肉苁蓉对帕金森病模型大鼠PI3K、Akt、Bcl-2、Bax蛋白表达的影响
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摘要
目的:观察肉苁蓉对帕金森病(PD)模型大鼠行为学及中脑黑质-纹状体组织PI3K、Akt、Bcl-2、Bax蛋白表达的影响,探讨其对神经细胞的保护作用机制。方法:将48只健康SD雄性大鼠随机分为正常组、溶剂对照组、模型组、肉苁蓉低、中、高剂量组6组,采用颈背部皮下注射鱼藤酮葵花油乳化液建立PD大鼠模型,给予肉苁蓉水煎剂后,第3、7、14天分别进行行为学步幅试验;第14天行为学检测后,处死大鼠,提取黑质-纹状体蛋白,Western Blot检测PI3K、Akt、Bcl-2、Bax蛋白的表达。结果:肉苁蓉干预14天后,与模型组比较,中、高剂量组步幅明显增大(P <0. 01),低、中、高剂量组PI3K、Bcl-2蛋白表达、Bcl-2/Bax值明显升高(P <0. 01或P <0. 05),中剂量组Akt蛋白表达明显升高(P <0. 01),低、中、高剂量组Bax表达明显降低(P <0. 01)。结论:肉苁蓉能改善帕金森病模型大鼠的行为障碍,其对多巴胺神经细胞的保护作用可能是通过影响PI3K/Akt信号通路,上调Bcl-2表达,下调Bax表达,升高Bcl-2/Bax值,进而抑制神经细胞的凋亡实现的。
Objective: To observe the effects of Herba Cistanche on behavior and expression of PI3 K,Akt,Bcl-2 and Bax in substantia nigra and striatum of rats with Parkinson's disease( PD),and to explore the protective mechanism of Herba Cistanche on nerve cells.Methods: 48 healthy male SD rats were randomly divided into 6 groups( normal group,solvent control group,model group,Herba Cistanche low,medium and high dose group),by establishing the rat model of PD subcutaneous injection of rotenone treated sunflower oil emulsion,Herba cistanchis decoction after third,seventh,fourteenth days were toddler behavior a test; fourteenth days after behavioral test,the rats were sacrificed and the extraction of striatal protein expression of PI3 K,Akt,Bcl-2,Bax protein by Western Blot.Results: Cistanche deserticola 14 days,compared with the model group,high dose group stride increased significantly( P < 0. 01),low,medium and high dose groups of PI3 K,Bcl-2,Bcl-2/Bax protein expression increased significantly( P < 0. 01 or P < 0. 05),the middle dose group of Akt protein expression was significantly increased( P < 0. 01),low,medium and high dose group significantly decreased the expression of Bax( P < 0. 01). Conclusion: Cistanche can improve behavior disorder of Parkinson's disease rats and its protective effect on dopaminergic neurons may be through influencing of PI3 K/Akt signaling pathway,upregulate the expression of Bcl-2,expression of Bax,Bcl-2/Bax increased,apoptosis and inhibit nerve cell to achieve.
Objective: To observe the effects of Herba Cistanche on behavior and expression of PI3 K,Akt,Bcl-2 and Bax in substantia nigra and striatum of rats with Parkinson's disease( PD),and to explore the protective mechanism of Herba Cistanche on nerve cells.Methods: 48 healthy male SD rats were randomly divided into 6 groups( normal group,solvent control group,model group,Herba Cistanche low,medium and high dose group),by establishing the rat model of PD subcutaneous injection of rotenone treated sunflower oil emulsion,Herba cistanchis decoction after third,seventh,fourteenth days were toddler behavior a test; fourteenth days after behavioral test,the rats were sacrificed and the extraction of striatal protein expression of PI3 K,Akt,Bcl-2,Bax protein by Western Blot.Results: Cistanche deserticola 14 days,compared with the model group,high dose group stride increased significantly( P < 0. 01),low,medium and high dose groups of PI3 K,Bcl-2,Bcl-2/Bax protein expression increased significantly( P < 0. 01 or P < 0. 05),the middle dose group of Akt protein expression was significantly increased( P < 0. 01),low,medium and high dose group significantly decreased the expression of Bax( P < 0. 01). Conclusion: Cistanche can improve behavior disorder of Parkinson's disease rats and its protective effect on dopaminergic neurons may be through influencing of PI3 K/Akt signaling pathway,upregulate the expression of Bcl-2,expression of Bax,Bcl-2/Bax increased,apoptosis and inhibit nerve cell to achieve.
