白藜芦醇对孤独症大鼠病症行为的改善作用

戴旭芳; 秦利燕; 连继勤

doi:10.16016/j.1000-5404.201703153

您当前的位置：

首页 >

文章列表页 >

白藜芦醇对孤独症大鼠病症行为的改善作用

基础医学 | 更新时间：2026-01-09

- 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
- 第三军医大学学报 2017年39卷第13期页码：1360-1365
- 作者机构：
  
  1.400047 重庆，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
  2.400047 重庆，重庆师范大学教育科学学院, 特殊教育系
  3.400038 重庆，第三军医大学, 西南医院输血科
  4.400038 重庆，第三军医大学, 基础医学部生物化学与分子生物学教研室
- 作者简介：
  
  [ 戴旭芳，E-mail：xufangd@aliyun.com DAI Xufang, E-mail: xufangd@aliyun.com
- 基金信息：
  
  国家自然科学基金青年科学基金(31201068)
- DOI：10.16016/j.1000-5404.201703153
  中图分类号： R-332;R285.6;R749.94
- 收稿：2017-03-24，
  
  修回：2017-04-16，
  
  纸质出版：2017-07-15
- 稿件说明：
移动端阅览
戴旭芳, 秦利燕, 连继勤. 白藜芦醇对孤独症大鼠病症行为的改善作用[J]. 第三军医大学学报, 2017,39(13):1360-1365.

Xufang DAI, Liyan QIN, Jiqin LIAN. Resveratrol improves autistic behaviors in rat model[J]. Journal of Third Military Medical University, 2017, 39(13): 1360-1365.
戴旭芳, 秦利燕, 连继勤. 白藜芦醇对孤独症大鼠病症行为的改善作用[J]. 第三军医大学学报, 2017,39(13):1360-1365. DOI： 10.16016/j.1000-5404.201703153.

Xufang DAI, Liyan QIN, Jiqin LIAN. Resveratrol improves autistic behaviors in rat model[J]. Journal of Third Military Medical University, 2017, 39(13): 1360-1365. DOI： 10.16016/j.1000-5404.201703153.

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(

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(

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。

Abstract

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 E18. Then the offspring were randomly divided to 4 groups: control

VPA treatment

resveratrol treatment

and VPA+resveratrol treatment groups (

=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 (

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 (

0.05). Western blotting indicated that VPA treatment reduced the levels of SIRT1and LC3-Ⅱin 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

Keywords

references

NAPOLI E, DUENAS N, GIULIVI C. Potential therapeutic use of the ketogenic diet in autism spectrum disorders[J]. Front Pediatr, 2014, 2: 69. DOI: 10.3389/fped.2014.00069.

陈文雄.孤独症70年:从Kanner到DSM-Ⅴ[J].临床儿科杂志, 2013, 31(11): 1001-1004. DOI:10.3969/j.issn.1000-3606.2013.11.001.

CHEN W X. Seventy years autism:From kanner to dsm-v[J]. Journal of Clinical Pediatrics, 2013, 31(11): 1001-1004. 1111111155555555

MATSON J L, JANG J. Treating aggression in persons with autism spectrum disorders: a review[J]. Res Dev Disabil, 2014, 35(12): 3386-3391. DOI:10.1016/j.ridd.2014.08.025.

TANG G, GUDSNUK K, KUO S H, , et al. Loss of mTOR-dependent macroautophagy causes autistic-like synaptic pruning deficits[J]. Neuron, 2014, 83(5): 1131-1143. DOI:10.1016/j.neuron.2014.07.040.

SAHIN M. Targeted treatment trials for tuberous sclerosis and autism: no longer a dream[J]. Curr Opin Neurobiol, 2012, 22(5): 895-901. DOI:10.1016/j.conb.2012.04.008.

秦利燕, 戴旭芳.雷帕霉素对自闭症大鼠病症行为的改善作用[J].第三军医大学学报, 2015, 37(05):420-424. DOI:10.16016/j.1000-5404.201409094.

QIN L Y, DAI X F.Role of rapamycin in improvement of autistic rats[J].J Third Mil Med Univ, 2015, 37(05):420-424. DOI:10.16016/j.1000-5404.201409094.

DIAZ M, DEGENS H, VANHEES L, et al. The effects of resveratrol on aging vessels[J]. Exp Gerontol, 2016, 85: 41-47. DOI:10.1016/j.exger.2016.09.016.

张勇, 陈明亮, 高燕翔, 等.白藜芦醇通过诱导自噬缓解肝细胞脂肪变性[J].第三军医大学学报, 2014, 36(21):2178-2182.

ZHANG Y, CHEN M L, GAO Y X, et al.Resveratrol attenuates steatosis in cultured hepatic cells by inducing autophagy[J].J Third Mil Med Univ, 2014, 36(21):2178-2182.

