α-硫辛酸对高脂饮食肥胖小鼠术后空间学习记忆功能的影响
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摘要
目的观察α-硫辛酸(α-LA)对高脂饮食(HFD)肥胖小鼠术后空间学习记忆功能的影响并探讨可能的机制。方法 120只雄性C57BL/6小鼠被分为6组(对照组,对照+手术组,对照+α-LA+手术组,HFD组,HFD+手术组,HFD+α-LA+手术组),每组20只。HFD干预组给予高脂饮食喂养12周,α-LA干预组给予α-LA灌胃12周,肝部分切除术后第1～5天行水迷宫。检测小鼠体质量,免疫荧光法检测海马casepase 3、Bcl-2表达情况,透射电镜观察海马神经元及突触结构。结果 HFD组比对照组体质量明显增加,HFD+手术组比对照+手术组体质量明显增加,HFD+α-LA+手术组术后空间学习记忆能力明显强于HFD+手术组(P<0. 01)。HFD+α-LA+手术组术后第5天casepase 3、Bcl-2表达明显低于HFD+手术组,神经元及突触结构与HFD+手术组相比差异有统计学意义(P<0. 01)。结论α-LA缓解了高脂饮食诱导的肥胖小鼠术后空间学习记忆功能下降程度,可能与抑制海马神经元凋亡,维持突触正常结构有关。
Objective To investigate the effect of alpha-lipoic acid(α-LA) on postoperative spatial learning and memory function of obese mice administered with high-fat diet(HFD).Methods A total of 120 male C57BL/6 mice were divided into six groups which received HFD or normal diet for 12 weeks. α-LA treatment group were administed with α-LA for 12 weeks. The cognitive function was assessed with Morris water maze. The expressions of casepase 3,Bcl-2 were detected by immunofluorescence. The ultrastructure of hippocampal neurons and synapses were observed by transmission electron microscope. Results The weight in HFD treatment group was higher than that in control group,and the weight in HFD + operation group was higher than that in control+operation group. α-LA treatment repaired the impaired cognitive function of mice administed with HFD. The expression levels of casepase 3,Bcl-2 were higher in HFD + operation group than those in HFD+α-LA+operation group. In HFD + operation group,the number of neurons and synaptic were lower and the structure was damaged more significantly compared with HFD + α-LA + operation group. Conclusions α-LA may relieve the degree of postoperative learning and memory impairment in obese mice induced by HFD by inhibiting the apotosis of hippocampal neuron and maintaining the nomal structure of synapsis.
Objective To investigate the effect of alpha-lipoic acid(α-LA) on postoperative spatial learning and memory function of obese mice administered with high-fat diet(HFD).Methods A total of 120 male C57BL/6 mice were divided into six groups which received HFD or normal diet for 12 weeks. α-LA treatment group were administed with α-LA for 12 weeks. The cognitive function was assessed with Morris water maze. The expressions of casepase 3,Bcl-2 were detected by immunofluorescence. The ultrastructure of hippocampal neurons and synapses were observed by transmission electron microscope. Results The weight in HFD treatment group was higher than that in control group,and the weight in HFD + operation group was higher than that in control+operation group. α-LA treatment repaired the impaired cognitive function of mice administed with HFD. The expression levels of casepase 3,Bcl-2 were higher in HFD + operation group than those in HFD+α-LA+operation group. In HFD + operation group,the number of neurons and synaptic were lower and the structure was damaged more significantly compared with HFD + α-LA + operation group. Conclusions α-LA may relieve the degree of postoperative learning and memory impairment in obese mice induced by HFD by inhibiting the apotosis of hippocampal neuron and maintaining the nomal structure of synapsis.
引文
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[2] Ghibu S,Richard C,Delemasure S,et al. An endogenous dithiol with antioxidant properties:alpha-lipoic acid,potential uses in caridovascular diseases[J]. Ann Cardiol Angeiol(Paris),2008,57(3):161-165.
[3] Abdin AA,Sarhan NI. Intervention of mitochondrial dysfunction-oxidative-dependent apoptosis as a possible neuroprotective mechanism ofα-lipoic acid against rotenoneinduced Parkinsonism and L-dopa toxicity[J].Neurosci Res,2011,71(4):387-395.
[4] Jansen L,Hoffmeister M,Chang-Claude J,et al. Agespecific administration of chemotherapy and long-term quality of life in stageⅡandⅢcolorectal cancer patients:A population-based prospective cohort[J]. Oncologist,2011,16(12):1741-1751.
[5] Jansen L,Koch L,Brenner H,et al. Quality of life among long-term(≥5 years)colorectal cancer survivors-systematic review[J]. Eur J Cancer,2010,46(7):2879-2888.
[6] Biancotto A,Wank A,Perl S,et al. Baseline levels and temporal stability of 27 multiplexed serum cytokine concentrations in healthy subjects[J]. PLoS One, 2013, 8(12):e76091.
[7] Li YC,Xi CH,An YF,et al. Perioperative inflammatory response and protein S-100b concentrations-relationship with post-operative cognitive dysfunction in elderly patients[J].Acta Anaesthesiol Scand,2012,56(5):595-600.
[8]张昌盛,徐志鹏,米卫东.术后认知功能障碍的临床与基础研究进展[J].北京医学,2016,38(4):342-345.
[9]刘琼珍,吕文婷,蔡旻煊,等.代谢性疾病对情绪和认知功能的影响及其可能机制研究进展[J].中国药理学与毒理学杂志,2015,29(5):847-858.
[10] Rochette L,Ghibu S,Richard C. Direct and indirect antioxidant properties ofα-lipoic acid and therapeutic potential[J]. Mol Nutr Food Res, 2013, 57(1):114-125.
[11] Deng C,Sun Z,Tong G,et al.α-Lipoic acid reduces infarct size and preserves cardiac function in rat myocardial ischemia/reperfusion injury through activation of PI3K/Akt/Nrf2pathway[J]. PLoS One,2013,8(3):e58371.
[12] Mourek J,Langmeier M,Pokorny J. Significance of the plasma membrane for the nerve cell function,development and plasticity[J]. Neuro Endocrinol Lett,2009,30(6):694-699.
[13] Yang W,Shi L,Chen L,et al. Protective effects of perindopril on d-galactose and aluminum trichloride induced neurotoxicity via the apoptosis of mitochondria-mediated intrinsic pathway in the hippocampus of mice[J]. Brain Res Bull,2014,109(10):46-53.
[14] Ye LJ,Xu XH,Wang YM,et al. The efects of enriched environment on structural modification of synaptic interface and PSD-95 mRNA of rats after transient focal cerebral ischemia(in Chinese)[J]. Acta Psychologica Sinica,2008,40(6):709-716.