关键词: 孤独症, 小胶质细胞, 白介素-1β, 白介素-6, 阿魏酸

Abstract: Objective To investigate the effects of ferulic acid on behavior, activation of microglia in hippocampus and expression of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in autistic model rats, in order to explore a new approach for ASD drug therapy. Methods The autism model was prepared by referring to the Schneider autism model rat method. Forty 7-day-old model rats were randomly divided into valproate(VPA) group and ferulic acid (FA) group. Control rats 20 were randomly selected into NS group. FA group was intraperitoneally injected with ferulic acid 50mg/kg for 21 consecutive days from the 7th day, VPA group and NS group were injected with normal saline. The model was identified by developmental and behavioral tests. After the intervention, the morphological changes of hippocampus were observed by HE staining, the expression levels of IBA-1 were detected by immunofluorescence staining, and the expression levels of IL-1β, IL-6 and TNF-α were detected by enzyme-linked immunosorbent assay. Results Compared with NS group, VPA group had lower body weight, curvy tail or short tail, decreased "sociability" and "social novelty", decreased ability to distinguish social odor, and increased repetitive and stereotypical behavior (P<0.05). The nerve cells in the hippocampus were arranged in disorder, with large space, unclear structure, cell degeneration and inflammatory cell infiltration. The number of activated microglia in hippocampus increased, and the expression levels of IL-1β, IL-6 and TNF-α increased (P < 0.05). After ferulic acid intervention, the pathological damage of hippocampus in FA group was improved compared with VPA group. The number of IBA-1 positive cells and the expression levels of IL-1β and IL-6 decreased (P < 0.05). Conclusion The intervention of ferulic acid can improve the learning and memory ability of the autism model mice, and improve the abnormal development and behavioral performance of the autism model mice to a certain extent, such as impairment of social interaction. Ferulic acid can reduce the number of activated microglia and the expression levels of pro-inflammatory cytokines IL-1β and IL-6 in the hippocampus of autism model rats, thus playing a neuroprotective role.

Key words: autism, microglia cells, interleukin-1β, interleukin-6, ferulic