探讨乙酰半胱氨酸改善大鼠杏仁核相关的自闭症及其机制

Exploring the Effect of N-Acetylcysteine on Amygdala Related Autism in Rats and Its Mechanism

摘要: 目的：探讨全身性给予乙酰半胱氨酸对于自闭症的治疗作用及其机制。方法：怀孕母鼠在怀孕的12.5天时腹腔注射一剂500 mg/kg丙戊酸。在出生第21天，给予子代公鼠进行行为测试，包括社交行为测试(SI)、开放空间行为测试(OF)、高架十字迷宫测试(EPM)。测试结束后，腹腔注射给予乙酰半胱氨酸150 mg/kg或是生理食盐水，每天一次，为期七天。七天后给予大鼠相同的行为测试。二十四小时后，处死大鼠，进行电生理纪录。结果：慢性给予丙戊酸子代乙酰半胱氨酸之后，恢复社交时间和次数以及达到缓解焦虑行为的效果。于杏仁核脑片中，丙戊酸子代有较高的mEPSCs频率和较低的PPF比值，给予NAC治疗后得以恢复。结论：给予乙酰半胱氨酸治疗之后，改善丙戊酸子代的社交障碍、过度焦虑和增强的突触前兴奋性神经传导。

Abstract: Objective: To explore the therapeutic effect and mechanism of systemic administration of N-acetylcysteine on autism. Methods: Pregnant rats were intraperitoneally injected with 500 mg/kg valproic acid at 12.5 days of pregnancy. On the 21st day of birth, the offspring male rats were given behavioral tests, including the social behavior test (SI), open field behavior test (OF), and elevated plus maze test (EPM). After the test, N-acetylcysteine 150 mg/kg or physiological salt water was injected intraperitoneally once a day for seven days. The rats were given the same behavioral test seven days later. Twenty four hours later, rats were killed and electrophysiological records were made. Results: after chronic administration of levulinic acid and N-acetylcysteine, the time and frequency of social recovery and the effect of relieving anxiety behavior were achieved. In amygdala brain slices, valproic acid progeny showed a high frequency of mEPSCs and a low PPF ratio, which recovered after treatment with NAC. Conclusions: after the treatment with acetylcysteine, the social disorder, excessive anxiety and enhanced presynaptic excitatory nerve conduction of valproate offspring can be improved.