白藜芦醇对孤独症大鼠病症行为的改善作用  

Resveratrol improves autistic behaviors in rat model

作　　者：戴旭芳[1,2] 秦利燕[3] 连继勤[4] 

机构地区：[1]重庆师范大学教育科学学院重庆市特殊儿童心理诊断与教育技术重点实验室,重庆400047 [2]重庆师范大学教育科学学院特殊教育系,重庆400047 [3]第三军医大学西南医院输血科,重庆400038 [4]第三军医大学基础医学部生物化学与分子生物学教研室,重庆400038

出　　处：《第三军医大学学报》2017年第13期1360-1365,共6页Journal of Third Military Medical University

基　　金：国家自然科学基金青年科学基金(31201068)~~

摘　　要：目的探讨白藜芦醇(resveratrol)改善孤独症大鼠病症行为的作用及可能机制。方法于大鼠孕12.5 d丙戊酸钠(sodium valproate,VPA)腹腔一次性注射制备孤独症幼鼠模型。白藜芦醇处理组从母鼠怀孕后第6天开始按照3.6 mg/kg体质量在孕鼠皮下注射白藜芦醇,持续注射13 d。将幼鼠分为4组:对照组、白藜芦醇处理组、VPA处理组、VPA联合白藜芦醇处理组,每组3只。出生后35 d对幼鼠进行重复行为、神经行为与社会交往行为检测,通过Western blot检测脑组织中自噬标志蛋白LC3及SIRT1表达变化。结果成功获得孤独症模型大鼠。与对照组相比,VPA组重复行为增强、社会交往能力下降、中央区活动时间与距离增加、站立次数减少(P<0.05),符合孤独症行为特征;白藜芦醇组无明显行为学变化;但白藜芦醇联合处理可显著改善VPA处理引起的孤独症行为症状(P<0.05),包括重复行为减弱,社会交往能力增强,中央区活动时间与距离减少、站立次数增加。Western blot检测结果显示,与对照组相比,VPA处理可降低大鼠脑组织中SIRT1表达,并抑制LC3-Ⅱ表达水平;而白藜芦醇联合处理则可增强大脑组织中SIRT1与LC3-Ⅱ的表达。结论白藜芦醇能改善孤独症模型大鼠的病症行为,机制可能与增强细胞自噬及SIRT1表达相关。Objective To determine the effect of resveratrol on the behaviors of autistic rats and investigate the possible mechanism. Methods Rat model of autism was inflicted by intraperitoneal injection of sodium valproate （VPA） in rats after pregnancy for 12.5 d. The pregnant rats of the resveratrol group were treated with resveratrol via subcutaneous injection at a dose of 3.6 mg/kg per day from E6 to El8. Then the offspring were randomly divided to 4 groups： control, VPA treatment, resveratrol treatment, and VPA ＋ resveratrol treatment groups （n = 3 for each group）. The repetitive behavior, neural behavior and social interaction were evaluated in the young rats in 35 d after born. The expression levels of LC3- Ⅱ and SIRT1 in brain tissues were detected by Western blotting. Results The rat model of autism was established successfully. Compared to the control rats, the rats treated with VPA showed excessive repetitive behavior, lower social interaction, longer moving time and distance in central area, and reduced standing times （P 〈0. 05 ）, which were in accordance with the typical behaviors of autistic rats. Treatment with resveratrol alone resulted in no obvious changes in the social interaction and neural behavior in the young rats, but resveratrol treatment corrected the VPA-induced autistic-like behaviors （P 〈 0.05 ）. Western blotting indicated that VPA treatment reduced the levels of SIRT1 and LC3- Ⅱ in the brain tissues including prefrontal lobe, seahorse and cerebellum. However, resveratrol attenuated VPA-triggered down-regulation of SIRT1 and LC3-Ⅱ. Conclusion Resveratrol may correct the behaviors of autistic rats through SIRT1 enhancement mediated autophagy up-regulation.

关 键 词：白藜芦醇 孤独症 自噬 SIRT1 

分 类 号：R-332[医药卫生] R285.6