摘要
目的:研究葛根素对6-羟多巴胺(6-OHDA)致帕金森病(PD)大鼠黑质组织核转录因子(Nrf2)/抗氧化反应元件(ARE)通路的影响。方法:建立帕金森SD大鼠模型,随机分成5组:模型组、美多巴阳性组(40 mg.kg-1)及葛根素低、中、高剂量组(20,40,80 mg.kg-1)。持续灌胃给药30 d。Elisa法检测黑质组织中γ-谷氨酰半胱氨酸合成酶(γ-GCS)、谷胱甘肽(GSH)、过氧化氢酶(CAT)活性。RT-PCR法检测黑质组织细胞色素c氧化酶(COX)mRNA表达。Western blot法检测转录因子NF-E2相关因子2(Nrf2)、Kelch样环氧氯丙烷相关蛋白-1(Keapl)蛋白表达。结果:与正常组比较,模型组黑质中r-GCS,GSH,CAT活性显著降低,COX mRNA Nrf2,Keapl蛋白表达显著降低(P<0.01);与模型组比较,葛根素有效地增加帕金森病大鼠黑质γ-GCS,GSH,CAT活性(P<0.01)。葛根素低,中,高剂量组能明显上调黑质COX mRNA水平(38.5±4.3)%,(43.2±5.1)%,(57.4±6.2)%(P<0.01),显著增加Nrf2,Keapl蛋白表达(38.5±3.6)%,(52.4±4.8)%,(78.5±7.3)%;(31.7±2.3)%,(40.8±3.5)%,(65.9±6.1)%(P<0.01)。结论:葛根素有效地对抗6-OHDA诱导PD大鼠黑质神经细胞氧化应激性损伤,其机制可能与其调节Nrf2/ARE通路有关。
Objective： To study the effect of puerarin on the Nrf2/ARE pathway in substantia nigra tissue of Parkinson＇s disease （PD） rats model induced by 6-hydroxydopamine （6-OHDA）. Method： SD PD rats model was established, the rats were randomly divided into 5 groups： model group, madopar group （40 mg·kg-1）, low-, medium-and high-dosage groups of puerarin （20, 40, 80 mg·kg-1）.The drugs were intragastrically perfused to rats daily for 30 consecutive days.The activities of γ-glutamylcysteine synthetase （γ-GCS）, glutathione （GSH） and catalase （CAT） in substantia nigra tissue were tested by ELISA method.The expression of cytochrome c oxidase （COX） mRNA was tested by RT-PCR assay.And the nuclear factor E2-related factor 2（Nrf2）, Kelch-like ECH-associated protein 1（Keapl） protein expressions were tested by Western blot analysis. Result： Compared to model group, puerarin effectually elevated the activityof γ-GCS, GSH and CAT in substantia nigra tissue of PD rats （P〈0.01）.And the COX expression at mRNA level in substantia nigra was upregulated （P〈0.01）.The expression of Nrf2 and Keapl proteins was markedly increased. Conclusion： The results reveal that puerarin effectively fight against the oxidative stress damage in nerve cells in substantia nigra of PD rats induced by 6-OHDA, and its probable mechanism may be involved in regulation of Nrf2/ARE pathway.
出处
《中国实验方剂学杂志》
CAS
北大核心
2013年第6期230-233,共4页
Chinese Journal of Experimental Traditional Medical Formulae