邓皓月, 糜漫天.白藜芦醇通过上调SIRT1/自噬通路改善Aβ25-35对PC12细胞增殖的抑制作用[J].第三军医大学学报, 2016, 38(06):619-622. DOI:10.16016/j.1000-5404. 201507141.

DENG H Y, MI M T.Resveratrol attenuates Aβ25-35 induced neurotoxicity via activation of SIRT1/autophagy signaling pathway[J].J Third Mil Med Univ, 2016, 38(06):619-622. 1111111155555555

CAPUTO M, MATARESE G, PIERANTONI G M, et al. Convergent effects of resveratrol and PYK2 on prostate cells[J]. Int J Mol Sci, 2016, 17(9): E1542. DOI: 10.3390/ijms17091542.

SCHNEIDER T, PRZEWŁOCKI R. Behavioral alterations in rats prenatally exposed to valproic acid: animal model of autism[J]. Neuropsychopharmacology, 2005, 30(1): 80-89. DOI:10.1038/sj.npp.1300518.

BORRIELLO A, BENCIVENGA D, CALDARELLI I, et al. Resveratrol: from basic studies to bedside[J]. Cancer Treat Res, 2014, 159: 167-184. DOI:10.1007/978-3-642-38007-5_10.

CHEN W, SUN Y, LIU K, et al. Autophagy: a double-edged sword for neuronal survival after cerebral ischemia[J]. Neural Regen Res, 2014, 9(12): 1210-1216. DOI:10.4103/1673-5374.135329.

DERE E, DAHM L, LU D, et al. Heterozygous ambra1 deficiency in mice: a genetic trait with autism-like behavior restricted to the female gender[J]. Front Behav Neurosci. 2014, 16(8):181. DOI: 10.3389/fnbeh.2014.00181.

POULTNEY C S, GOLDBERG A P, DRAPEAU E, et al. Identification of small exonic CNV from whole-exome sequence data and application to autism spectrum disorder[J]. Am J Hum Genet, 2013, 93(4): 607-619. DOI:10.1016/j.ajhg.2013.09.001.

WANG R, LIU Y Y, LIU X Y, et al. Resveratrol protects neurons and the myocardium by reducing oxidative stress and ameliorating mitochondria damage in a cerebral ischemia rat model[J]. Cell Physiol Biochem, 2014, 34(3): 854-864. DOI:10.1159/000366304.

LIU S, LI T, LIU H, et al. Resveratrol exerts antidepressant properties in the chronic unpredictable mild stress model through the regulation of oxidative stress and mTOR pathway in the rat hippocampus and prefrontal cortex[J]. Behav Brain Res, 2016, 302: 191-199. DOI:10.1016/j.bbr.2016.01.037.

LIN C J, CHEN T H, YANG L Y, et al. Resveratrol protects astrocytes against traumatic brain injury through inhibiting apoptotic and autophagic cell death[J]. Cell Death Dis, 2014, 5: e1147. DOI:10.1038/cddis.2014.123.

WANG F, CUI N, YANG L, et al. Resveratrol rescues the impairments of hippocampal neurons stimulated by microglial over-activation in vitro [J ] . Cell Mol Neurobiol, 2015, 35(7): 1003-1015. DOI:10.1007/s10571-015-0195-5.

APPUHAMY J A, NAYANANJALIE W A, ENGLAND E M, et al. Effects of AMP-activated protein kinase (AMPK) signaling and essential amino acids on mammalian target of rapamycin (mTOR) signaling and protein synthesis rates in mammary cells[J]. J Dairy Sci, 2014, 97(1): 419-429. DOI:10.3168/jds.2013-7189.

NG F, TANG B L. Sirtuins'modulation of autophagy[J]. J Cell Physiol, 2013, 228(12): 2262-2270. DOI:10.1002/jcp.24399.

张应花, 杨彩玲, 崔卫刚, 等.舒林酸对丙戊酸孤独症动物模型大鼠氧化应激变化的影响[J].中国病理生理杂志, 2014, 30(12): 2161-2165. DOI:10.3969/j.issn.1000-4718. 2014.12.008.

ZHANG Y H, YANG C L, CUI W G, et al. Effects of sulindac on oxidative stress in an autistic model induced by pre-natal exposure to valproic acid[J]. Chinese Journal of Pathophysiology, 2014, 30(12): 2161-2165. DOI:10.3969/j.issn.1000-4718.2014.12.008.

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

白藜芦醇通过上调SIRT1/自噬通路改善Aβ_25-35对PC12细胞增殖的抑制作用

白藜芦醇通过诱导自噬缓解肝细胞脂肪变性

Sirt1通过调控髓核细胞组蛋白H3K18乳酸化参与椎间盘退变的机制研究

RANKL通过ROS介导HIF-1α下调促进自噬和破骨细胞分化

转录因子EB增强巨噬细胞自噬功能及逆转内毒素耐受的作用