姜黄素早期干预对孤独症模型鼠海马神经元和星形胶质细胞的影响

Effects of early intervention of curcumin on hippocampal neurons and astrocytes in autistic model rats

目的:研究孤独症模型鼠海马神经元和星形胶质细胞的变化以及姜黄素早期干预对二者表达的影响。方法:根据Schneider的方法,对孕12.5天Wistar大鼠腹腔注射丙戊酸钠600mg/kg建立子代孤独症模型,正常组注射同等剂量的生理盐水(正常组),分别对两组仔鼠进行模型鉴定。随机选取7日龄模型仔鼠20只,正常组仔鼠10只。模型组仔鼠随机分为模型组10只和姜黄素组10只。姜黄素组于7日龄连续3周腹腔注射姜黄素50mg/kg[姜黄素用含1ml/L二甲基亚砜(dimethyl sulfoxide,DMSO)的PBS液配成10g/L的溶液],正常组、模型组于7日龄连续三周腹腔注射同等剂量的含1ml/L DMSO的PBS液。利用尼氏染色、免疫荧光染色观察比较28日龄三组仔鼠海马神经元和星形胶质细胞的形态和数量。结果:发育方面:与正常组相比,模型组体重明显降低;行为学方面:模型组社会交往和交流次数减少,重复性刻板行为增加,并且学习记忆能力下降;尼氏染色:正常组神经元排列紧密规则,面积大小无明显差别,数量较多;模型组神经元排列稀疏且不规则,面积较小,数量减少;姜黄素组神经元排列较规则,数量有所增加;免疫荧光染色:姜黄素干预后神经元数量增加(P<0.05),星形胶质细胞数量降低(P<0.05)。结论:孤独症模型仔鼠海马神经元和星形胶质细胞表达异常;姜黄素早期干预后上调了神经元的表达,抑制了星形胶质细胞的表达。

Objective:To study the changes of hippocampal neurons and astrocytes in autism model rats and the effect of early curcumin intervention on their expression.Method:According to Schneider’s method,Wistar rats 12.5 days gestation were intraperitoneally injected with sodium valproate 600 mg/kg to establish a progeny autism model.The normal group was injected with the same dose of normal saline(normal group).The two groups of rats were identified by model.27-day-old model rats were randomly selected,and 10 normal rats were selected.Model rats were randomly divided into model groups(n=10)and curcumin groups(n=10).Curcumin groups were injected intraperitoneally with curcumin 50 mg/kg at 7 days of age for 3 weeks[Curcumin was mixed with PBS containing 1 ml/L dimethyl sulfoxide(DMSO)to make a 10 g/L solution].In the normal group and model group,the same dose of PBS solution containing 1 ml/L DMSO were injected intraperitoneally at 7 days of age for three consecutive weeks.The morphology and number of hippocampal neurons and astrocytes in three groups of 28-day-old rats were observed and compared using Nissl staining and immunofluorescence staining.Result:Development:compared with the normal group,the model group had a significant weight loss.Behavioral aspects:The model group had fewer social interactions and exchanges,increased repetitive stereotyped behavior,and decreased learning and memory abilities.Nissl staining:the arrangement of neurons in the normal group is close and regular,and there is no obvious difference in area size,and the number is increased.The neurons in the model group are sparsely and irregularly arranged,and the area is small with reduced number.The neurons in the curcumin group are arranged regularly,and the number is increased.Immunofluorescence staining:after curcumin intervention,the number of neurons increased(P<0.05),and the number of astrocytes decreased(P<0.05).Conclusion:The expression of neurons and astrocytes in hippocampus of autism model is abnormal,curcumin upregulates the expression of neurons after early intervention and inhibits the expression of astrocytes.