α-硫辛酸改善高脂饮食肥胖小鼠术后认知功能的机制探讨
|
摘要
目的观察α-硫辛酸(α-LA)对高脂饮食肥胖小鼠术后认知功能的影响并探索其可能的机制。方法 120只雄性C57BL/6小鼠被随机分为6组:对照组(C组)、高脂饮食组(H组)、手术对照组(CO组)、高脂饮食手术组(HO组)、CO+α-LA干预组和HO+α-LA干预组,每组20只。对照组给予普通饲料喂养,高脂饮食组给予高脂饮食喂养12周,α-LA干预组给予α-LA 100 mg/(kg·d)灌胃12周。术后第1～5天行水迷宫实验。术前测量小鼠体质量,检测血清总胆固醇(TC)、甘油三脂(TG)、瘦素水平,术后western blot法检测海马细胞周期依赖性蛋白激酶5(Cdk5)、P-tau、β-淀粉样蛋白(Aβ) 1-42、脑源性神经营养因子(BDNF)的表达水平。结果 H组比C组,HO组比CO组的体质量、血清TC、TG、瘦素水平明显升高,HO+α-LA组体质量、血清TC、TG、瘦素水平明显低于HO组,HO+α-LA组术后空间学习记忆能力明显强于HO组。HO+α-LA组术后第5天海马P-tau、Aβ1-42、Cdk5表达水平明显低于HO组,BDNF水平明显高于HO组。结论α-LA缓解了高脂饮食诱导的肥胖小鼠术后认知功能下降程度,可能与降低海马Cdk5、P-tau、Aβ1-42表达,上调海马BDNF表达有关。
Objective To investigate the effects and mechanism of α-LA on postoperative cognitive function( POCD) of obese mice administered with high-fat diet. Methods A total of 120 male C57 BL/6 mice were devided into 6 groups which received high-fat diet or normal diet for 12 weeks.α-LA treatment group were administered with α-LA 100 mg/( kg·d) for 12 weeks. Cognitive function was assessed using Morris water maze. The serum concentrations of total cholesterol( TC),triglyceride( TG) and leptin in serum were measured. The expressions of P-tau,β-amyloid peptide 1-42( Aβ1-42),cyclin-depended kinase5( Cdk5),brain-derived neurotrophic factor( BDNF) in hippocampus were detected by western blot. Results The weight and the concentration of TC,TG and leptin of high fat diet treatment group were higher than those of normal diet group. α-LA treatment repaired the cognitive dysfunction of mice administered with high fat diet. The expressions of Cdk5,P-tau,Aβ1-42 were higher and the BDNF level were lower in high-fat diet and operation( HO) group than those of HO+α-LA group.Conclusions α-LA could be a possible efficient target to treat postoperative cognitive dysfunction of obese mice induced by high-fat diet via the regulation of the expression levels of Cdk5,P-tau,Aβ1-42 and BDNF in hippocampus.
Objective To investigate the effects and mechanism of α-LA on postoperative cognitive function( POCD) of obese mice administered with high-fat diet. Methods A total of 120 male C57 BL/6 mice were devided into 6 groups which received high-fat diet or normal diet for 12 weeks.α-LA treatment group were administered with α-LA 100 mg/( kg·d) for 12 weeks. Cognitive function was assessed using Morris water maze. The serum concentrations of total cholesterol( TC),triglyceride( TG) and leptin in serum were measured. The expressions of P-tau,β-amyloid peptide 1-42( Aβ1-42),cyclin-depended kinase5( Cdk5),brain-derived neurotrophic factor( BDNF) in hippocampus were detected by western blot. Results The weight and the concentration of TC,TG and leptin of high fat diet treatment group were higher than those of normal diet group. α-LA treatment repaired the cognitive dysfunction of mice administered with high fat diet. The expressions of Cdk5,P-tau,Aβ1-42 were higher and the BDNF level were lower in high-fat diet and operation( HO) group than those of HO+α-LA group.Conclusions α-LA could be a possible efficient target to treat postoperative cognitive dysfunction of obese mice induced by high-fat diet via the regulation of the expression levels of Cdk5,P-tau,Aβ1-42 and BDNF in hippocampus.
引文
[1]Kelli HM,Kassas I,Lattouf OM.Cardio metabolic syndrome:a global epidemic[J].Diabetes Metab,2015,6(3):1000513.
[2]Ghibu S,Richard C,Delemasure.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 A,Sarhan N.Intervention of mitochondrial dysfunction-oxidative-dependent apoptosis as a possible neuroprotective mechanism ofα-lipoic acid against rotenone-induced Parkinsonism and L-dopa toxicity[J].Neurosci Res,2011,71(4):387-395.
[4]Higgins GM,Anderson RM.Experimental pathology of the liver.I.Restoration of the liver of the white rat following partial surgical removal[J].Arch Pathol,1931,12:186-202.
[5]张媛,斯妍娜,吕云落,等.星状神经节阻滞对老年冠状动脉旁路移植术认知功能的影响[J].实用老年医学,2013,27(10):853-855.
[6]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.
[7]Shupp A,Casimiro MC,Pestell RG.Biological functions of CDK5 and potential CDK5 targeted clinical treatments[J].Oncotarget,2017,8(10):17373-17382.
[8]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.
[9]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.
[10]Funk JA,Odejinmi S,Schnellmann RG,et al.SRT1720 induces mitochondrial biogenesis and rescues mitochondrial function after oxidant injury in renal proximal tubule cells[J].J Pharmacol Exp Ther,2010,333(2):593-601.
[11]Chen WL,Kang CH,Wang SG.α-Lipoic acid regulates lipid metabolism through induction of sirtuin 1(SIRT1)and activation of AMP-activated protein kinase[J].Diabetologia,2012,55(6):1824-1835.
[12]Liu Y,Fu X,Lan N,et al.Luteolin protects against high fat diet-induced cognitive deficits in obesity mice[J].Behav Brain Res,2014,267:178-188.
[2]Ghibu S,Richard C,Delemasure.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 A,Sarhan N.Intervention of mitochondrial dysfunction-oxidative-dependent apoptosis as a possible neuroprotective mechanism ofα-lipoic acid against rotenone-induced Parkinsonism and L-dopa toxicity[J].Neurosci Res,2011,71(4):387-395.
[4]Higgins GM,Anderson RM.Experimental pathology of the liver.I.Restoration of the liver of the white rat following partial surgical removal[J].Arch Pathol,1931,12:186-202.
[5]张媛,斯妍娜,吕云落,等.星状神经节阻滞对老年冠状动脉旁路移植术认知功能的影响[J].实用老年医学,2013,27(10):853-855.
[6]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.
[7]Shupp A,Casimiro MC,Pestell RG.Biological functions of CDK5 and potential CDK5 targeted clinical treatments[J].Oncotarget,2017,8(10):17373-17382.
[8]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.
[9]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.
[10]Funk JA,Odejinmi S,Schnellmann RG,et al.SRT1720 induces mitochondrial biogenesis and rescues mitochondrial function after oxidant injury in renal proximal tubule cells[J].J Pharmacol Exp Ther,2010,333(2):593-601.
[11]Chen WL,Kang CH,Wang SG.α-Lipoic acid regulates lipid metabolism through induction of sirtuin 1(SIRT1)and activation of AMP-activated protein kinase[J].Diabetologia,2012,55(6):1824-1835.
[12]Liu Y,Fu X,Lan N,et al.Luteolin protects against high fat diet-induced cognitive deficits in obesity mice[J].Behav Brain Res,2014,267:178-188.