首页|龟羚帕安丸对帕金森病大鼠转录因子EB介导自噬调控机制的研究

龟羚帕安丸对帕金森病大鼠转录因子EB介导自噬调控机制的研究

Effect of Guiling Pa'an Pill on the Regulation Mechanism of Transcription Factor EB-mediated Autophagy in Parkinson's Disease Rats

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目的:研究龟羚帕安丸治疗帕金森病(PD)对转录因子EB(TFEB)表达的影响及其机制.方法:将PD大鼠模型随机分为模型组、西药组、中西药组、中药低、中、高剂量组,每组15只,另取15只正常大鼠作为假手术组.模型组及假手术组给予等容积生理盐水,其余组给予相应药物灌胃,各组均连续给药4周.PD大鼠处死后,将中脑黑质组织剥离出来,运用蛋白质印迹法(Western Blotting)检测TFEB、微管相关膜蛋白轻链3 Ⅱ(LC3 Ⅱ)、泛素结合蛋白P62(P62)、酪氨酸羟化酶(TH)、α-突触核蛋白(α-syn)的表达量.结果:与假手术组比较,模型组、西药组、中西药组、中药各剂量组黑质内TFEB、LC3Ⅱ、TH蛋白表达显著降低(P<0.01),P62、α-syn表达显著增高(P<0.01);与模型组比较,西药组、中西药组、中药各剂量组黑质内TFEB、LC3Ⅱ、TH蛋白表达显著增高(P<0.01),P62、α-syn表达显著降低(P<0.01).结论:龟羚帕安丸可通过TFEB激活自噬-溶酶体系统,增强神经细胞自噬活性,增加LC3 Ⅱ、TH表达,促进α-syn、P62降解及清除,发挥神经保护作用.
Objective:To study the effect of Guiling Pa'an Pill on the expression of transcription factor EB(TFEB)in the treat-ment of Parkinson's disease(PD)and its mechanism.Methods:The PD rat model was randomly divided into model group,western medicine group,traditional Chinese and western medicine group and traditional Chinese medicine low,middle and high dose groups,with 15 in each group.Another 15 normal rats were selected as sham operation group.The model group and sham operation group were given same volume of normal saline,and the other groups were given corresponding medicines by intragastric administra-tion for 4 consecutive weeks.After the PD rats were sacrificed,the substantia nigra of the midbrain was collected.The protein ex-pressions of TFEB,microtubule-associated protein light chain 3 Ⅱ(LC3 Ⅱ),P62,tyrosine hydroxylase(TH)and α-synuclein(α-syn)were detected by Western Blotting.Results:Compared with the conditions in sham operation group,the protein expressions of TFEB,LC3 Ⅱ and TH in the substantia nigra of the model group,western medicine group,traditional Chinese and western medicine group and traditional Chinese medicine groups decreased significantly(P<0.01),while the protein expressions of P62 and α-syn increased significantly(P<0.01).Compared with the model group,the western medicine group,traditional Chinese and western medicine group and traditional Chinese medicine groups had up-regulated TFEB,LC3 Ⅱ and TH in substantia nigra(P<0.01),while down-regulated P62 and α-syn(P<0.01).Conclusion:Guiling Pa'an Pill can activate autophagy-lysosome system through TFEB,enhance the autophagy of neural cells,increase LC3 Ⅱ and TH,and promote the degradation and clearance of α-syn and P62,thereby playing a neuroprotective effect.

Parkinson's diseaseGuiling Pa'an PillAutophagyTranscription factor EBMicrotubule-associated protein light chain 3 ⅡP62Tyrosine hydroxylaseα-synuclein

陈帅杰、胡慧慧、常学辉、张良芝、郭健、张创业、王冬莲

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河南中医药大学,郑州,450008

河南中医药大学第二临床医学院,郑州,450002

河南中医药大学中医学院/仲景学院,郑州,450056

帕金森病 龟羚帕安丸 自噬 转录因子EB、微管相关膜蛋白轻链3Ⅱ、泛素结合蛋白P62、酪氨酸羟化酶、α-突触核蛋白

全国名老中医药专家传承工作室建设项目河南省科技攻关计划全国名老中医药专家传承工作室建设项目河南省卫生健康委-国家中医临床研究基地科研专项河南省中医药科学研究专项河南中医药大学研究生科研创新类项目

国中医药人教函[2022]75号222102310630豫卫中医函20223号2021JDZX20652019ZYBJ162021KYCX024

2023

世界中医药
世界中医药学会联合会

世界中医药

CSTPCDCHSSCD北大核心
影响因子:1.266
ISSN:1673-7202
年,卷(期):2023.18(22)
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