论改良后的给药方法，能更好的模拟人类自闭症发生的过程，同时降低 了孕鼠和新生鼠的死亡率、流产率，缩短了实验周期，提高了实验效率。

Improvement of a mouse model of valproic acid-induced autism

Objective To establish an improved mouse model of valproic acid (VPA)-induced autism that better mimics human autism. Methods We established mouse models of autism in female C57 mice by intraperitoneal injection of sodium valproate either at a single dose (600 mg/kg) on day 12.5 after conception (conventional group) or in two doses of 300 mg/kg each on days 10 and 12 after conception (modified group), and the control mice were injected with saline only on day 12.5. The responses of the mice to VPA injection, the uterus, mortality rate, and abortion rate were compared among the 3 groups. The morphology and development of the offspring mice were assessed, and their behavioral ontogeny was evaluated using 3- chambered social test, social test, juvenil play test, and open field test. Results The mortality and abortion rates were significantly lower in the modified model group than in the conventional group (P<0.01). Compared with those in the control group, the offspring mice in both the conventional group and the modified group showed developmental disorders (P<0.05). The mortality rate of the newborn mice was significantly lower in the modified group than in the conventional group with a rate of curvy tail of up to 100% (P<0.001). The offspring mice in both the modified group and conventional group exhibited autism-like behavioral abnormalities, including social disorder and repetitive stereotyped behavior (P<0.05). Conclusion The mouse model of autism established using the modified method better mimics human autism with reduced mortality and abortion rates of the pregnant mice and also decreased mortality rate of the newborn mice.