引文
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[11]Zhang J,Tong W,Sun H,et al. Nrf2-mediated neuroprotection by MANF against 6-OHDA-induced cell damage via PI3K/AKT/GSK3βpathway[J]. Exp Gerontol,2017,100:77-86.
[12]Kim SM,Park YJ,Shin MS,et a. Acacetin inhibits neuronal cell death induced by 6-hydroxydopamine in cellular Parkinson's disease model[J]. Bioorg Med Chem Lett,2017,27(23):5 207-5212.
[13]B D'Orsi,J Mateyka,JH Prehn. Control of mitochondrial physiology and cell death by the Bcl-2 family proteins Bax and Bok[J]. Neurochemistry International,2017,109:162-170.
[14]Ke K,Lou T. MicroRNA-10a suppresses breast cancer progression via PI3K/Akt/m TOR pathway[J]. Oncol Lett,2017,14(5):5 994-6 000.
[15]Yang S S,Qin W,Chen S Y,et al. Effects of cistanche deserticola on behavior and expression of GSK-3βin hippocampus of rat model of parkinson's disease[J]. Rehabilitation Medicine,2016,26(6):24-27+33.
[2]Wang J,Liu H,Zhang X,et al. Sulfated Hetero-Polysaccharides Protect SH-SY5Y Cells from H2O2-Induced Apoptosis by Affecting the PI3K/Akt Signaling Pathway[J]. Mar Drugs,2017,15(4):110.
[3]Chen WF,Wu L,Du ZR,et al. Neuroprotective properties of icariin in MPTP-induced mouse model of Parkinson's disease:Involvement of PI3K/Akt and MEK/ERK signaling pathways[J]. Phytomedicine,2016,25:93-99.
[4]Yal nkaya N,Haytural H,Bilgi B,et al. Expression changes of genes associated with apoptosis and survival processes in Parkinson's disease[J]. Neurosci Lett,2016,615:72-77.
[5]Shaogang,Shuifen,Jinmu,et al. How do Chinese medicines that tonify the kidney inhibit dopaminergic neuron apoptosis[J]. Neural Regeneration Research,2013,8(30):2 820-2 826.
[6]陈忻,张楠,赵晖,等.鱼藤酮致帕金森病大鼠行为学与黑质病理损伤的关系[J].中国神经精神疾病杂志,2008,34(4):232-234.
[7]Chinese Pharmacopoeia Commission. Pharmacopoeia of the People's Republic of China(I)[S]. Beijing:Chemical Industry Press,2015:135.
[8]Zhang K,Ma X,He W,et al. Extracts of Cistanche deserticola Can Antagonize Immunosenescence and Extend Life Span in Senescence-Accelerated Mouse Prone 8(SAM-P8)Mice[J]. Evidencebased Complementary and Alternative Medicine,2014,2014(2):601 383.
[9]林少刚.补肾中药干预MES23. 5多巴胺能神经细胞凋亡的研究[D].福州:福建中医药大学,2012.
[10]Lai Z,Zhang L,Su J,et al. Sevoflurane postconditioning improves long-term learning and memory of neonatal hypoxia-ischemia brain damage rats via the PI3K/Akt-MPTP pathway[J]. Brain Res,2015,1630:25-37.
[11]Zhang J,Tong W,Sun H,et al. Nrf2-mediated neuroprotection by MANF against 6-OHDA-induced cell damage via PI3K/AKT/GSK3βpathway[J]. Exp Gerontol,2017,100:77-86.
[12]Kim SM,Park YJ,Shin MS,et a. Acacetin inhibits neuronal cell death induced by 6-hydroxydopamine in cellular Parkinson's disease model[J]. Bioorg Med Chem Lett,2017,27(23):5 207-5212.
[13]B D'Orsi,J Mateyka,JH Prehn. Control of mitochondrial physiology and cell death by the Bcl-2 family proteins Bax and Bok[J]. Neurochemistry International,2017,109:162-170.
[14]Ke K,Lou T. MicroRNA-10a suppresses breast cancer progression via PI3K/Akt/m TOR pathway[J]. Oncol Lett,2017,14(5):5 994-6 000.
[15]Yang S S,Qin W,Chen S Y,et al. Effects of cistanche deserticola on behavior and expression of GSK-3βin hippocampus of rat model of parkinson's disease[J]. Rehabilitation Medicine,2016,26(6):24-27+33.