李成朋,韩飞,董智慧,罗坤,胡玉梅,官志忠,吴昌学,禹文峰
LI Chengpeng,HAN Fei,DONG Zhihui,LUO Kun,HU Yumei,GUAN Zhizhong,WU Changxue,YU Wengfeng

• 1:贵州医科大学分子生物学重点实验室
• 2:贵州医科大学地方病与少数民族疾病教育部重点实验室
• 3:贵州医科大学
• 4:贵阳中医学院基础部

摘要(Abstract)：

目的:研究α-硫辛酸(LA)对6-羟基多巴胺(6-OHDA)诱导PC12细胞损伤的保护作用。方法:体外培养PC12细胞,通过CCK-8实验筛选出诱导PC12细胞建立帕金森病(PD)细胞模型的6-OHDA最佳浓度及对PD细胞模型保护的LA最佳浓度,Western blot法检测LA预处理后对PD模型细胞中酪氨酸羟化酶(TH)表达的影响。结果:75μmol/L 6-OHDA作用于PC12细胞共培养18 h后,PC12细胞活力下降35%;而经10μmol/L LA预处理PC12细胞1 h后,再用75μmol/L 6-OHDA与PC12共培养18 h,则PC12细胞活力下降20%,提示75μmol/L 6-OHDA与10μmol/L LA为最佳处理浓度;经过LA的干预,6-OHDA诱导PC12建立的PD细胞模型中TH表达显著升高(P<0.05)。结论:LA对6-OHDA诱导的PC12细胞损伤具有保护作用。
Objective: To evaluate the neuroprotective effect of α-lipoic acid on PC12 cells induced by 6-hydroxydopamine. Methods: PC12 cells were cultured in vitro. The optimal concentration of 6-OHDA and LA for the protection of PD cell modelbv was screened out by CCK-8 experiment,and the effect of TH expression in PC12 cells was detected by Western blot. Results: The viability of PC12 cells treated with 75 μmol/L 6-OHDA for 18 h decreased by 35%. After pretreatment with 10 μmol/L LA for 1 h,and co-culture of 75 μmol/L 6-OHDA with PC12 for 18 h,the viability of PC12 cells decreased by 20%. After LA intervention,the expression of TH in PD cells induced by 6-OHDA is significantly increased by PC12( P < 0. 05). Conclusions: La has significant neuroprotective effects on 6-OHDA induced PC12 cell injury.

关键词(KeyWords)： α-硫辛酸;6-羟多巴胺;PC12细胞;酪氨酸羟化酶;帕金森病;神经保护;氧化应激
α-lipoic acid;6-hydroxydopamine;PC 12 cell;tyrosine hydroxylase;Parkinson's disease;neuroprotection;oxidative stress

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金(81360199);; 教育部科学技术研究项目(213032A);; 贵州省国际科技合作计划项目[黔科合外G字(2013)7026号];; 贵州省创新计划项目[黔教合协同创新中心(2014)06];; 贵州省教育厅项目[黔教合人才团队字(2015)63]

作者(Author): 李成朋,韩飞,董智慧,罗坤,胡玉梅,官志忠,吴昌学,禹文峰
LI Chengpeng,HAN Fei,DONG Zhihui,LUO Kun,HU Yumei,GUAN Zhizhong,WU Changxue,YU Wengfeng

DOI: 10.19367/j.cnki.1000-2707.2018.03.004

参考文献(References)：

• [1]KALIA L V,LANG A E.Parkinson's disease[J].Lancet,2015,386(96):896-912.
• [2]WIRDEFELDT K,ADAMI H O,COLE P,et al.Epidemiology and etiology of Parkinson’s disease:a review of the evidence[J].European Journal of Epidemiology,2011,26 Suppl 1(1):1-58.
• [3]SMITH A R,SHENVI S V,WIDLANSKY M,et al.Lipoic acid as a potential therapy for chronic diseases associated with oxidative stress[J].Current Medicinal Chemistry,2004,11(9):1135-1146.
• [4]AA A,NI S.Intervention of mitochondrial dysfunctionoxidative stress-dependent apoptosis as a possible neuroprotective mechanism ofα-lipoic acid against rotenone-induced parkinsonism and L-dopa toxicity[J].Neuroscience Research,2011,71(4):387-395.
• [5]GOR CA A,HUK-KOLEGA H,PIECHOTA A,et al.Lipoic acid-biological activity and therapeutic potential[J].Pharmacological Reports Pr,2011,63(4):849-858.
• [6]JALALINADOUSHAN M,ROGHANI M.Alpha-lipoic acid protects against 6-hydroxydopamine-induced neurotoxicity in a rat model of hemi-parkinsonism.[J].Brain Research,2013,1505(6):68-74.
• [7]FABIO B,MARIE THERESE A.Animal models of Parkinson’s disease[J].Febs Journal,2012,279(7):1156-1166.
• [8]汤森路透.疾病综述:帕金森病[J].国际药学研究杂志,2015(3):338-345.
• [9]LANGE A B,CHAN K.Dopaminergic control of foregut contractions in Locusta migratoria[J].Journal of Insect Physiology,2008,54(1):222-230.
• [10]杨子祯,马驰,司成庆,等.细胞程序性死亡与帕金森病的相关研究进展[J].现代生物医学进展,2015(8):1582-1584.
• [11]WIRDEFELDT K,ADAMI H,COLE P,et al.Epidemiology and etiology of Parkinson’s disease:a review of the evidence[J].European Journal of Epidemiology,2011,26(1):1.
• [12]JANKOVIC J.Parkinson's disease:clinical features and diagnosis[J].J Neurol Neurosurg Psychiatry,2008,79(4):368-376.
• [13]STANKIEWICZ J,PANTER S S,NEEMA M,et al.Iron in chronic brain disorders:imaging and neurotherapeutic implications[J].Neurotherapeutics the Journal of the American Society for Experimental Neurotherapeutics,2007,4(3):371-386.
• [14]LIU J,ATAMNA H,KURATSUNE H,et al.Delaying Brain Mitochondrial Decay and Aging with Mitochondrial Antioxidants and Metabolites[J].Annals of the New York Academy of Sciences,2002,959(1):133-166.
• [15]HARDAS S S,RUKHSANA S,CLARK A M,et al.Oxidative modification of lipoic acid by HNE in Alzheimer disease brain☆[J].Redox Biology,2013,1(1):80.
• [16]TABREZ S,JABIR N R,SHAKIL S,et al.A Synopsis on the Role of Tyrosine Hydroxylase in Parkinson's Disease[J].Cns&Neurological Disorders Drug Targets,2012,11(4):152-159.
• [17]李大伟.α-硫辛酸对帕金森病细胞模型保护作用的蛋白质组学研究[D].吉林:吉林大学,2013.
• [18]PARK J,LEE S B,LEE S,et al.Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin[J].Nature,2006,441(7097):1157-1161.
• [19]DIAS V,JUNN E,MOURADIAN M M.The role of oxidative stress in Parkinson's disease[J].Journal of Parkinsons Disease,2013,3(4):461-491.

文章评论(Comment)：