银杏叶提取物对帕金森病模型大鼠脑内神经炎性反应的影响
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摘要
目的观察银杏叶提取物对帕金森病(Parkinson's disease,PD)模型大鼠中脑和纹状体神经炎性反应因子及其调控因子核因子-κB(nuclear factor-kappa B,NF-κB)的影响。方法将32只3月龄雄性SD大鼠采用数字表法随机分为对照组、模型组、低剂量组和高剂量组,每组8只。背部皮下注射鱼藤酮制备PD大鼠模型,低剂量组和高剂量组同时给予银杏叶提取物灌胃共30 d。酶联免疫法检测大鼠脑内纹状体中神经炎性反应因子—肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)及白细胞介素-1β(interleukin-1β,IL-1β)含量变化,同时Western blotting检测大鼠脑内星形胶质细胞、小胶质细胞和NF-κB的表达改变。结果与对照组相比,模型组大鼠纹状体中TNF-α和IL-1β均明显增加(P <0. 01),大鼠脑内GFAP、Iba1和NF-κB表达明显增加(P <0. 05)。银杏叶提取物治疗后明显逆转了上述神经炎性反应,与模型组相比,治疗组GFAP、Iba1和NF-κB蛋白表达明显降低(P <0. 05),大鼠纹状体中TNF-α和IL-1β明显减少(P <0. 05)。同时上述改变有明显剂量依赖性。结论银杏叶提取物能改善PD大鼠脑内的慢性神经炎性反应,保护脑内黑质多巴胺能神经元,为PD的临床治疗提供新的靶点。
Objective Observing the effects of ginkgo biloba extracts on neuroinflammatory factors and their regulatory factors nuclear factor-κB( NF-κB) in the midbrain and striatum of Parkinson's disease( PD) rats. Methods Thirty-two 3-month old male SD rats were randomly divided into control group,model group,low-dose group and high-dose group,and rotenone was injected subcutaneously in the back to prepare PD model. The low-dose group and high-dose group were given ginkgo biloba extracts by gavage for a total of 30 days. The cytokines of tumor necrosis factor-α( TNF-α) and interleukin-1β( IL-1β) were detected by ELISA in the striatum,and the expression of astrocytes,microglia and NF-κB in the striatum were detected by Western blotting. Results Compared with the control group,TNF-αand IL-1β in the striatum of the model group were significantly increased( P < 0. 01),and ginkgo biloba extracts significantly reversed the above neuroinflammatory responses after treatment. The expressions of GFAP,Iba1 and NF-κB in the model group were significantly higher than those in the control group( P < 0. 05),and the expressions of GFAP,Iba1 and NF-κB in ginkgo biloba extracts were significantly lower than those in the model group( P < 0. 05). At the same time,we found that the above changes have significant dose dependence.Conclusion Ginkgo biloba extracts can depress the chronic neuroinflammatory response in the brain of PD rats,protect the dopaminergic neurons,which provides a new target for the clinical treatment of PD.
Objective Observing the effects of ginkgo biloba extracts on neuroinflammatory factors and their regulatory factors nuclear factor-κB( NF-κB) in the midbrain and striatum of Parkinson's disease( PD) rats. Methods Thirty-two 3-month old male SD rats were randomly divided into control group,model group,low-dose group and high-dose group,and rotenone was injected subcutaneously in the back to prepare PD model. The low-dose group and high-dose group were given ginkgo biloba extracts by gavage for a total of 30 days. The cytokines of tumor necrosis factor-α( TNF-α) and interleukin-1β( IL-1β) were detected by ELISA in the striatum,and the expression of astrocytes,microglia and NF-κB in the striatum were detected by Western blotting. Results Compared with the control group,TNF-αand IL-1β in the striatum of the model group were significantly increased( P < 0. 01),and ginkgo biloba extracts significantly reversed the above neuroinflammatory responses after treatment. The expressions of GFAP,Iba1 and NF-κB in the model group were significantly higher than those in the control group( P < 0. 05),and the expressions of GFAP,Iba1 and NF-κB in ginkgo biloba extracts were significantly lower than those in the model group( P < 0. 05). At the same time,we found that the above changes have significant dose dependence.Conclusion Ginkgo biloba extracts can depress the chronic neuroinflammatory response in the brain of PD rats,protect the dopaminergic neurons,which provides a new target for the clinical treatment of PD.
引文
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[12]张辉,马惠清,王晓娟,银杏叶提取物通过激活Nrf2-ARE信号通路对帕金森病大鼠发挥脑保护作用[J],沈阳药科大学学报,2018,35(8):675-679.
[13] Sasaki K,Iwai K. Roles of linear ubiquitinylation,a crucial regulator of NF-κB and cell death,in the immune system[J]. Immunol Rev,2015,266(1):175-189.
[14] Jayasooriya R G P T,Molagoda I M N,Park C,et al. Molecular chemotherapeutic potential of butein:A concise review[J]. Food Chem Toxicol,2018,112:1-10.
[2] Phillipson O T. Management of the aging risk factor for Parkinson's disease[J]. Neurobiol Aging,2014,35(4):847-857.
[3] Taylor J M,Main B S,Crack P J. Neuroinflammation and oxidative stress:co-conspirators in the pathology of Parkinson's disease[J]. Neurochem Int,2013,62,803-819.
[4] Caggiu E,Arru G,Hosseini S,et al. Inflammation,infectious triggers,and Parkinson's disease[J]. Front Neurol,2019,10:122.
[5] Kim B W,Koppula S,Kumar H,et al. Corrigendum to“α-Asarone attenuates microglia-mediated neuroinflammation by inhibiting NF kappa B activation and mitigates MPTP-induced behavioral deficits in a mouse model of Parkinson's disease”[J]. Neuropharmacology,2017,116:444-445.
[6] de Carvalho F O,Felipe F A,de Melo Costa A C,et al.Inflammatory mediators and oxidative stress in animals subjected to smoke inhalation:a systematic review[J]. Lung,2016,194(4):487-499.
[7] Sun T,Wang X,Xu H. Ginkgo biloba extract for angina pectoris:a systematic review[J]. Chin J Integr Med,2015,21(7):542-550.
[8] Lee Y,Lee S,Chang S C,et al. Significant roles of neuroinflammation in Parkinson's disease:therapeutic targets for PD prevention[J]. Arch Pharm Res,2019,4. DOI:10.1007/s12272-019-0113-0.
[9] Pardon M C. Anti-inflammatory potential of thymosinβ4 in the central nervous system:implications for progressive neurodegenerative diseases[J]. Expert Opin Biol Ther,2018,18(supp1):165-169.
[10] Brambilla R. The contribution of astrocytes to the neuroinflammatory response in multiple sclerosis and experimental autoimmune encephalomyelitis[J]. Acta Neuropathol,2019,137(5):757-783.
[11] ChenZ,Zhong D,Li G. The role of microglia in viral encephalitis:a review[J]. J Neuroinflammation,2019,9,16(1):76.
[12]张辉,马惠清,王晓娟,银杏叶提取物通过激活Nrf2-ARE信号通路对帕金森病大鼠发挥脑保护作用[J],沈阳药科大学学报,2018,35(8):675-679.
[13] Sasaki K,Iwai K. Roles of linear ubiquitinylation,a crucial regulator of NF-κB and cell death,in the immune system[J]. Immunol Rev,2015,266(1):175-189.
[14] Jayasooriya R G P T,Molagoda I M N,Park C,et al. Molecular chemotherapeutic potential of butein:A concise review[J]. Food Chem Toxicol,2018,112:1-10.